Browse the corpus

Bibliography Bibliography Jain S, Self WH, Wunderink RG, et al; CDC EPIC Study Team. Community- acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Central Nervous System Infections Med. 2015 37 3 :4lS 27 . [PMID: 26t7 2429] doi: 10' 1056 / N EJMoa1500245 r Hasbun R. Update and advances in community acquired bacterial meningitis. Kamat IS. Ramachandran V Eswaran H, et al. Procalcitonin to distinguish viral Curr Opin Infect Dis. 2Ol9;32:233-238. [PMID: 31021955] doi:10.1097/ from bacterial pneumonia: A systematic review and meta-analysis. Clin QCO.0000000000000s43 Infect Dis. 2020 ;70 538 - 542. [PMID : 3l24ll4}) doi: 10. 1093 /cid I ciz! 45 : Charlier C, Perrodeau E, Leclercq A, et al; MONALISA study group. Clinical Mandell LA, Niederman MS. Aspiration pneumonia. N Engl I Med. 2019; features and prognostic factors of listeriosis: the MONALISA national pro- 380 651 663. IPMID: 307 6319 6) doi: 10. 1056 / NEJMral714562 :

Charlier C, Perrodeau E, Leclercq A, et al; MONALISA study group. Clinical Mandell LA, Niederman MS. Aspiration pneumonia. N Engl I Med. 2019; features and prognostic factors of listeriosis: the MONALISA national pro- 380 651 663. IPMID: 307 6319 6) doi: 10. 1056 / NEJMral714562 : spective cohort study. Lancet Infect Dis. 2017;17:510-519. [PMID: 28139$2) Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with doi:10.1016/S147 3 -3099 (t6) SOSZT Z community acquired pneumonia. an official clinical practice guideline of Hansen MA, Samannodi MS, Castelblanco RL, et al. Clinical epidemiolory, risk the American Thoracic Society and Infectious Diseases Society of America. factors, and outcomes of encephalitis in older adults. Clin Infect Dis. Am J Respir Crit Care Med. 2079 ;2OO :e4S e67. [PMID : 31573350] doi:lO.116 4 I 2o2O ;7 O :2377 2385. [PMI D : 3t29 4449) doi 10. 1093 /c id I ciz635 : rccm.201908-1581ST Hasbun R, Rosenthal N, Balada Llasat JM, et al. Epidemiologr of meningitis Uranga A, Espafla PB Bilbao A, et al. Duration of antibiotic treatment in and encephalitis in the United States, 2011-2014. Clin Infect Dis. 2017; community-acquired pneumonia: A multicenter randomized clinical trial. 65:359 363. [PMID: 28419350] doi:10.1093/cid/cix319 JAMA Intern Med. 2016 17 6 :1257 - 65. [PMID, 27 4551661 doi: 10. 1001 /jamain ;

Hasbun R, Rosenthal N, Balada Llasat JM, et al. Epidemiologr of meningitis Uranga A, Espafla PB Bilbao A, et al. Duration of antibiotic treatment in and encephalitis in the United States, 2011-2014. Clin Infect Dis. 2017; community-acquired pneumonia: A multicenter randomized clinical trial. 65:359 363. [PMID: 28419350] doi:10.1093/cid/cix319 JAMA Intern Med. 2016 17 6 :1257 - 65. [PMID, 27 4551661 doi: 10. 1001 /jamain ; ternmed.2016.3633 Lopez A, Lee A, Guo A, et al. Vital signs: surveillance for acute flaccid myelitis Vaughn VM, Flanders SA, Snyder A, et al. Excess antibiotic treatment duration United States, 2018. MMWR Morb Mortal Wkly Rep. 2019;68:608-614. and adverse events in patients hospitalized with pneumonia: A multihos- [ptvttO, 31295n21 doi:10. 15585/mmwr.mm6827el pital cohort study. Ann Intern Med. 20i9;171:i53-163. [PMID: 31284301] McGill Fl, Heyderman RS, Michael BD, et al. The UK joint specialist societies doi:10.7326lM18 3640 guideline on the diagnosis and management of acute meningitis and Wunderink RG, Waterer G. Advances in the causes and management of com- meningococcal sepsis in immunocompetent adults. i Infect. 2016;72:405- 38. [PMID : 2684s731] doi 10. 1016 /j. jinf. 2016. 01. 007 : munity acquired pneumonia in adults. BMJ. 2017;358:j2471. [ptvllO' 28 69 42st) doi : 1 0. 113 6 /b mi.i247 7 Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventriculi Tick-Borne Diseases tis and meningitis. Clin Infect Dis. 2017;64:e34-e65. [PMIO, 28203777) Baker Pl. Is it possible to make a correct diagnosis of lyme disease on symp- doi:10.1093 /cid/ciw861 toms alone? Review of key issues and public health implications. Am J Med. van de Beek D, Cabellos C, Dzupova O, et al; ESCMID Study Group for 2OI9;732:r748 1152. [PMID: 31028718] doi:10.1016/j.amjmed.2019.04.001 Infections of the Brain (ESGIB). ESCMID guideline: diagnosis and treat- Berende A, ter Hofstede HJ, Vos FJ, et al. Randomized trial of longer term ment of acute bacterial meningitis. Clin Microbiol Infect. 2016;22 Suppl therapy for symptoms attributed to lyme disease. N Engl J Med. 2016; 3 :S37 62. [pl,tIO, 27 O 620971 doi: 10. 1016 /j. cmi. 2016. 01. 007 37 4 :t209 20. I PMID: 27 028971) doi:10. 1056 /NEJMoa1505425

tr Item 1 A 63-year-old woman is evaluated in the emergency On physical examination, temperature is 39.1 .C (tOZ.+ "F), blood pressure is L36172 mm Hg, pulse rate is 110/min, and respiration rate is 2Olmin. Oxygen saturation Ut Ul q, l,I tt department for fever and chills of 1 day's duration. She has been receiving intravenous penicillin for 2 weeks at home is 92% breathing ambient air. Breath sounds are decreased a through a peripherally inserted central catheter (plCC) for at the lung bases bilaterally. =(l, r/I group B streptococcal osteomyelitis of the right great toe. A chest radiograph shows bilateral interstitial infll- Medical history is also notable for diabetes mellitus treated trates. with metformin. On physical examination, temperature is 38.8 .C Which of the following is the most likely cause of this (tOt.g'F); the remainder of the vital signs are norrnal. Ten- patient's symptoms? derness is noted at the right brachial PICC insertion site, (A) Avian influenza A H7N9 without erythema or drainage. The right great toe wound is healed. (B) Chlamydiapsittaci l^aboratory studies show a leukoclte count of lT,4OOlltL (C) Coxiellaburnetii Ol.qxrcs lL).iwo sets of peripherally drawn blood cultures (D) Hanta virus grow gram-negative rods. (E) Rhodococcus equi Which of the following is the most appropriate management? (A) Maintain PICC; switch to daptomycin Item 4 A 66-year-old woman is evaluated for increasing oxygen tr requirements over the past 18 hours. She developed hyper- (B) Maintain PICC; switch to meropenem capnic respiratory failure requiring intubation 7 days ago (C) Remove PICC; continue intravenous penicillin, following a colectomy for colon cancer. Suctioned spu- peripherally administered tum has become thicker. Medical history is signiflcant for (D) Remove PICC, switch to intravenous cefepime, moderately severe COPD and right leg cellulitis, which peripherally administered was treated with cefazolin 1 month ago. Medications are albuterol, tiotropium bromide, and salmeterol-fluticasone inhalers. Item 2 On physical examination, temperature is 38.4 "C (tOt.t'F); othervital signs are normal. Oxygen saturation is A 21*year-old man is concerned about a sexually transmit- 90% on an Fio, of 0.6 and positive end*expiratory pressure ted infection. Six weeks ago, he had unprotected sexual of 10 cm HrO. Pulmonary examination reveals scattered encounters (oral and vaginal sex) with a new female part- right-sided rhonchi. ner. He reports no symptoms. He takes no medications. Laboratory studies show a leukocyte count of 17,2OOl1tL On physical examination, vital signs are norrnal. No (fi.zxloe/L). lymphadenopathy or pharyngeal erythema or exudate is Chest radiograph shows right lower lobe and right noted. No genital lesions or other rashes are present. middle lobe inflltrates. Nucleic acid amplification testing (NAAT) of a pharyn- geal swab is positive for Neisseria gonorrhoe ae andnegative for Chlamydiatrachomatis. NAAT of a urine sample is neg- Which of the following is the most appropriate treatment? ative for chlamydia and gonorrhea. HIV testing and syphilis (A) Ceftazidime and vancomycin serology are negative. (B) Ceftazidime, ciprofloxacin, andvancomycin (C) Ertapenem Which of the following is the most appropriate treatment? (D) Piperacillin-tazobactam and vancomycin (A) Ceflxime (B) Ceftriaxone (C) Ceftriaxone and azithromycin Item 5 (D) Ceftriaxone and doxycycline A 42-year-old man with HIV infection seeks advice (E) Cefuroxime regarding HIV transmission risk. He is in a commit- ted, monogamous relationship, and his husband is HIV negative (conflrmed by fourth generation HIV testing 2 days ago). His HIV infection has been well-controlled for Item 3 10 years. His only medication is a flxed, co-formulated A S9-year-old man is hospitalized with a S-day history of regimen of tenofovir alafenamide, emtricitabine, and nonproductive cough and fever. He recreationally breeds bictegravir once daily. carrier pigeons. He reports no travel outside of the United Laboratory studies l week ago showed an undetectable States. Medical history is noncontributory, and he takes no HIV-1 quantitative RNA, which remains the same from medications. 6 months and 1 year ago. The last CD4 cell count was 650/pL.

through a peripherally inserted central catheter (plCC) for at the lung bases bilaterally. =(l, r/I group B streptococcal osteomyelitis of the right great toe. A chest radiograph shows bilateral interstitial infll- Medical history is also notable for diabetes mellitus treated trates. with metformin. On physical examination, temperature is 38.8 .C Which of the following is the most likely cause of this (tOt.g'F); the remainder of the vital signs are norrnal. Ten- patient's symptoms? derness is noted at the right brachial PICC insertion site, (A) Avian influenza A H7N9 without erythema or drainage. The right great toe wound is healed. (B) Chlamydiapsittaci l^aboratory studies show a leukoclte count of lT,4OOlltL (C) Coxiellaburnetii Ol.qxrcs lL).iwo sets of peripherally drawn blood cultures (D) Hanta virus grow gram-negative rods. (E) Rhodococcus equi Which of the following is the most appropriate management? (A) Maintain PICC; switch to daptomycin Item 4 A 66-year-old woman is evaluated for increasing oxygen tr requirements over the past 18 hours. She developed hyper- (B) Maintain PICC; switch to meropenem capnic respiratory failure requiring intubation 7 days ago (C) Remove PICC; continue intravenous penicillin, following a colectomy for colon cancer. Suctioned spu- peripherally administered tum has become thicker. Medical history is signiflcant for (D) Remove PICC, switch to intravenous cefepime, moderately severe COPD and right leg cellulitis, which peripherally administered was treated with cefazolin 1 month ago. Medications are albuterol, tiotropium bromide, and salmeterol-fluticasone inhalers. Item 2 On physical examination, temperature is 38.4 "C (tOt.t'F); othervital signs are normal. Oxygen saturation is A 21*year-old man is concerned about a sexually transmit- 90% on an Fio, of 0.6 and positive end*expiratory pressure ted infection. Six weeks ago, he had unprotected sexual of 10 cm HrO. Pulmonary examination reveals scattered encounters (oral and vaginal sex) with a new female part- right-sided rhonchi. ner. He reports no symptoms. He takes no medications. Laboratory studies show a leukocyte count of 17,2OOl1tL On physical examination, vital signs are norrnal. No (fi.zxloe/L). lymphadenopathy or pharyngeal erythema or exudate is Chest radiograph shows right lower lobe and right noted. No genital lesions or other rashes are present. middle lobe inflltrates. Nucleic acid amplification testing (NAAT) of a pharyn- geal swab is positive for Neisseria gonorrhoe ae andnegative for Chlamydiatrachomatis. NAAT of a urine sample is neg- Which of the following is the most appropriate treatment? ative for chlamydia and gonorrhea. HIV testing and syphilis (A) Ceftazidime and vancomycin serology are negative. (B) Ceftazidime, ciprofloxacin, andvancomycin (C) Ertapenem Which of the following is the most appropriate treatment? (D) Piperacillin-tazobactam and vancomycin (A) Ceflxime (B) Ceftriaxone (C) Ceftriaxone and azithromycin Item 5 (D) Ceftriaxone and doxycycline A 42-year-old man with HIV infection seeks advice (E) Cefuroxime regarding HIV transmission risk. He is in a commit- ted, monogamous relationship, and his husband is HIV negative (conflrmed by fourth generation HIV testing 2 days ago). His HIV infection has been well-controlled for Item 3 10 years. His only medication is a flxed, co-formulated A S9-year-old man is hospitalized with a S-day history of regimen of tenofovir alafenamide, emtricitabine, and nonproductive cough and fever. He recreationally breeds bictegravir once daily. carrier pigeons. He reports no travel outside of the United Laboratory studies l week ago showed an undetectable States. Medical history is noncontributory, and he takes no HIV-1 quantitative RNA, which remains the same from medications. 6 months and 1 year ago. The last CD4 cell count was 650/pL. 113

Self-Assessment Test tl .D -D rh Which of the following is the most appropriate Item 8 UI t management to prevent HIV transmission? A72-year-old man is evaluated for a fever. He was hospital- EI UI .D (A) Consistent condom use with each episode of sex ized, 3 days ago for lower gastrointestinal bleeding. He has UT ur no other medical problems and takes no medications. - (B) Daily HIV pre-exposure prophylaxis for the partner J (D On physical examination, temperature is 38.4 'C J (C) On-demand HIV pre exposure prophylaxis for the (tOr.t 'F); other vital signs are normal. An inflamed periph- -t partner -l eral venous catheter site is discovered. The remainder of the o UI (D) No additional preventive strategy necessary examination is normal. -t The venous catheter is removed, blood cultures are obtained. and empiric vancomycin is initiated. Item 6 Initial blood cultures grow methicillin-sensitive Staph- A 28-year-old woman is evaluated for fatigue. Six months ylococcus aureus at 48 hours; repeat cultures are pending. ago, she developed erythema migrans and was diagnosed The patient is afebrile. with early localized Lyme disease. No serologic testing No valvular vegetations are seen on a transthoracic was performed. She was treated with a 10-day course echocardiogram. of doxycycline. The skin lesion resolved, but she contin- ues to experience malaise, myalgia, poor concentration, Which of the following is the most appropriate and disabling fatigue. She reports no fevers. Medical management? history is otherwise noncontributory, and she takes no (A) Add rifampin medications. On physical examination, vital signs and the remainder (B) Continuevancomycin of the examination are normal. (C) Switch to cefazolin Laboratory studies, including a complete blood count (D) Transesophageal echocardiography with differential, metabolic proflle, and thyroid function tests, are normal. Item 9 Which of the following is the most appropriate management? A 28-year-old woman is hospitalized with a S-day history of chest pain, fever, and cough with green sputum. Two (A) Doxycycline for an additional 14 days weeks ago, she developed an influenza-like illness and (B) Lumbar puncture seemed to improve before the onset of the most recent (C) Lyme serologic testing symptoms. She has no other medical conditions and takes (D) Reassurance and serial follow-up no medications. On physical examination, temperature is 38.6 'C (tot.s "F), blood pressure is 150/90 mm Hg, pulse rate is ll2lmin, and respiration rate is 28/min. Oxygen saturation tr Item 7 A 24-year-old man is hospitalized with a 1-day history is 96% breathing ambient air. Crackles are heard at the right lower lung base on pulmonary auscultation. The remainder of fever. He resides at a skilled nursing facility; he was in of the physical examination is normal. a motor vehicle accident 6 months ago and sustained a Blood and sputum cultures are obtained. COVID-19 traumatic brain injury. He is totally dependent on others testing is negative. for care. He is fed through a percutaneous gastrostomy Chest radiograph shows a right lower lobe inflltrate. tube. Three days ago, he had an episode of emesis, and Empiric therapy for community-acquired pneumo- tube feed material r,r,as suctioned from his oropharynx. nia is initiated with ceftriaxone, azithromycin, and van- He experiences anaphylaxis with penicillin; he takes no comycin. medications. Ceftriaxone and azithromycin are discontinued on hos- On physical examination, temperature is 38.4 "C pital day 2 when blood and sputum cultures return positive (tOt.t 'F), blood pressure is 110/70 mm Hg, pulse rate is for methicillin-resist ant Stapkglococcus aureuswith a van- 96/min, and respiration rate is 20imin. Oxygen saturation is comycin minimum inhibitory concentration of (0.5 pg/ml. 9 2"/,, br eathing ambient air. She remains febrile, but repeat blood and sputum cultures Sputum Gram stain shows moderate polymorphonu- show no growth. Her temperature on hospital day 5 remains clear cells but no bacteria. COVID-19 testing is negative. elevated at 39.2"C (102.6'F). A chest radiograph shows right lower lobe consoli- A repeat chest radiograph shows a right-sided pleural dation. effusion. A subsequent CT scan is shown on the next page.

tl .D -D rh Which of the following is the most appropriate Item 8 UI t management to prevent HIV transmission? A72-year-old man is evaluated for a fever. He was hospital- EI UI .D (A) Consistent condom use with each episode of sex ized, 3 days ago for lower gastrointestinal bleeding. He has UT ur no other medical problems and takes no medications. - (B) Daily HIV pre-exposure prophylaxis for the partner J (D On physical examination, temperature is 38.4 'C J (C) On-demand HIV pre exposure prophylaxis for the (tOr.t 'F); other vital signs are normal. An inflamed periph- -t partner -l eral venous catheter site is discovered. The remainder of the o UI (D) No additional preventive strategy necessary examination is normal. -t The venous catheter is removed, blood cultures are obtained. and empiric vancomycin is initiated. Item 6 Initial blood cultures grow methicillin-sensitive Staph- A 28-year-old woman is evaluated for fatigue. Six months ylococcus aureus at 48 hours; repeat cultures are pending. ago, she developed erythema migrans and was diagnosed The patient is afebrile. with early localized Lyme disease. No serologic testing No valvular vegetations are seen on a transthoracic was performed. She was treated with a 10-day course echocardiogram. of doxycycline. The skin lesion resolved, but she contin- ues to experience malaise, myalgia, poor concentration, Which of the following is the most appropriate and disabling fatigue. She reports no fevers. Medical management? history is otherwise noncontributory, and she takes no (A) Add rifampin medications. On physical examination, vital signs and the remainder (B) Continuevancomycin of the examination are normal. (C) Switch to cefazolin Laboratory studies, including a complete blood count (D) Transesophageal echocardiography with differential, metabolic proflle, and thyroid function tests, are normal. Item 9 Which of the following is the most appropriate management? A 28-year-old woman is hospitalized with a S-day history of chest pain, fever, and cough with green sputum. Two (A) Doxycycline for an additional 14 days weeks ago, she developed an influenza-like illness and (B) Lumbar puncture seemed to improve before the onset of the most recent (C) Lyme serologic testing symptoms. She has no other medical conditions and takes (D) Reassurance and serial follow-up no medications. On physical examination, temperature is 38.6 'C (tot.s "F), blood pressure is 150/90 mm Hg, pulse rate is ll2lmin, and respiration rate is 28/min. Oxygen saturation tr Item 7 A 24-year-old man is hospitalized with a 1-day history is 96% breathing ambient air. Crackles are heard at the right lower lung base on pulmonary auscultation. The remainder of fever. He resides at a skilled nursing facility; he was in of the physical examination is normal. a motor vehicle accident 6 months ago and sustained a Blood and sputum cultures are obtained. COVID-19 traumatic brain injury. He is totally dependent on others testing is negative. for care. He is fed through a percutaneous gastrostomy Chest radiograph shows a right lower lobe inflltrate. tube. Three days ago, he had an episode of emesis, and Empiric therapy for community-acquired pneumo- tube feed material r,r,as suctioned from his oropharynx. nia is initiated with ceftriaxone, azithromycin, and van- He experiences anaphylaxis with penicillin; he takes no comycin. medications. Ceftriaxone and azithromycin are discontinued on hos- On physical examination, temperature is 38.4 "C pital day 2 when blood and sputum cultures return positive (tOt.t 'F), blood pressure is 110/70 mm Hg, pulse rate is for methicillin-resist ant Stapkglococcus aureuswith a van- 96/min, and respiration rate is 20imin. Oxygen saturation is comycin minimum inhibitory concentration of (0.5 pg/ml. 9 2"/,, br eathing ambient air. She remains febrile, but repeat blood and sputum cultures Sputum Gram stain shows moderate polymorphonu- show no growth. Her temperature on hospital day 5 remains clear cells but no bacteria. COVID-19 testing is negative. elevated at 39.2"C (102.6'F). A chest radiograph shows right lower lobe consoli- A repeat chest radiograph shows a right-sided pleural dation. effusion. A subsequent CT scan is shown on the next page. Which of the following is the most appropriate treatment? Which of the following is the most appropriate (A) Aztreonam and metronidazole management? (B) Ceftriaxone and azithromycin (A) Add cefepime (C) Levofloxacin (B) Add gentamicin (D) Meropenem (C) Perform bronchoscopy with transbronchial biopsy (E) Moxifloxacin and clindamycin (D) Perform thoracentesis and drainage

Which of the following is the most appropriate treatment? Which of the following is the most appropriate (A) Aztreonam and metronidazole management? (B) Ceftriaxone and azithromycin (A) Add cefepime (C) Levofloxacin (B) Add gentamicin (D) Meropenem (C) Perform bronchoscopy with transbronchial biopsy (E) Moxifloxacin and clindamycin (D) Perform thoracentesis and drainage 114

Self-Assessment Test *. vt (C) Stop current antibiotics; start ceftriaxone F G, *t (D) Stop current antibiotics; start levofloxacin ? o, (E) Continue current regimen tr yt UI c, Ut Item 12 t A 26-year-old woman is seen for follow-up discussion of r- a test results. Three days ago, she was evaluated for a l-week -?Jl €,

*. vt (C) Stop current antibiotics; start ceftriaxone F G, *t (D) Stop current antibiotics; start levofloxacin ? o, (E) Continue current regimen tr yt UI c, Ut Item 12 t A 26-year-old woman is seen for follow-up discussion of r- a test results. Three days ago, she was evaluated for a l-week -?Jl €, history of a nonpruritic rash that appears to be resolving since the initial evaluation. The patient reports no recent history of oral or genital ulcers. She is transgender. She has multiple sexual partners (men and women) and reports consistent use of condoms except for oral sex. Medical his- tory is notable for two instances of gonorrhea and treatment for early latent syphilis l year ago. Medications are combina- tion tenofovir-emtricitabine. ITEM 9 On physical examination, temperature is 37.9 oC (1OO.Z "F); other vital signs are norrnal. Enlarged cervical,

history of a nonpruritic rash that appears to be resolving since the initial evaluation. The patient reports no recent history of oral or genital ulcers. She is transgender. She has multiple sexual partners (men and women) and reports consistent use of condoms except for oral sex. Medical his- tory is notable for two instances of gonorrhea and treatment for early latent syphilis l year ago. Medications are combina- tion tenofovir-emtricitabine. ITEM 9 On physical examination, temperature is 37.9 oC (1OO.Z "F); other vital signs are norrnal. Enlarged cervical, tr Item 1O A S3-year-old woman is evaluated in the emergency depart- axillary, and epitrochlear lymph nodes are present. Faint, erythematous macules andpapules are spreadoverthe trunk and extremities; a few lesions are noted on the Ieft palm. ment for a 2-day history of watery diarrhea occurring 5 times Rapid plasma reagin (RPR) is 1:128; RPR 3 months ago daily. She recently had community-acquired pneumonia was 1:2. Testing of urine and throat and anal swabs for gon- treated with levofloxacin 1 week ago. She takes no medications. orrhea and chlamydia is negative. HIV testing is negative. On physical examination, temperature is 37.6 "C (gg.Z "F); other vital signs are normal. On abdominal exam- Which of the following is the most appropriate treatment? ination, bowel sounds are present with diffuse tenderness to palpation but no distension or guarding. (A) Benzathine penicillin, intramuscularly (single dose) Laboratory studies show a leukocyte count of 12,000/pL (B) Benzathine penicillin, intramuscularly (weekly for (tZ x 10e/L) and a serum creatinine level of 1.1 mg/dl three doses) (eZ.Z pmolll). Stool testing for Clostridioides dfficile is (C) Ceftriaxone, intramuscularly (single dose) positive. (D) Doxycycline, orally (forl4 days) Which of the following is the most appropriate treatment? (A) Fecal microbiota transplant (B) Intravenousvancomycin Item 13 A S5-year-old man is hospitalized for necrotizing fasciitis tr (C) Oral metronidazole following a foot laceration on a seashell 2 days ago while (D) Oral vancomycin wading in the Gulf of Mexico. Medical history is notable for cirrhosis secondary to alcohol use. He takes no medications. (E) Oral vancomycin plus intravenous metronidazole On physical examination, temperature is 39.1 'C OOZ.q "F), blood pressure is 96156 mm Hg, pulse rate is

tr Item 1O A S3-year-old woman is evaluated in the emergency depart- axillary, and epitrochlear lymph nodes are present. Faint, erythematous macules andpapules are spreadoverthe trunk and extremities; a few lesions are noted on the Ieft palm. ment for a 2-day history of watery diarrhea occurring 5 times Rapid plasma reagin (RPR) is 1:128; RPR 3 months ago daily. She recently had community-acquired pneumonia was 1:2. Testing of urine and throat and anal swabs for gon- treated with levofloxacin 1 week ago. She takes no medications. orrhea and chlamydia is negative. HIV testing is negative. On physical examination, temperature is 37.6 "C (gg.Z "F); other vital signs are normal. On abdominal exam- Which of the following is the most appropriate treatment? ination, bowel sounds are present with diffuse tenderness to palpation but no distension or guarding. (A) Benzathine penicillin, intramuscularly (single dose) Laboratory studies show a leukocyte count of 12,000/pL (B) Benzathine penicillin, intramuscularly (weekly for (tZ x 10e/L) and a serum creatinine level of 1.1 mg/dl three doses) (eZ.Z pmolll). Stool testing for Clostridioides dfficile is (C) Ceftriaxone, intramuscularly (single dose) positive. (D) Doxycycline, orally (forl4 days) Which of the following is the most appropriate treatment? (A) Fecal microbiota transplant (B) Intravenousvancomycin Item 13 A S5-year-old man is hospitalized for necrotizing fasciitis tr (C) Oral metronidazole following a foot laceration on a seashell 2 days ago while (D) Oral vancomycin wading in the Gulf of Mexico. Medical history is notable for cirrhosis secondary to alcohol use. He takes no medications. (E) Oral vancomycin plus intravenous metronidazole On physical examination, temperature is 39.1 'C OOZ.q "F), blood pressure is 96156 mm Hg, pulse rate is tr Item 11 A 65-year-old man is evaluated 3 days after hospitalization 100/min, and respiration rate is 23/min. The right foot and leg up to the level of the knee are very tender, edematous, and covered with scattered hemorrhagic bullae. and admission to the ICU with multilobar pneumonia and Empiric vancomycin and imipenem are administered. respiratory failure. He was intubated, vasopressors were Emergent surgical debridement is performed, which con- started, and empiric antimicrobial therapy was initiated. flrms a diagnosis of necrotizing fasciitis with intraoperative Today, his fever has resolved, vasopressors are discontin* cultures revealing Vibrio uulnificus 24 hours later. ued, and he is extubated. He is transferred to a hospital bed outside of the ICU. Two months ago, he was admitted to the Which of the following is the most appropriate antibiotic ICU for pneumonia with negative sputum cultures. Medica- treatment? tions are vancomycin, cefepime, and azithromycin. On physical examination, vital signs are norrnal. The (A) Doxycycline plus ceftazidime examination is unremarkable. (B) Nafcillin plus rifampin Sputum and blood cultures and a urine Legionella (C) Penicillin plus clindamycin antigen test are negative. (D) Vancomycin plus clindamycin Which of the following is the most appropriate treatment at this time? Item 14 (A) Continue cefepime and azithromycin; stopvancomycin A23-year-old woman undergoes follow-up after treatment (B) Continue vancomycin and cefepime; stop azithromycin for gonococcal arthritis; she was treated with ceftriaxone.

tr Item 11 A 65-year-old man is evaluated 3 days after hospitalization 100/min, and respiration rate is 23/min. The right foot and leg up to the level of the knee are very tender, edematous, and covered with scattered hemorrhagic bullae. and admission to the ICU with multilobar pneumonia and Empiric vancomycin and imipenem are administered. respiratory failure. He was intubated, vasopressors were Emergent surgical debridement is performed, which con- started, and empiric antimicrobial therapy was initiated. flrms a diagnosis of necrotizing fasciitis with intraoperative Today, his fever has resolved, vasopressors are discontin* cultures revealing Vibrio uulnificus 24 hours later. ued, and he is extubated. He is transferred to a hospital bed outside of the ICU. Two months ago, he was admitted to the Which of the following is the most appropriate antibiotic ICU for pneumonia with negative sputum cultures. Medica- treatment? tions are vancomycin, cefepime, and azithromycin. On physical examination, vital signs are norrnal. The (A) Doxycycline plus ceftazidime examination is unremarkable. (B) Nafcillin plus rifampin Sputum and blood cultures and a urine Legionella (C) Penicillin plus clindamycin antigen test are negative. (D) Vancomycin plus clindamycin Which of the following is the most appropriate treatment at this time? Item 14 (A) Continue cefepime and azithromycin; stopvancomycin A23-year-old woman undergoes follow-up after treatment (B) Continue vancomycin and cefepime; stop azithromycin for gonococcal arthritis; she was treated with ceftriaxone. 115

Self-Assessment Test lrl o --h I Her sister had meningococcal meningitis 2 years ago. The Item 1 7 D ur patient takes no medications. A 27 -year-old woman is hospitalized with a 2-day history of gr .D On physical examination, she feels well with complete bloody diarrhea associated with abdominal cramping. She UI UI resolution of symptoms. Vital signs are normal, and the attended a picnic 5 days ago and swam in an adjacent lake. J examination is unremarkable. She reports no fever. Medical history is otherwise unre- o J markable, and she takes no medications. { 1-l.

lrl o --h I Her sister had meningococcal meningitis 2 years ago. The Item 1 7 D ur patient takes no medications. A 27 -year-old woman is hospitalized with a 2-day history of gr .D On physical examination, she feels well with complete bloody diarrhea associated with abdominal cramping. She UI UI resolution of symptoms. Vital signs are normal, and the attended a picnic 5 days ago and swam in an adjacent lake. J examination is unremarkable. She reports no fever. Medical history is otherwise unre- o J markable, and she takes no medications. { 1-l. .D Which of the following is the most appropriate screening On physical examination, temperature is 37 "C (98.6 "F), test to perform next? blood pressure is12Ol70 mm Hg, and pulse rate is 105/min. * Ut On abdominal examination, bowel sounds are present with (A) CD4lymphocytesubset diffuse tenderness to palpation but no guarding. (B) Serum IgA level Laboratory studies: (C) Total hemolytic complement (CHro) level Hematocrit 27% (D) No additional testing Leukocyte count 16,000/pL (16 x 10e/L) Platelet count 25,000/pL (zs x roe/L) Creatinine 2.7 mgldL (zeq pmol/L) Item 1 5 A peripheral blood smear is shown. A 38-year-old man is re-evaluated for a 3-month history of nonproductive cough, myalgia, arthralgia, malaise, fatigue, night sweats, and fever. He was previously well, has not travelled, and takes no medications. He lives in southern l

.D Which of the following is the most appropriate screening On physical examination, temperature is 37 "C (98.6 "F), test to perform next? blood pressure is12Ol70 mm Hg, and pulse rate is 105/min. * Ut On abdominal examination, bowel sounds are present with (A) CD4lymphocytesubset diffuse tenderness to palpation but no guarding. (B) Serum IgA level Laboratory studies: (C) Total hemolytic complement (CHro) level Hematocrit 27% (D) No additional testing Leukocyte count 16,000/pL (16 x 10e/L) Platelet count 25,000/pL (zs x roe/L) Creatinine 2.7 mgldL (zeq pmol/L) Item 1 5 A peripheral blood smear is shown. A 38-year-old man is re-evaluated for a 3-month history of nonproductive cough, myalgia, arthralgia, malaise, fatigue, night sweats, and fever. He was previously well, has not travelled, and takes no medications. He lives in southern l .r*:: I , I Ohio and works as an organic farmer. ',w*" .-:i, !: li On physical examination, temperature is 38.5 "C il ,r,: I

I Ohio and works as an organic farmer. ',w*" .-:i, !: li On physical examination, temperature is 38.5 "C il ,r,: I * (rOf.g "F); other vital signs are normal. Scattered crackles # are heard bilaterally on pulmonary auscultation. Laboratory studies show a hemoglobin level of 12.5 gldL Ozs gL) and leukocyte count of 74,400l1t"L (14.4 x 10e/L). An HIV antigen/antibody combination assay is negative. i .$i Chest radiograph shows a right middle lobe inflltrate with hilar lymphadenopathy and a carinal mass. ffi ii. fl., t ,l Sputum shows many round, budding yeast with a broad base.

* (rOf.g "F); other vital signs are normal. Scattered crackles # are heard bilaterally on pulmonary auscultation. Laboratory studies show a hemoglobin level of 12.5 gldL Ozs gL) and leukocyte count of 74,400l1t"L (14.4 x 10e/L). An HIV antigen/antibody combination assay is negative. i .$i Chest radiograph shows a right middle lobe inflltrate with hilar lymphadenopathy and a carinal mass. ffi ii. fl., t ,l Sputum shows many round, budding yeast with a broad base. Which of the following is the most likely diagnosis? @ .,rrr + (A) Blastomycosis (B) Candidiasis Which of the following infections is the most likely cause (C) Coccidioidomycosis of this patient's illness? (D) Mucormycosis (A) Cyclospora (B) Escherichia coli Item 1 6 (C) Giardia A 3S-year-old man is evaluated in late August for right facial (D) Norovirus nerve palsy of 2 days' duration. His initial evaluation in the emergency department included Lyme serology. Treatment was deferred pending test results. He is a landscaper in Rhode Island. Other medical history is unremarkable, and Item 18 A 62-year old man is evaluated for a fever. An indwelling tr he takes no medications. urinary catheter rvas inserted during coronary artery b1'pass On physical examination, vital signs are normal. He surgery 12 hours ago. Nurses obtained a urinalysis. has right-sided peripheral seventh cranial nerve palsy. The On physical examination. temperature is 38.1 oC remainder of his neurologic examination is normal. No rash (100.6 "F): the remainder of the vital signs and ph-v-sical is present. examination are noncontributory. The urinary catheter is Enzyme immunoassay is positive for Borreliaburgdor- removed. feri. B. burgdorferi IgM Western blot is also positive, and IgG Urinall,'sis sholt s 20 leukocytes, hpf. Western blot is negative. Whieh of the fbllowing is the most appropriate Which of the following is the most appropriate management? management? (A) Perform lumbar puncture (A) Obtain urine culture (B) Prescribe doxycycline (B) Repeat urinalysis (C) Prescribeprednisone (C) Start empiric antibiotics (D) Start parenteral ceftriaxone (D) Clinical observation

Which of the following is the most likely diagnosis? @ .,rrr + (A) Blastomycosis (B) Candidiasis Which of the following infections is the most likely cause (C) Coccidioidomycosis of this patient's illness? (D) Mucormycosis (A) Cyclospora (B) Escherichia coli Item 1 6 (C) Giardia A 3S-year-old man is evaluated in late August for right facial (D) Norovirus nerve palsy of 2 days' duration. His initial evaluation in the emergency department included Lyme serology. Treatment was deferred pending test results. He is a landscaper in Rhode Island. Other medical history is unremarkable, and Item 18 A 62-year old man is evaluated for a fever. An indwelling tr he takes no medications. urinary catheter rvas inserted during coronary artery b1'pass On physical examination, vital signs are normal. He surgery 12 hours ago. Nurses obtained a urinalysis. has right-sided peripheral seventh cranial nerve palsy. The On physical examination. temperature is 38.1 oC remainder of his neurologic examination is normal. No rash (100.6 "F): the remainder of the vital signs and ph-v-sical is present. examination are noncontributory. The urinary catheter is Enzyme immunoassay is positive for Borreliaburgdor- removed. feri. B. burgdorferi IgM Western blot is also positive, and IgG Urinall,'sis sholt s 20 leukocytes, hpf. Western blot is negative. Whieh of the fbllowing is the most appropriate Which of the following is the most appropriate management? management? (A) Perform lumbar puncture (A) Obtain urine culture (B) Prescribe doxycycline (B) Repeat urinalysis (C) Prescribeprednisone (C) Start empiric antibiotics (D) Start parenteral ceftriaxone (D) Clinical observation 116

Self-Assessment Test P UI c, tr Item 19 A 34-year-old woman is evaluated in the emergency depart- to start treatment. HIV testing 1 year ago was negative. He takes no medications. The physical examination is normal. F *t F (u ment for a 3-day history of increasing urinary frequency, E urgency, and burning accompanied by right flank pain, The fourth generation HIV-112 antigen/antibody UI l,I fever, chills, nausea, and vomiting. She was treated with combination immunoassay is positive, with the differ- (u l,I trimethoprim-sulfamethoxazole for cystitis 2 weeks ago. entiation assay positive for HIV-1 antibody. HIV-1 quan- UI Medical history is also significant for nephrolithiasis. Her titative RNA is 25,640 copies/ml, and the CD4 cell count a

P UI c, tr Item 19 A 34-year-old woman is evaluated in the emergency depart- to start treatment. HIV testing 1 year ago was negative. He takes no medications. The physical examination is normal. F *t F (u ment for a 3-day history of increasing urinary frequency, E urgency, and burning accompanied by right flank pain, The fourth generation HIV-112 antigen/antibody UI l,I fever, chills, nausea, and vomiting. She was treated with combination immunoassay is positive, with the differ- (u l,I trimethoprim-sulfamethoxazole for cystitis 2 weeks ago. entiation assay positive for HIV-1 antibody. HIV-1 quan- UI Medical history is also significant for nephrolithiasis. Her titative RNA is 25,640 copies/ml, and the CD4 cell count a only other medication is an oral contraceptive pill. She is 540/pL. = (u rrt reports experiencing a rash with amoxicillin in childhood, but no adverse reactions to cephalosporin medications. Which of the following is the most appropriate On physical examination, temperature is 38.9 "C (102 "F), management? blood pressure is 92/60 mm Hg, and pulse rate is 96/min. (A) Antiretroviral therapy initiation now Palpation elicits right-sided costovertebral angle punch ten- (B) Antiretroviral therapy initiation when CD4 cell count derness. drops to less than 350/pL Urinalysis reveals cloudy urine with greater than 100 leukocytes/hpf, 0-5 erythrocyteslhpl and 4+ bacteria. (C) Conflrmatory HIV Western blot testing A urine pregnancy test is negative. (D) Repeat HIV-ll2 antigen/antibody combination immu- Bilateral, nonobstructing, small ureteral-pelvic junc- noassay and HIV quantitative RNA tion calculi are seen on kidney ultrasound.

only other medication is an oral contraceptive pill. She is 540/pL. = (u rrt reports experiencing a rash with amoxicillin in childhood, but no adverse reactions to cephalosporin medications. Which of the following is the most appropriate On physical examination, temperature is 38.9 "C (102 "F), management? blood pressure is 92/60 mm Hg, and pulse rate is 96/min. (A) Antiretroviral therapy initiation now Palpation elicits right-sided costovertebral angle punch ten- (B) Antiretroviral therapy initiation when CD4 cell count derness. drops to less than 350/pL Urinalysis reveals cloudy urine with greater than 100 leukocytes/hpf, 0-5 erythrocyteslhpl and 4+ bacteria. (C) Conflrmatory HIV Western blot testing A urine pregnancy test is negative. (D) Repeat HIV-ll2 antigen/antibody combination immu- Bilateral, nonobstructing, small ureteral-pelvic junc- noassay and HIV quantitative RNA tion calculi are seen on kidney ultrasound. Which of the following is the most appropriate intravenous treatment? (A) Aztreonam Item 22 An 8l-year-old man is evaluated in the emergency depart- tr ment fbr confusion, fever, and shaking chills overnight. (B) Ceftriaxone He has had increasing difficulty in fully emptying his (C) Ciprofloxacin bladder, urinary frequency, and dysuria for the past (D) Levofloxacin 3 days. He received a 7-day course of ciprofloxacin l month ago for cystitis with documented pyuria and bacteriuria. (E) Trimethoprim-sulfamethoxazole Medical history is also significant for benign prostatic hyperplasia. On physical examination, he is disoriented to the date. tr Item 2O A 30-year-old man is hospitalized fur sudden onset of severe Temperature is 38.9 "C (102 "F), blood pressure is 96160 mm Hg, pulse rate is 102lmin, and respiration rate is 20/min. The left biceps swelling and pain beginning 36 hours ago, which bladder is distended, but no costovertebral angle tenderness has rapidly progressed in the past 6 hours. He also reports is elicited. fbver and ehills. Medical history is significant fbr daily sub- A dipstick urinalysis shows 2+ blood; 3+ nitrites; and cutaneous ("skin popping") heroin use into the left biceps. 3+ leukocyte esterase. He takes no medications. On physical examination, temperature is 38.7 "C Whieh of the following is the moat appropriate (tot.z "F), blood pressure is 11oi 60 mm Hg, pulse rate is intravenous treatment? lloi min, and respiration rate is 24lmin. The left biceps area is exquisitely tender, with associated edema, warmth, and (A) Ampicillin overlying ecchymotic bullous lesions; crepitus and indura- (B) Cefepime and doxycycline tion are appreciated with palpation. (C) Ceftriaxone CT imaging reveals gas in deep tissues. (D) Levofloxacin Piperacillin-tazobactam and vancomycin are initiated, and the patient is taken for suryieal debridement where necrotizing fusciitis and myonecrosis are conflrmed; subse- quent cultures identify Clostrid i u m perfri nge ns. Item 23 A 24-year-old woman is evaluated for a 6-week history of Which of,the following is the mmt appropriate antihiotic weight loss, fever, night sweats, and productive cough, with treatment? recently increasing malaise and fatigue. She works in a state (A) Ceftazidime plus doxycycline prison. She takes no medications. (B) Ciprofloxacin plus doxycycline On physical examination, temperature is 38.6 'C (tOf.S 'F); other vital signs are normal. Pulmonary exam- (C) Penicillin plus clindamycin ination reveals bronchial breath sounds bilaterally over the (D) Current antibiotics posterior upper lung lobes. Chest radiograph shows a small cavity with infll- trates in the right and left upper lobes and hilar lymph- Item 21 adenopathy. A 3S-year-old man undergoes follow-up evaluation for a Sputum acid-fast bacilli stain is shown on the next positive HIV screening test obtained 3 days ago. He is ready page. Sputum culture is pending.

Which of the following is the most appropriate intravenous treatment? (A) Aztreonam Item 22 An 8l-year-old man is evaluated in the emergency depart- tr ment fbr confusion, fever, and shaking chills overnight. (B) Ceftriaxone He has had increasing difficulty in fully emptying his (C) Ciprofloxacin bladder, urinary frequency, and dysuria for the past (D) Levofloxacin 3 days. He received a 7-day course of ciprofloxacin l month ago for cystitis with documented pyuria and bacteriuria. (E) Trimethoprim-sulfamethoxazole Medical history is also significant for benign prostatic hyperplasia. On physical examination, he is disoriented to the date. tr Item 2O A 30-year-old man is hospitalized fur sudden onset of severe Temperature is 38.9 "C (102 "F), blood pressure is 96160 mm Hg, pulse rate is 102lmin, and respiration rate is 20/min. The left biceps swelling and pain beginning 36 hours ago, which bladder is distended, but no costovertebral angle tenderness has rapidly progressed in the past 6 hours. He also reports is elicited. fbver and ehills. Medical history is significant fbr daily sub- A dipstick urinalysis shows 2+ blood; 3+ nitrites; and cutaneous ("skin popping") heroin use into the left biceps. 3+ leukocyte esterase. He takes no medications. On physical examination, temperature is 38.7 "C Whieh of the following is the moat appropriate (tot.z "F), blood pressure is 11oi 60 mm Hg, pulse rate is intravenous treatment? lloi min, and respiration rate is 24lmin. The left biceps area is exquisitely tender, with associated edema, warmth, and (A) Ampicillin overlying ecchymotic bullous lesions; crepitus and indura- (B) Cefepime and doxycycline tion are appreciated with palpation. (C) Ceftriaxone CT imaging reveals gas in deep tissues. (D) Levofloxacin Piperacillin-tazobactam and vancomycin are initiated, and the patient is taken for suryieal debridement where necrotizing fusciitis and myonecrosis are conflrmed; subse- quent cultures identify Clostrid i u m perfri nge ns. Item 23 A 24-year-old woman is evaluated for a 6-week history of Which of,the following is the mmt appropriate antihiotic weight loss, fever, night sweats, and productive cough, with treatment? recently increasing malaise and fatigue. She works in a state (A) Ceftazidime plus doxycycline prison. She takes no medications. (B) Ciprofloxacin plus doxycycline On physical examination, temperature is 38.6 'C (tOf.S 'F); other vital signs are normal. Pulmonary exam- (C) Penicillin plus clindamycin ination reveals bronchial breath sounds bilaterally over the (D) Current antibiotics posterior upper lung lobes. Chest radiograph shows a small cavity with infll- trates in the right and left upper lobes and hilar lymph- Item 21 adenopathy. A 3S-year-old man undergoes follow-up evaluation for a Sputum acid-fast bacilli stain is shown on the next positive HIV screening test obtained 3 days ago. He is ready page. Sputum culture is pending. 117

Self-Assessment Test vt (D -ha On physical examination, vital signs are norrnal, and the examination is unremarkable. ut ut .D A chest radiograph is normal. u! ur J Which ofthe following is the most appropriate (D J management? 4 { (D (A) Ciprofloxacin and raxibacumab tt rlt (B) Doxycycline and anthrax vaccination (C) Doxycycline, meropenem, and linezolid (D) Isolation (E) Clinical observation

vt (D -ha On physical examination, vital signs are norrnal, and the examination is unremarkable. ut ut .D A chest radiograph is normal. u! ur J Which ofthe following is the most appropriate (D J management? 4 { (D (A) Ciprofloxacin and raxibacumab tt rlt (B) Doxycycline and anthrax vaccination (C) Doxycycline, meropenem, and linezolid (D) Isolation (E) Clinical observation Item 26 A 68-year-old man is evaluated for a 2-week history of fever and malaise. Medical history is significant for kidney transplantation 9 months ago. Donor serology was posi- tive for cytomegalovirus, and the patient was seronegative; he received valganciclovir prophylaxis for 6 months after transplantation. Medications are tacrolimus, mycophenolate mofetil, prednisone, and trimethoprim-sulfamethoxazole. On physical examination, temperature is 38.1 'C (1OO.O oF); other vital signs are norrnal. The physical exam- ination is normal. Which of the following is the most appropriate initial laboratory studies: treatment? Today l Month Ago (A) Clarithromycin and ethambutol Leukocyte count 22OOl1tL 6400l1tL (z.zx1oelL) (0.+ x loe/L) (B) Isoniazid Platelet count 100,000/pL 180,000/pL (C) Isoniazid, rifampin, pyrazinamide, and ethambutol (roo x loe/L) (rso x 1oe/L) (D) Rifampin, ethambutol, pyrazinamide, and levofloxacin Creatinine 1.2 mg/dl 1.1mg/dl (too pmol/L) (oz.z pmollL) Alanine 92U IL Normal Item 24 aminotransferase A 26-year-old woman undergoes consultation to update Aspartate 80 U/L Normal hervaccinations. She is an elementaryschoolteacher. Med- aminotransferase ical history is signiflcant for well-controlled HIV diagnosed A chest radiograph is normal. 6 years ago. Medications are tenofovir alafenamide, emtri- citabine, and dolutegravir. Which of the following infections is most likely present in The physical examination is normal. this patient? Her CD4 cell count is 520/pL and has been stable for several years. HIV viral load is undetectable. (A) Cytomegalovirus (B) Pneumocystis jirouecii Which of the following vaccines is contraindicated in this (C) Polyomavirus BK patient? (D) Polyomavirus JC (A) Humanpapillomavirus (B) Inactivatedinfluenza Item 27 (C) Measles-mumps-rubella A 3S-year-old man is evaluated for recurrent sinus infec- (D) Varicella tions. He indicates experiencing sinus infections lasting (E) No contraindications exist more than 2 weeks requiring antibiotics one to two times per year for the past 10 years. He reports frequent episodes of bronchitis and has been hospitalized twice for pneumo- Item 25 nia. Two years ago, he was diagnosed with giardiasis. He A 3S-year-old man is evaluated for potential anthrax expo- takes no medications. sure. He was informed that three coworkers with whom he On physical examination, vital signs are norrnal. The has had no close contact are being evaluated for suspected examination is unremarkable. cutaneous anthrax. Medical history is notable for a torn Laboratory studies show a quantitative IgG level of less Achilles tendon that was repaired 9 months ago. He takes than 500 mg/dl (5 g/L) and a normal complete blood count no medications. with differential.

Item 26 A 68-year-old man is evaluated for a 2-week history of fever and malaise. Medical history is significant for kidney transplantation 9 months ago. Donor serology was posi- tive for cytomegalovirus, and the patient was seronegative; he received valganciclovir prophylaxis for 6 months after transplantation. Medications are tacrolimus, mycophenolate mofetil, prednisone, and trimethoprim-sulfamethoxazole. On physical examination, temperature is 38.1 'C (1OO.O oF); other vital signs are norrnal. The physical exam- ination is normal. Which of the following is the most appropriate initial laboratory studies: treatment? Today l Month Ago (A) Clarithromycin and ethambutol Leukocyte count 22OOl1tL 6400l1tL (z.zx1oelL) (0.+ x loe/L) (B) Isoniazid Platelet count 100,000/pL 180,000/pL (C) Isoniazid, rifampin, pyrazinamide, and ethambutol (roo x loe/L) (rso x 1oe/L) (D) Rifampin, ethambutol, pyrazinamide, and levofloxacin Creatinine 1.2 mg/dl 1.1mg/dl (too pmol/L) (oz.z pmollL) Alanine 92U IL Normal Item 24 aminotransferase A 26-year-old woman undergoes consultation to update Aspartate 80 U/L Normal hervaccinations. She is an elementaryschoolteacher. Med- aminotransferase ical history is signiflcant for well-controlled HIV diagnosed A chest radiograph is normal. 6 years ago. Medications are tenofovir alafenamide, emtri- citabine, and dolutegravir. Which of the following infections is most likely present in The physical examination is normal. this patient? Her CD4 cell count is 520/pL and has been stable for several years. HIV viral load is undetectable. (A) Cytomegalovirus (B) Pneumocystis jirouecii Which of the following vaccines is contraindicated in this (C) Polyomavirus BK patient? (D) Polyomavirus JC (A) Humanpapillomavirus (B) Inactivatedinfluenza Item 27 (C) Measles-mumps-rubella A 3S-year-old man is evaluated for recurrent sinus infec- (D) Varicella tions. He indicates experiencing sinus infections lasting (E) No contraindications exist more than 2 weeks requiring antibiotics one to two times per year for the past 10 years. He reports frequent episodes of bronchitis and has been hospitalized twice for pneumo- Item 25 nia. Two years ago, he was diagnosed with giardiasis. He A 3S-year-old man is evaluated for potential anthrax expo- takes no medications. sure. He was informed that three coworkers with whom he On physical examination, vital signs are norrnal. The has had no close contact are being evaluated for suspected examination is unremarkable. cutaneous anthrax. Medical history is notable for a torn Laboratory studies show a quantitative IgG level of less Achilles tendon that was repaired 9 months ago. He takes than 500 mg/dl (5 g/L) and a normal complete blood count no medications. with differential. 118

Self-Assessment Test y UI (l, Which of the following is the most appropriate injection drug use. She has one sexual partner who is HIV l- management? F negative; she uses condoms regularly. -o (A) CD4 T-cell subset measurement Vital signs and physical examination are normal. E Laboratory studies: ta (B) Booster measles vaccination UI Fourth-generationHlV-Il2antigen/ Negative o Ut (C) IgG subset (IgG 1- levels) measurement t/l antibody combination assay (D) Serologic response to pneumococcal and tetanus Hepatitis B surface antibody Positive rt t vaccination Hepatitis B surface antigen Negative -r/t (u (E) Trimethoprim-sulfamethoxazole prophylaxis Hepatitis C antibody Negative A urine pregnancy test is negative. The patient is counseled regarding consistent condom tr Item 28 A 62-year-old man is evaluated in the emergency depart- use and use of clean needles and equipment. She is referred to substance abuse treatment. ment for progressively worsening lower back pain of 3 weeks' duration. He reports no extremity numbness, Which of the following is the most appropriate additional weakness, or radicular pain. Medical history is notable for management? hypertension, type 2 diabetes mellitus, and hemodialysis for end-stage kidney disease. Medications are amlodipine, (A) Tenofovir alafenamide, emtricitabine, and darunavir metoprolol, basal and prandial insulin, sevelamer, and a (B) Tenofovir alafenamide or tenofovir disoproxil fumarate multivitamin. (C) Tenofovir disoproxil fumarate and emtricitabine On physical examination, temperature is 37.8 "C (D) No additional management (tOO.t 'F), blood pressure is 150/90 mm Hg, pulse rate is 72lmin, and respiration rate is 16lmin. Neurologic exam- ination is normal. A functioning right arm flstula is present. Point tenderness is noted over the lower lumbar spine. Laboratory studies show a leukocyte count of 14,2OOl1tL Item 30 A72-year-old man is hospitalized for dyspnea, night sweats, tr (t+.ZxIOe lL). Two sets of blood cultures obtained yesterday and productive cough; symptoms began B months ago. are positive for gram-positive cocci in clusters; preliminary He also reports a 9.1-kg (20 lb) weight loss over the past identiflcation is coagulase-positive staphylococci. 12 months. Medical history is notable for COPD. He has a MRI of the thoracic and lumbar spine is shown. 60-pack-year smoking history. Medications are umeclidin- ium and vilanterol inhaler once daily. On physical examination, vital signs are normal. Pul- monary examination reveals diminished breath sounds. The remainder of the examination is normal. Sputum Gram stain shows abundant polymorphonu- clear cells but no organisms. Sputum acid-fast bacilli stains are positive. An interferon y release assay is negative. A chest radiograph is shown.

Self-Assessment Test y UI (l, Which of the following is the most appropriate injection drug use. She has one sexual partner who is HIV l- management? F negative; she uses condoms regularly. -o (A) CD4 T-cell subset measurement Vital signs and physical examination are normal. E Laboratory studies: ta (B) Booster measles vaccination UI Fourth-generationHlV-Il2antigen/ Negative o Ut (C) IgG subset (IgG 1- levels) measurement t/l antibody combination assay (D) Serologic response to pneumococcal and tetanus Hepatitis B surface antibody Positive rt t vaccination Hepatitis B surface antigen Negative -r/t (u (E) Trimethoprim-sulfamethoxazole prophylaxis Hepatitis C antibody Negative A urine pregnancy test is negative. The patient is counseled regarding consistent condom tr Item 28 A 62-year-old man is evaluated in the emergency depart- use and use of clean needles and equipment. She is referred to substance abuse treatment. ment for progressively worsening lower back pain of 3 weeks' duration. He reports no extremity numbness, Which of the following is the most appropriate additional weakness, or radicular pain. Medical history is notable for management? hypertension, type 2 diabetes mellitus, and hemodialysis for end-stage kidney disease. Medications are amlodipine, (A) Tenofovir alafenamide, emtricitabine, and darunavir metoprolol, basal and prandial insulin, sevelamer, and a (B) Tenofovir alafenamide or tenofovir disoproxil fumarate multivitamin. (C) Tenofovir disoproxil fumarate and emtricitabine On physical examination, temperature is 37.8 "C (D) No additional management (tOO.t 'F), blood pressure is 150/90 mm Hg, pulse rate is 72lmin, and respiration rate is 16lmin. Neurologic exam- ination is normal. A functioning right arm flstula is present. Point tenderness is noted over the lower lumbar spine. Laboratory studies show a leukocyte count of 14,2OOl1tL Item 30 A72-year-old man is hospitalized for dyspnea, night sweats, tr (t+.ZxIOe lL). Two sets of blood cultures obtained yesterday and productive cough; symptoms began B months ago. are positive for gram-positive cocci in clusters; preliminary He also reports a 9.1-kg (20 lb) weight loss over the past identiflcation is coagulase-positive staphylococci. 12 months. Medical history is notable for COPD. He has a MRI of the thoracic and lumbar spine is shown. 60-pack-year smoking history. Medications are umeclidin- ium and vilanterol inhaler once daily. On physical examination, vital signs are normal. Pul- monary examination reveals diminished breath sounds. The remainder of the examination is normal. Sputum Gram stain shows abundant polymorphonu- clear cells but no organisms. Sputum acid-fast bacilli stains are positive. An interferon y release assay is negative. A chest radiograph is shown. Which of the following is the most appropriate initial management? (A) Bone biopsy (B) Cefazolin (C) Vancomycin (D) Vancomycin and cefepime

Self-Assessment Test y UI (l, Which of the following is the most appropriate injection drug use. She has one sexual partner who is HIV l- management? F negative; she uses condoms regularly. -o (A) CD4 T-cell subset measurement Vital signs and physical examination are normal. E Laboratory studies: ta (B) Booster measles vaccination UI Fourth-generationHlV-Il2antigen/ Negative o Ut (C) IgG subset (IgG 1- levels) measurement t/l antibody combination assay (D) Serologic response to pneumococcal and tetanus Hepatitis B surface antibody Positive rt t vaccination Hepatitis B surface antigen Negative -r/t (u (E) Trimethoprim-sulfamethoxazole prophylaxis Hepatitis C antibody Negative A urine pregnancy test is negative. The patient is counseled regarding consistent condom tr Item 28 A 62-year-old man is evaluated in the emergency depart- use and use of clean needles and equipment. She is referred to substance abuse treatment. ment for progressively worsening lower back pain of 3 weeks' duration. He reports no extremity numbness, Which of the following is the most appropriate additional weakness, or radicular pain. Medical history is notable for management? hypertension, type 2 diabetes mellitus, and hemodialysis for end-stage kidney disease. Medications are amlodipine, (A) Tenofovir alafenamide, emtricitabine, and darunavir metoprolol, basal and prandial insulin, sevelamer, and a (B) Tenofovir alafenamide or tenofovir disoproxil fumarate multivitamin. (C) Tenofovir disoproxil fumarate and emtricitabine On physical examination, temperature is 37.8 "C (D) No additional management (tOO.t 'F), blood pressure is 150/90 mm Hg, pulse rate is 72lmin, and respiration rate is 16lmin. Neurologic exam- ination is normal. A functioning right arm flstula is present. Point tenderness is noted over the lower lumbar spine. Laboratory studies show a leukocyte count of 14,2OOl1tL Item 30 A72-year-old man is hospitalized for dyspnea, night sweats, tr (t+.ZxIOe lL). Two sets of blood cultures obtained yesterday and productive cough; symptoms began B months ago. are positive for gram-positive cocci in clusters; preliminary He also reports a 9.1-kg (20 lb) weight loss over the past identiflcation is coagulase-positive staphylococci. 12 months. Medical history is notable for COPD. He has a MRI of the thoracic and lumbar spine is shown. 60-pack-year smoking history. Medications are umeclidin- ium and vilanterol inhaler once daily. On physical examination, vital signs are normal. Pul- monary examination reveals diminished breath sounds. The remainder of the examination is normal. Sputum Gram stain shows abundant polymorphonu- clear cells but no organisms. Sputum acid-fast bacilli stains are positive. An interferon y release assay is negative. A chest radiograph is shown. Which of the following is the most appropriate initial management? (A) Bone biopsy (B) Cefazolin (C) Vancomycin (D) Vancomycin and cefepime Item 29 A 24-year-old woman is evaluated for HIV pre-exposure prophylaxis. She shares needles and other equipment for

Self-Assessment Test y UI (l, Which of the following is the most appropriate injection drug use. She has one sexual partner who is HIV l- management? F negative; she uses condoms regularly. -o (A) CD4 T-cell subset measurement Vital signs and physical examination are normal. E Laboratory studies: ta (B) Booster measles vaccination UI Fourth-generationHlV-Il2antigen/ Negative o Ut (C) IgG subset (IgG 1- levels) measurement t/l antibody combination assay (D) Serologic response to pneumococcal and tetanus Hepatitis B surface antibody Positive rt t vaccination Hepatitis B surface antigen Negative -r/t (u (E) Trimethoprim-sulfamethoxazole prophylaxis Hepatitis C antibody Negative A urine pregnancy test is negative. The patient is counseled regarding consistent condom tr Item 28 A 62-year-old man is evaluated in the emergency depart- use and use of clean needles and equipment. She is referred to substance abuse treatment. ment for progressively worsening lower back pain of 3 weeks' duration. He reports no extremity numbness, Which of the following is the most appropriate additional weakness, or radicular pain. Medical history is notable for management? hypertension, type 2 diabetes mellitus, and hemodialysis for end-stage kidney disease. Medications are amlodipine, (A) Tenofovir alafenamide, emtricitabine, and darunavir metoprolol, basal and prandial insulin, sevelamer, and a (B) Tenofovir alafenamide or tenofovir disoproxil fumarate multivitamin. (C) Tenofovir disoproxil fumarate and emtricitabine On physical examination, temperature is 37.8 "C (D) No additional management (tOO.t 'F), blood pressure is 150/90 mm Hg, pulse rate is 72lmin, and respiration rate is 16lmin. Neurologic exam- ination is normal. A functioning right arm flstula is present. Point tenderness is noted over the lower lumbar spine. Laboratory studies show a leukocyte count of 14,2OOl1tL Item 30 A72-year-old man is hospitalized for dyspnea, night sweats, tr (t+.ZxIOe lL). Two sets of blood cultures obtained yesterday and productive cough; symptoms began B months ago. are positive for gram-positive cocci in clusters; preliminary He also reports a 9.1-kg (20 lb) weight loss over the past identiflcation is coagulase-positive staphylococci. 12 months. Medical history is notable for COPD. He has a MRI of the thoracic and lumbar spine is shown. 60-pack-year smoking history. Medications are umeclidin- ium and vilanterol inhaler once daily. On physical examination, vital signs are normal. Pul- monary examination reveals diminished breath sounds. The remainder of the examination is normal. Sputum Gram stain shows abundant polymorphonu- clear cells but no organisms. Sputum acid-fast bacilli stains are positive. An interferon y release assay is negative. A chest radiograph is shown. Which of the following is the most appropriate initial management? (A) Bone biopsy (B) Cefazolin (C) Vancomycin (D) Vancomycin and cefepime Item 29 A 24-year-old woman is evaluated for HIV pre-exposure prophylaxis. She shares needles and other equipment for 119

Self-Assessment Test lrt .D On pl-rysical examination, temperature is 39'2 "C -D r+r ! UI UI tr CONI Which of the following is the most likely causative organism? (tOz.o "F). blood pressure is 125i60 mm Hg, pulse rate is 128i rnin. and respiration rate is 26lmin. Bilateral crackles .D UI (A) Mycobacterium ouiunt complex are heard ir-r the lungs. Abdomirral examination reveals UT (B) Mycobactenumntarinum hepatosplenornegaly. Minimal synovitis is present in the - d

UI UI tr CONI Which of the following is the most likely causative organism? (tOz.o "F). blood pressure is 125i60 mm Hg, pulse rate is 128i rnin. and respiration rate is 26lmin. Bilateral crackles .D UI (A) Mycobacterium ouiunt complex are heard ir-r the lungs. Abdomirral examination reveals UT (B) Mycobactenumntarinum hepatosplenornegaly. Minimal synovitis is present in the - d .D (C) Mycobacteriutn fuberculosis wrists and metacarpophalangeal joints bilaterally. i t;rboratory studies show a hemoglobin level of 7.5 gi dL {.D (D) Sfreptococcus pneuntoniae (75 gi L). leukocyte count of 4500/pL (4.5 x 10ei L), and plate (a t let count of 50,000/prl (50 x 10e/L). Item 31 Chest ratliograph shows bilateral reticulonodular infiltrates. A46-year-oldwoman is evaluated in the emergency depart- Blood cultures are negative. Peripheral blood smear is ment for a 2-day history of fever. She is also experiencing shown. tenderness at the laparoscopy site for a cholecystectomy performed 9 days ago. Medical history is otherwise noncon- tributory, and she takes no medications. ,# On physical examination, temperature is 38.3 oC (tot 'F); the remainder of the vital signs are normal. She has moderate tenderness and fullness in the right upper , quadrant with deep palpation. Minimal clear drainage is seen from one of the incision sites, but no erythema or ten- derness is noted. Laboratory studies show a leukocyte count of 14,300/pL (r+.9 x loe/L).

.D (C) Mycobacteriutn fuberculosis wrists and metacarpophalangeal joints bilaterally. i t;rboratory studies show a hemoglobin level of 7.5 gi dL {.D (D) Sfreptococcus pneuntoniae (75 gi L). leukocyte count of 4500/pL (4.5 x 10ei L), and plate (a t let count of 50,000/prl (50 x 10e/L). Item 31 Chest ratliograph shows bilateral reticulonodular infiltrates. A46-year-oldwoman is evaluated in the emergency depart- Blood cultures are negative. Peripheral blood smear is ment for a 2-day history of fever. She is also experiencing shown. tenderness at the laparoscopy site for a cholecystectomy performed 9 days ago. Medical history is otherwise noncon- tributory, and she takes no medications. ,# On physical examination, temperature is 38.3 oC (tot 'F); the remainder of the vital signs are normal. She has moderate tenderness and fullness in the right upper , quadrant with deep palpation. Minimal clear drainage is seen from one of the incision sites, but no erythema or ten- derness is noted. Laboratory studies show a leukocyte count of 14,300/pL (r+.9 x loe/L). Which of the following is the most appropriate management? (A) Abdominal CT (B) Cephalexin "k'B "dh (C) Gram stain and culture of incision site drainage (D) Piperacillin-tazobactam The l{istoplasmaurinary antigen assay is positive.

Which of the following is the most appropriate management? (A) Abdominal CT (B) Cephalexin "k'B "dh (C) Gram stain and culture of incision site drainage (D) Piperacillin-tazobactam The l{istoplasmaurinary antigen assay is positive. tr Item 32 A 28 year-old man is evaluated 24 hours after hospital- Which of the following is the most appropriate treatment? (A) Fluconazole ization for hemorrhagic shock following a motor vehicle accident. In the emergency department a femoral cer-rtral (B) Itraconazole venous catheter was inserted emergently. (C) Liposomalamphotericin B On physical examination, temperature is 37.6 'C (D) Posaconazole (99.6 'F), and other vital signs are normal. The left femoral central venous access site is intact with a small amount of blood on the dressing.

tr Item 32 A 28 year-old man is evaluated 24 hours after hospital- Which of the following is the most appropriate treatment? (A) Fluconazole ization for hemorrhagic shock following a motor vehicle accident. In the emergency department a femoral cer-rtral (B) Itraconazole venous catheter was inserted emergently. (C) Liposomalamphotericin B On physical examination, temperature is 37.6 'C (D) Posaconazole (99.6 'F), and other vital signs are normal. The left femoral central venous access site is intact with a small amount of blood on the dressing. Which of the following is the most appropriate Item 34 A 78-year-old man was hospitalized 2 days ago for man tr agement of lower back pain that has been worsening management of the central venous catheter? over the past 4 weeks and remained uncontrolled with (A) Obtain two sets of blood cultures from the femoral oral pain medications. He reports no radicular symptoms, catheter weakness. or bladder or bowel incontinence. Medical his- (B) Monitor for signs of infection tory is ncltable for benign prostatic hyperplasia treated (C) Replace the femoral catheter over a guidewire with tamsulosin. On physical examination, the patient appears in dis- (D) Replace the femoral catheter with a subclavian catheter tress from pain. Temperature is 37.9 "C (100.2 "F'), blood pressure is 155/85 mm Hg, pulse rate is 82/min. and res piration rate is 18/min. Tenderness to palpation is elicited Item 33 over the lower lumbar spine. Lower extremity strength is A 24-year-old woman is hospitalized for increasing short- normal, with intact sensation and normal reflexes. ness of breath, fatigue, productive cough, and pleuritic Laboratory studies shon,a hemoglobin level of 12.2 gldL chest pain of 2 weeks' duration; she has also been experi- (tzzgtL) and leukocyte count of 15,600/pL (15.6 x 10e/L). encing fever and chills for the past month. She has rheuma- MRI with contrast reveals evidence of L:l L4 discitis with toid arthritis diagnosed 4 years ago. She lives in northern osteomyelitis involving the contiguous vertebral body end Georgia. Her medications are methotrexate, etanercept. plates at L3 and L4, without evidence of epidural abscess. low-dose prednisone, and ibuprofen as needed. Blood and urine cultures are negative at 48 hours.

Which of the following is the most appropriate Item 34 A 78-year-old man was hospitalized 2 days ago for man tr agement of lower back pain that has been worsening management of the central venous catheter? over the past 4 weeks and remained uncontrolled with (A) Obtain two sets of blood cultures from the femoral oral pain medications. He reports no radicular symptoms, catheter weakness. or bladder or bowel incontinence. Medical his- (B) Monitor for signs of infection tory is ncltable for benign prostatic hyperplasia treated (C) Replace the femoral catheter over a guidewire with tamsulosin. On physical examination, the patient appears in dis- (D) Replace the femoral catheter with a subclavian catheter tress from pain. Temperature is 37.9 "C (100.2 "F'), blood pressure is 155/85 mm Hg, pulse rate is 82/min. and res piration rate is 18/min. Tenderness to palpation is elicited Item 33 over the lower lumbar spine. Lower extremity strength is A 24-year-old woman is hospitalized for increasing short- normal, with intact sensation and normal reflexes. ness of breath, fatigue, productive cough, and pleuritic Laboratory studies shon,a hemoglobin level of 12.2 gldL chest pain of 2 weeks' duration; she has also been experi- (tzzgtL) and leukocyte count of 15,600/pL (15.6 x 10e/L). encing fever and chills for the past month. She has rheuma- MRI with contrast reveals evidence of L:l L4 discitis with toid arthritis diagnosed 4 years ago. She lives in northern osteomyelitis involving the contiguous vertebral body end Georgia. Her medications are methotrexate, etanercept. plates at L3 and L4, without evidence of epidural abscess. low-dose prednisone, and ibuprofen as needed. Blood and urine cultures are negative at 48 hours. 120

Self-Assessment Test t,UI q, tr CONT. Which of the following is the most appropriate management? Which of the following is the most appropriate management? F y E (l, (A) Disk space aspiration/biopsy (A) Azithromycin E UI (B) Open bone biopsy (B) Baloxavir l,I q, (C) Vancomycin (C) Influenza polymerase chain reaction testing UI l,I (D) Vancomycin and ceftriaxone (D) Oseltamivir a

t,UI q, tr CONT. Which of the following is the most appropriate management? Which of the following is the most appropriate management? F y E (l, (A) Disk space aspiration/biopsy (A) Azithromycin E UI (B) Open bone biopsy (B) Baloxavir l,I q, (C) Vancomycin (C) Influenza polymerase chain reaction testing UI l,I (D) Vancomycin and ceftriaxone (D) Oseltamivir a (E) Supportive care =q, t/t Item 35 A 43-year-old man is hospitalized for shortness of breath, tingling in the extremities, andweakness. Three weeks ago, he had watery diarrhea that lasted 5 days. He reports no Item 38 A 28-year-old man is hospitalized for cough, headaches, tr nausea, and vomiting of 1 week's duration. Two days ago, travel and no sexual contact in the past year. He takes no he developed a stiff neck. He has otherwise been well and medications. takes no medications. On physical examination, temperature is 37.2 "C On physical examination, temperature is 38 oC (98.9 "F), blood pressure is 140/90 mm Hg, pulse rate is (tOO.+ "F), blood pressure is 110/60 mm Hg, pulse rate is 101/min, and respiration rate is 22lmin. Oxygen satura- lL2lmin, and respiration rate is 2Zlmin. Nuchal rigidity tion is 93o/o breathing ambient air. Neurologic examina- is present; neurologic examination is normal. Abdominal tion reveals no movement in the lower extremities and examination reveals hepatosplenomegaly. only 3/5 upper extremity strength bilaterally. Diminished Cerebrospinal fluid studies: or absent deep tendon reflexes are present throughout. Pressure, opening 240 mm HrO Sensory examination is intact. Lung sounds are diminished, Leukocyte count 100/pL (tOO x 106/L); 80% with poor inspiratory effort. lymphocytes Glucose 35 mg/dl (1.9 mmolil) Which of the following is the most Hkely cause of this Protein 155 mgldl (1SSO mg/L) patient's neurologic syndrome? HIV antigen/antibody combination immunoassay is (A) Botulism negative. Blood cultures are negative. Cryptococcal serum (B) Campylobocterinfection and cerebrospinal fluid antigen test is pending. Cerebrospi- (C) West Nile virus infection nal fluid Gram stain findings are shown. (D) Zika virus infection

(E) Supportive care =q, t/t Item 35 A 43-year-old man is hospitalized for shortness of breath, tingling in the extremities, andweakness. Three weeks ago, he had watery diarrhea that lasted 5 days. He reports no Item 38 A 28-year-old man is hospitalized for cough, headaches, tr nausea, and vomiting of 1 week's duration. Two days ago, travel and no sexual contact in the past year. He takes no he developed a stiff neck. He has otherwise been well and medications. takes no medications. On physical examination, temperature is 37.2 "C On physical examination, temperature is 38 oC (98.9 "F), blood pressure is 140/90 mm Hg, pulse rate is (tOO.+ "F), blood pressure is 110/60 mm Hg, pulse rate is 101/min, and respiration rate is 22lmin. Oxygen satura- lL2lmin, and respiration rate is 2Zlmin. Nuchal rigidity tion is 93o/o breathing ambient air. Neurologic examina- is present; neurologic examination is normal. Abdominal tion reveals no movement in the lower extremities and examination reveals hepatosplenomegaly. only 3/5 upper extremity strength bilaterally. Diminished Cerebrospinal fluid studies: or absent deep tendon reflexes are present throughout. Pressure, opening 240 mm HrO Sensory examination is intact. Lung sounds are diminished, Leukocyte count 100/pL (tOO x 106/L); 80% with poor inspiratory effort. lymphocytes Glucose 35 mg/dl (1.9 mmolil) Which of the following is the most Hkely cause of this Protein 155 mgldl (1SSO mg/L) patient's neurologic syndrome? HIV antigen/antibody combination immunoassay is (A) Botulism negative. Blood cultures are negative. Cryptococcal serum (B) Campylobocterinfection and cerebrospinal fluid antigen test is pending. Cerebrospi- (C) West Nile virus infection nal fluid Gram stain findings are shown. (D) Zika virus infection Item 36 A 32-year-old woman undergoes consultation for recur- rent symptomatic lower urinary tract infections. They have increased in frequency over the past 3 years to a rate ofabout two times per year. She has been unable to relate onset to any speciflc activity. Symptoms resolve quicklywith initiation of prescribed antibiotics. She is otherwise well.

Item 36 A 32-year-old woman undergoes consultation for recur- rent symptomatic lower urinary tract infections. They have increased in frequency over the past 3 years to a rate ofabout two times per year. She has been unable to relate onset to any speciflc activity. Symptoms resolve quicklywith initiation of prescribed antibiotics. She is otherwise well. Which of the following is the most appropriate management? (A) Daily cranberry tablets (B) DailyD-mannosesupplementation Which of the following is the most appropriate treatment? (C) Nightly prophylaxis with low-dose ciprofloxacin (D) Self-treatment with nitrofurantoin (A) Acyclovir (E) Urination immediately after sexual intercourse (B) Caspofungin (C) Liposomal amphotericin B and flucytosine (D) Vancomycin and ceftriaxone Item 37 A 47-year-old woman is evaluated during influenza season for a 3-day history of fever, myalgia, rhinorrhea, and non- productive cough. She lives alone and works as a medical Item 39 A 42-year-old man is evaluated in the emergency depart- tr editor. She is otherwise well and takes no medications. ment for a 2-day history of redness and pain at the site of a On physical examination, temperature is 38 oC recent insect bite. Medical history is otherwise noncontrib- (fOO.+ 'F), blood pressure is 145/85 mm Hg, pulse rate is utory, and he takes no medications. 88/min, and respiration rate is 18/min. The pulmonary and On physical examination, temperature is 38.8 'C remainder of the examination is normal. (rOr.q 'F), blood pressure is 110i70 mm Hg, pulse rate is 121

Self-Assessment Test lrt (D -t + 105i min, and respiration rate is l8/min. A poorly defined, dif- (C) Hepatitis B adjuvant vaccine D til UI E fuse, 4- x S-cm erythematous area is located on the distal left (D) Hepatitis B immune globulin UI c0NT' 1o*"r extremity; it is warm and edematous but without puru- .D UI lence, induration, or fluctuance. No other findings are present. UI Laboratory studies show a leukocyte count of 15,000/pL tr J J .D Item 42 (ts x roe/L). A 7S-year-old woman is hospitalized with a 2-day history J a.t { (D of lethargy, headache, and confusion in September. She is Ut Which of the following is the most appropriate antibiotic ?t an avid gardener living in Connecticut. Medical history is therapy? unremarkable, and she takes no medications. (A) Cefazolin On physical examination, temperature is 38.9 "C (B) Doxycycline (tOZ 'f') and pulse rate is 110/min. She is lethargic and ori-

lrt (D -t + 105i min, and respiration rate is l8/min. A poorly defined, dif- (C) Hepatitis B adjuvant vaccine D til UI E fuse, 4- x S-cm erythematous area is located on the distal left (D) Hepatitis B immune globulin UI c0NT' 1o*"r extremity; it is warm and edematous but without puru- .D UI lence, induration, or fluctuance. No other findings are present. UI Laboratory studies show a leukocyte count of 15,000/pL tr J J .D Item 42 (ts x roe/L). A 7S-year-old woman is hospitalized with a 2-day history J a.t { (D of lethargy, headache, and confusion in September. She is Ut Which of the following is the most appropriate antibiotic ?t an avid gardener living in Connecticut. Medical history is therapy? unremarkable, and she takes no medications. (A) Cefazolin On physical examination, temperature is 38.9 "C (B) Doxycycline (tOZ 'f') and pulse rate is 110/min. She is lethargic and ori- (C) Trimethoprim-sulfamethoxazole ented only to name. She resists passive flexion of the neck and the ocular examination. No rash is present, and the (D) Vancomycin remainder of the examination is normal. (E) Vancomycin and piperacillin tazobactam Laboratory studies show a normal complete blood count and liver chemistry tests. Cerebrospinal fluid Item 40 shows a leukocyte count of 94lytL (g+ x 106/L), with 88'/, lymphocytes, 11% monocytes, and 1'X, polymorphonuclear An 18-year-old man is evaluated for a 2-day history of pru- cells. ritic rash. He sits nightly in his hot tub. He has not had a Serology for Borrelia burgdorferi is negative. rash like this before. Medical history is unremarkable, and he takes no medications. Which of the following is the most likely diagnosis? On physical examination, vital signs are normal. Several tender erythematous papulopustules are located (A) Anaplasmosis primarily over his buttocks. (B) Babesiosis (C) Lyme disease Which of the following is the most appropriate management for this patient? (D) Powassan virus infection (A) Cephalexin (B) Ciprofloxacin Item 43 (C) Doxycycline A Sl-year-old woman is hospitalized for fever, confu- (D) Observation sion, tremors, involuntary movements of her arms and legs, and lower extremity weakness. Her illness began Item 41 with fever, malaise and headache quickly followed by neurologic symptoms. She was airlifted from China back A 42-year-old woman is evaluated for hepatitis B reacti- to the United States. She has spent the last 3 months vation risk before deceased donor kidney transplantation working in rural and urban areas of Nepal, South Korea, for end-stage kidney disease. Medical history is signifl- Vietnam, and China. Her only travel-related precau- cant for chronic hepatitis B and hypertension. Medications tions have been daily atovaquone-proguanil to prevent are labetalol, amlodipine, cholecalciferol, sevelamer, and malaria. Medical history is unremarkable, and she takes sodium bicarbonate. no other medications. On physical examination, vital signs are normal. A On physical examination, she is confused. Tempera- mature arteriovenous fistula is located over the right arm. ture is 38.8 "C (f Of .S'F); othervital signs are normal. Nuchal Abdominal examination reveals no hepatomegaly. rigidity is noted. Choreoathetoid movements are observed. Laboratory studies completed l week ago: The remainder of the physical examination is normal. Alanine aminotransferase 10 U/L A lumbar puncture is performed. HIV-ll2 antigen/antibody testing Negative Cerebrospinal fluid studies: Hepatitis B surface antigen Positive Leukocyte count 94l1tL (g+xtOoL) Hepatitis B surface antibody Negative Erythrocytes s/pl (5 x 106/L) Hepatitis B core total antibody Positive HepatitisBeantigen Glucose 65 mg/dl (3.6 mmol/L) Negative Protein 97 mgldL (erc mglL) HepatitisBeantibody Positive Hepatitis B DNA 92O U lmL MRI of the brain with contrast shows abnormalities in the basal ganglia and thalamus. Ultrasound performed 1 month ago is negative for cir- rhosis and hepatocellular carcinoma. Which of the following is the most likely diagnosis? Which of the following is the most appropriate (A) Japaneseencephalitis management for this patient after transplantation? (B) Scrub typhus (A) Alanine aminotransferase monitoring (C) Tick-borne encephalitis (B) Entecavir (D) Yellow fever

(C) Trimethoprim-sulfamethoxazole ented only to name. She resists passive flexion of the neck and the ocular examination. No rash is present, and the (D) Vancomycin remainder of the examination is normal. (E) Vancomycin and piperacillin tazobactam Laboratory studies show a normal complete blood count and liver chemistry tests. Cerebrospinal fluid Item 40 shows a leukocyte count of 94lytL (g+ x 106/L), with 88'/, lymphocytes, 11% monocytes, and 1'X, polymorphonuclear An 18-year-old man is evaluated for a 2-day history of pru- cells. ritic rash. He sits nightly in his hot tub. He has not had a Serology for Borrelia burgdorferi is negative. rash like this before. Medical history is unremarkable, and he takes no medications. Which of the following is the most likely diagnosis? On physical examination, vital signs are normal. Several tender erythematous papulopustules are located (A) Anaplasmosis primarily over his buttocks. (B) Babesiosis (C) Lyme disease Which of the following is the most appropriate management for this patient? (D) Powassan virus infection (A) Cephalexin (B) Ciprofloxacin Item 43 (C) Doxycycline A Sl-year-old woman is hospitalized for fever, confu- (D) Observation sion, tremors, involuntary movements of her arms and legs, and lower extremity weakness. Her illness began Item 41 with fever, malaise and headache quickly followed by neurologic symptoms. She was airlifted from China back A 42-year-old woman is evaluated for hepatitis B reacti- to the United States. She has spent the last 3 months vation risk before deceased donor kidney transplantation working in rural and urban areas of Nepal, South Korea, for end-stage kidney disease. Medical history is signifl- Vietnam, and China. Her only travel-related precau- cant for chronic hepatitis B and hypertension. Medications tions have been daily atovaquone-proguanil to prevent are labetalol, amlodipine, cholecalciferol, sevelamer, and malaria. Medical history is unremarkable, and she takes sodium bicarbonate. no other medications. On physical examination, vital signs are normal. A On physical examination, she is confused. Tempera- mature arteriovenous fistula is located over the right arm. ture is 38.8 "C (f Of .S'F); othervital signs are normal. Nuchal Abdominal examination reveals no hepatomegaly. rigidity is noted. Choreoathetoid movements are observed. Laboratory studies completed l week ago: The remainder of the physical examination is normal. Alanine aminotransferase 10 U/L A lumbar puncture is performed. HIV-ll2 antigen/antibody testing Negative Cerebrospinal fluid studies: Hepatitis B surface antigen Positive Leukocyte count 94l1tL (g+xtOoL) Hepatitis B surface antibody Negative Erythrocytes s/pl (5 x 106/L) Hepatitis B core total antibody Positive HepatitisBeantigen Glucose 65 mg/dl (3.6 mmol/L) Negative Protein 97 mgldL (erc mglL) HepatitisBeantibody Positive Hepatitis B DNA 92O U lmL MRI of the brain with contrast shows abnormalities in the basal ganglia and thalamus. Ultrasound performed 1 month ago is negative for cir- rhosis and hepatocellular carcinoma. Which of the following is the most likely diagnosis? Which of the following is the most appropriate (A) Japaneseencephalitis management for this patient after transplantation? (B) Scrub typhus (A) Alanine aminotransferase monitoring (C) Tick-borne encephalitis (B) Entecavir (D) Yellow fever 122

Self-Assessment Test P UI Item 44 COVID-19 testing is negative. 6' F P A 34-year-old woman is evaluated for painful genital ulcers L (, that began 2 days ago. Three years ago, she was diagnosed Which of the following is the most appropriate E with primary genital herpes simplex virus type 2 but has management? Ut Ut not had a recurrence since then. The patient has not been (, (A) Obtain influenza polymerase chain reaction test; start UI UI sexually active for the past year. She takes no medications. oseltamivir On physical examination, vital signs are normal. The rF a

P UI Item 44 COVID-19 testing is negative. 6' F P A 34-year-old woman is evaluated for painful genital ulcers L (, that began 2 days ago. Three years ago, she was diagnosed Which of the following is the most appropriate E with primary genital herpes simplex virus type 2 but has management? Ut Ut not had a recurrence since then. The patient has not been (, (A) Obtain influenza polymerase chain reaction test; start UI UI sexually active for the past year. She takes no medications. oseltamivir On physical examination, vital signs are normal. The rF a (B) Obtain influenza serology; start baloxavir E q, left inguinal lymph nodes are palpable and tender. Three vt ulcerated lesions are present on the inner aspect of the left (C) Obtain rapid influenza antigen test; start zanamivir labia majora. The remainder of the examination is normal. (D) Obtain viral culture; start peramivir

(B) Obtain influenza serology; start baloxavir E q, left inguinal lymph nodes are palpable and tender. Three vt ulcerated lesions are present on the inner aspect of the left (C) Obtain rapid influenza antigen test; start zanamivir labia majora. The remainder of the examination is normal. (D) Obtain viral culture; start peramivir Which of the following is the most appropriate management? Item 47 (A) Benzathinepenicillin A 38-year-old man is evaluated inthe emergencydepartment (B) Nucleic acid ampliflcation testing for a 3-day history of daily fevers up to 39.4 'C (103 "F), head- (C) Type-speciflc herpes simplex serologic testing aches, myalgia, arthralgia, back pain, and nausea. Symptoms (D) Valacyclovir began 5 days after returning from a vacation in Ecuador, during which he spent time hiking in the forest. On physical examination, temperature is 39.4 oC tr Item 45 A62-year-old woman is evaluated in the emergency depart- (tOZ.g'F); other vital signs are normal. He has petechial lesions onthe distal right arm afterablood pressure measurement was taken on that arm. The remainder of the examination is normal. ment with a self-diagnosis of shingles. Medical history is notable fbr chickenpox as a child and breast cancer; she is l.aboratory studies: receiving chemotherapy with doxorubicin. cyclophospha Hematocrit 4r7,, mide, and paclitaxel. Leukocyte count 2850/pL (Z.q xrce lL) The lesions are shown. Platelet count 82,000/pL (SZ x rOslt) Alanine aminotransferase t92U lL Aspartate aminotransferase L76UIL Creatinine 1.4 mgldL (tz+ pmollL)

Which of the following is the most appropriate management? Item 47 (A) Benzathinepenicillin A 38-year-old man is evaluated inthe emergencydepartment (B) Nucleic acid ampliflcation testing for a 3-day history of daily fevers up to 39.4 'C (103 "F), head- (C) Type-speciflc herpes simplex serologic testing aches, myalgia, arthralgia, back pain, and nausea. Symptoms (D) Valacyclovir began 5 days after returning from a vacation in Ecuador, during which he spent time hiking in the forest. On physical examination, temperature is 39.4 oC tr Item 45 A62-year-old woman is evaluated in the emergency depart- (tOZ.g'F); other vital signs are normal. He has petechial lesions onthe distal right arm afterablood pressure measurement was taken on that arm. The remainder of the examination is normal. ment with a self-diagnosis of shingles. Medical history is notable fbr chickenpox as a child and breast cancer; she is l.aboratory studies: receiving chemotherapy with doxorubicin. cyclophospha Hematocrit 4r7,, mide, and paclitaxel. Leukocyte count 2850/pL (Z.q xrce lL) The lesions are shown. Platelet count 82,000/pL (SZ x rOslt) Alanine aminotransferase t92U lL Aspartate aminotransferase L76UIL Creatinine 1.4 mgldL (tz+ pmollL) Which of the following is the most likely diagnosis? (A) Chikungunya virus infection (B) Dengue virus infection (C) Leptospirosis w"r#&.

Which of the following is the most likely diagnosis? (A) Chikungunya virus infection (B) Dengue virus infection (C) Leptospirosis w"r#&. (D) Typhoid (enteric) fever

Which of the following is the most likely diagnosis? (A) Chikungunya virus infection (B) Dengue virus infection (C) Leptospirosis w"r#&. (D) Typhoid (enteric) fever Item 48 A 74-year-old rnan is evaluatecl in the errergency depart- tr ment for a 24-hour history of headache, stifl neck, f'ever. and altered mental status. Which of the following transmission-based precautions On pl-rysical examinatiotr, temperature is 39.1 'C (102.,1 'F). should be initiated? bloocl pressure is 100/68 mnt Hg. pulse rate is 124lmin. and respiration rate is lT lntin. 'lhe patient has a score of 12 on the (A) Airborneprecautions Glasgow Coma Scale. Neurologic examination is ttonfocill. (B) Airborne and contact precautions Cerebrospinal fluid studies revertl a leukocyte count of' (C) Contact precautions 2354l1t"L (ZgS+ x 106i l-) with 90'X, neutrophils. glt"tcose level (D) Contact and droplet precautions of 17 rngrdl (0.9 mrnoli'L), and protein level of'295 tngicll, (zqso mgi L). (E) Dropletprecautions Gram stait-r of the cerebrospir-ral fluid is negative, irnd a culture is pending. Item 46 CT of'the head lt,ithout contrast shows t-to itrtracranial lesions but does reveal pansinusitis. A 4S-year-old man is evaluated in December with a 1-day history of runny nose, low-grade fever, headache, myalgia, and cough. He received the inactivated influenza vaccine Which of the following is the most appropriate empiric 3 months ago. Medical history is notable for rheumatoid therapy? arthritis. His medications are methotrexate, etanercept, and (A) Vancomycin. ar-ripicillin, ancl ceftriaxolre low-dose prednisone. (B) Vancomycin, ampicillin, cettriaxone, iind dexamethasone On physical examination, temperature is 39.1 oC (fOZ.g "F); the remainder of the vital signs and physical (C) Vancornycin and ceftriaxone examination are normal. (D) Vancomycin, cef'epirne. and :rcyclovir

Item 48 A 74-year-old rnan is evaluatecl in the errergency depart- tr ment for a 24-hour history of headache, stifl neck, f'ever. and altered mental status. Which of the following transmission-based precautions On pl-rysical examinatiotr, temperature is 39.1 'C (102.,1 'F). should be initiated? bloocl pressure is 100/68 mnt Hg. pulse rate is 124lmin. and respiration rate is lT lntin. 'lhe patient has a score of 12 on the (A) Airborneprecautions Glasgow Coma Scale. Neurologic examination is ttonfocill. (B) Airborne and contact precautions Cerebrospinal fluid studies revertl a leukocyte count of' (C) Contact precautions 2354l1t"L (ZgS+ x 106i l-) with 90'X, neutrophils. glt"tcose level (D) Contact and droplet precautions of 17 rngrdl (0.9 mrnoli'L), and protein level of'295 tngicll, (zqso mgi L). (E) Dropletprecautions Gram stait-r of the cerebrospir-ral fluid is negative, irnd a culture is pending. Item 46 CT of'the head lt,ithout contrast shows t-to itrtracranial lesions but does reveal pansinusitis. A 4S-year-old man is evaluated in December with a 1-day history of runny nose, low-grade fever, headache, myalgia, and cough. He received the inactivated influenza vaccine Which of the following is the most appropriate empiric 3 months ago. Medical history is notable for rheumatoid therapy? arthritis. His medications are methotrexate, etanercept, and (A) Vancomycin. ar-ripicillin, ancl ceftriaxolre low-dose prednisone. (B) Vancomycin, ampicillin, cettriaxone, iind dexamethasone On physical examination, temperature is 39.1 oC (fOZ.g "F); the remainder of the vital signs and physical (C) Vancornycin and ceftriaxone examination are normal. (D) Vancomycin, cef'epirne. and :rcyclovir 123

Self-Assessment Test lrt .D -? Item 49 (C) Isoniazid D UI A 62-year -old woman undergoes preoperative evaluation for (D) No further testing or treatment UI .D UI total hip arthroplasty. Medical history is notable for diabetes UI mellitus, osteoarthritis, and liver transplantation 7 years ago J J for hepatitis C-related cirrhosis. Medications are tacrolimus, Item 52 .D J mycophenolate, metformin, and acetaminophen. A 55 year-old man is hospitalized for fever, chills, weak { rlt (D On physical examination, vital signs are normal. She ness, and malaise beginning earlier in the day. His dog UI has limited active right hip range of motion, but physical scratched his right calf 4 days ago and has licked the site -t examination flndings are otherwise normal. multiple times since. Medical history is notable for alcoholic Microscopic urinalysis results show 5-10 erythrocytesi cirrhosis. He takes no medications. hpl 10-20 leukocytes/hpf, and 3+ bacteria. On physical examination, temperature is 38.8 'C (fot.s 'F), blood pressure is 88i60 mm Hg, pulse rate is Which of the following is the most appropriate 120/min, and respiration rate is 25/min. A small tender management of this patient's bacteriuria? cut is located on the right posterior calf with surrounding erythema and associated warmth. (A) Cancelation of surgery Peripheral blood smear is shown. (B) Extended surgical antibiotic prophylaxis postopera- tively (C) Presurgical trimethoprim-sulfamethoxazole (D) Urine culture and sensitivity (E) No further management

(D On physical examination, vital signs are normal. She ness, and malaise beginning earlier in the day. His dog UI has limited active right hip range of motion, but physical scratched his right calf 4 days ago and has licked the site -t examination flndings are otherwise normal. multiple times since. Medical history is notable for alcoholic Microscopic urinalysis results show 5-10 erythrocytesi cirrhosis. He takes no medications. hpl 10-20 leukocytes/hpf, and 3+ bacteria. On physical examination, temperature is 38.8 'C (fot.s 'F), blood pressure is 88i60 mm Hg, pulse rate is Which of the following is the most appropriate 120/min, and respiration rate is 25/min. A small tender management of this patient's bacteriuria? cut is located on the right posterior calf with surrounding erythema and associated warmth. (A) Cancelation of surgery Peripheral blood smear is shown. (B) Extended surgical antibiotic prophylaxis postopera- tively (C) Presurgical trimethoprim-sulfamethoxazole (D) Urine culture and sensitivity (E) No further management Item 5O An 84-year-old woman is evaluated 2 days after hospitaliza- tion for pneumonia. Initial treatment included ceftriaxone and azithromycin, but azithromycin was stopped following a negative urine Legionella antigen test. She is clinically improved and is able to eat and maintain oral hydration. On physical examination, temperature is 37.7 'C (99.9 'F), blood pressure is 126184 mm Hg, pulse rate is B2lmin, and respiration rate is 18imin. Oxygen saturation Which of the following is the most likely cause of this is 98% breathing ambient air. Pulmonary examination infection? reveals crackles in the right lower lung fleld. Laboratory studies show a leukocyte count of 97OOl1:.L (A) Capnocytophaga canimorsus (g.z x10e/L), improved from 15,400/pL (15.4 x 10e/L). (B) Erysipelothrixrhusiopathiae Admission chest radiograph showed a right lower lobe (C) Mycobacterium marinum inflltrate without a pulmonary effusion. (D) Vibrio uulnificus Which of the following is the most appropriate management? (A) Continueceftriaxone Item 53 A 46-year-old woman is hospitalized with pyelonephritis; tr (B) Measure procalcitonin level empiric ceftriaxone is initiated. Medical history is significant for two urinary tract infections in the previous 15 months (C) Repeat chest radiography treated with ciprofloxacin; her last infection 3 months ago (D) Switch to oral amoxicillin was caused by Escherichia coli resistant to ampicillin and cephalexin. She takes no other medications. On physical examination. temperature is 38.4 "C Item 51 (fOt.Z "F), blood pressure is 105/70 mm Hg, pulse rate is A 2O-year-old woman undergoes follow-up consultation. 106i min, and respiration rate is 2llmin. She has left flank She developed an 8-mm induration on tuberculin skin test- tenderness to palpation. ing during a pre-employment physical examination. She Urine culture reveals more than 10s cfu/ml of E. colt will work as a receptionist in a university internal medicine sensitive to cefepime. ertapenem, and fosfomycin and resis clinic. She reports no symptoms and takes no medications. tant to ceftriaxone, ceftazidime. and cefotaxime. Blood cul- On physical examination, vital signs are normal, and tures grow gram-negative rods. flndings are unremarkable. Ceftriaxone is discontinued.

Item 5O An 84-year-old woman is evaluated 2 days after hospitaliza- tion for pneumonia. Initial treatment included ceftriaxone and azithromycin, but azithromycin was stopped following a negative urine Legionella antigen test. She is clinically improved and is able to eat and maintain oral hydration. On physical examination, temperature is 37.7 'C (99.9 'F), blood pressure is 126184 mm Hg, pulse rate is B2lmin, and respiration rate is 18imin. Oxygen saturation Which of the following is the most likely cause of this is 98% breathing ambient air. Pulmonary examination infection? reveals crackles in the right lower lung fleld. Laboratory studies show a leukocyte count of 97OOl1:.L (A) Capnocytophaga canimorsus (g.z x10e/L), improved from 15,400/pL (15.4 x 10e/L). (B) Erysipelothrixrhusiopathiae Admission chest radiograph showed a right lower lobe (C) Mycobacterium marinum inflltrate without a pulmonary effusion. (D) Vibrio uulnificus Which of the following is the most appropriate management? (A) Continueceftriaxone Item 53 A 46-year-old woman is hospitalized with pyelonephritis; tr (B) Measure procalcitonin level empiric ceftriaxone is initiated. Medical history is significant for two urinary tract infections in the previous 15 months (C) Repeat chest radiography treated with ciprofloxacin; her last infection 3 months ago (D) Switch to oral amoxicillin was caused by Escherichia coli resistant to ampicillin and cephalexin. She takes no other medications. On physical examination. temperature is 38.4 "C Item 51 (fOt.Z "F), blood pressure is 105/70 mm Hg, pulse rate is A 2O-year-old woman undergoes follow-up consultation. 106i min, and respiration rate is 2llmin. She has left flank She developed an 8-mm induration on tuberculin skin test- tenderness to palpation. ing during a pre-employment physical examination. She Urine culture reveals more than 10s cfu/ml of E. colt will work as a receptionist in a university internal medicine sensitive to cefepime. ertapenem, and fosfomycin and resis clinic. She reports no symptoms and takes no medications. tant to ceftriaxone, ceftazidime. and cefotaxime. Blood cul- On physical examination, vital signs are normal, and tures grow gram-negative rods. flndings are unremarkable. Ceftriaxone is discontinued. Which ofthe following is the most appropriate management? Which of the following is the most appropriate treatment? (A) Chest radiography (A) Cefepime (B) Interferon-y release assay (B) Colistin

Item 5O An 84-year-old woman is evaluated 2 days after hospitaliza- tion for pneumonia. Initial treatment included ceftriaxone and azithromycin, but azithromycin was stopped following a negative urine Legionella antigen test. She is clinically improved and is able to eat and maintain oral hydration. On physical examination, temperature is 37.7 'C (99.9 'F), blood pressure is 126184 mm Hg, pulse rate is B2lmin, and respiration rate is 18imin. Oxygen saturation Which of the following is the most likely cause of this is 98% breathing ambient air. Pulmonary examination infection? reveals crackles in the right lower lung fleld. Laboratory studies show a leukocyte count of 97OOl1:.L (A) Capnocytophaga canimorsus (g.z x10e/L), improved from 15,400/pL (15.4 x 10e/L). (B) Erysipelothrixrhusiopathiae Admission chest radiograph showed a right lower lobe (C) Mycobacterium marinum inflltrate without a pulmonary effusion. (D) Vibrio uulnificus Which of the following is the most appropriate management? (A) Continueceftriaxone Item 53 A 46-year-old woman is hospitalized with pyelonephritis; tr (B) Measure procalcitonin level empiric ceftriaxone is initiated. Medical history is significant for two urinary tract infections in the previous 15 months (C) Repeat chest radiography treated with ciprofloxacin; her last infection 3 months ago (D) Switch to oral amoxicillin was caused by Escherichia coli resistant to ampicillin and cephalexin. She takes no other medications. On physical examination. temperature is 38.4 "C Item 51 (fOt.Z "F), blood pressure is 105/70 mm Hg, pulse rate is A 2O-year-old woman undergoes follow-up consultation. 106i min, and respiration rate is 2llmin. She has left flank She developed an 8-mm induration on tuberculin skin test- tenderness to palpation. ing during a pre-employment physical examination. She Urine culture reveals more than 10s cfu/ml of E. colt will work as a receptionist in a university internal medicine sensitive to cefepime. ertapenem, and fosfomycin and resis clinic. She reports no symptoms and takes no medications. tant to ceftriaxone, ceftazidime. and cefotaxime. Blood cul- On physical examination, vital signs are normal, and tures grow gram-negative rods. flndings are unremarkable. Ceftriaxone is discontinued. Which ofthe following is the most appropriate management? Which of the following is the most appropriate treatment? (A) Chest radiography (A) Cefepime (B) Interferon-y release assay (B) Colistin 124

Self-Assessment Test +, UI c, tr CONT. (C) Ertapenem (D) Fosfomycin Item 55 A 19-year-old man is evaluated for a 3-day history of 1- +) F q, fever, sore throat, and fatigue without cough. He is not E sexually active. A11 vaccines are current. He takes no tt UI Item 54 medications. q, tt UI A 68-year-old man is hospitalized following a seizure. On physical examination, temperature is 38 "C I Symptoms of fever, chills, dark urine, and headache began (fOO.+ 'F), blood pressure is l24l7O mm Hg, pulse rate is when he returned from a 3-week trip to Malaysia, Laos, 110/min, and respiration rate is 16lmin. Cervical lymph =a, rr! and Cambodia. He is adherent to a mefloquine chemopro- nodes are tender and swollen bilaterally. Pharyngeal ery- phylactic malaria regimen. Medical history is signiflcant for thema is noted but no tonsillar exudate. The spleen tip is splenectomy at age 12 years following a bicycle accident. He palpable. takes no other medications. A rapid Streptococcus paogenes antigen test is On physical examination, the patient is confused. Tem- negative. perature is 39.8 'C (103.6 'F), blood pressure is 92158 mm Hg, pulse rate is 92lmin, and respiration rate is 2Olmin. Which of the following is the most likely cause of this Neurologic examination is nonfocal. Cardiopulmonary patient's illness? examination reveals crackles at the lung bases. (A) Acute HIV infection laboratory studies: Hematocrit 23% (B) Corgnebacterium diphtheriae Bilirubin, total 3.1mg/dl (s3 pmol/L) (C) Epstein-Barr virus Creatinine 2.9 mgldL (2s6 pmol/L) (D) Group A Streptococcus pAogenes Electrolytes Sodium t29 mEqlL (129 mmol/L) Potassium 5 mEq/L (s mmol/L) Item 56 Bicarbonate 18 mEq/L (rs mmol/L) Glucose 51mg/dl (2.8 mmol/L) A 77-year-old man arrives for pretravel consultation. He Urinalysis Leukocytes: 0-5/hpf, erythrocytes: is leaving in 3 weeks for the Democratic Republic of the O-2lhpf,3+blood Congo and plans to spend 10 days there. Medical history Arterial blood gas pH7.l, Pcor 3l mm Hg (4.1kPa), is signiflcant for chronic myeloid leukemia, for which (ambient air) Por75 mm Hg (fo t<Pa) he underwent allogeneic hematopoietic stem cell trans- plantation 2 months ago. His posttransplant course has Peripheral blood smear is shown. been without infection or complications. He is up to date on routine recommended vaccinations. Pretransplant screening showed immunity to varicella-zoster virus and hepatitis B but not to hepatitis A. Medications are predni- sone, tacrolimus, mycophenolate mofetil, acyclovir, and trimethoprim-sulfamethoxazole. Advice about travelers' diarrhea and appropri- ate prophylaxis for travelers' diarrhea and malaria is

+, UI c, tr CONT. (C) Ertapenem (D) Fosfomycin Item 55 A 19-year-old man is evaluated for a 3-day history of 1- +) F q, fever, sore throat, and fatigue without cough. He is not E sexually active. A11 vaccines are current. He takes no tt UI Item 54 medications. q, tt UI A 68-year-old man is hospitalized following a seizure. On physical examination, temperature is 38 "C I Symptoms of fever, chills, dark urine, and headache began (fOO.+ 'F), blood pressure is l24l7O mm Hg, pulse rate is when he returned from a 3-week trip to Malaysia, Laos, 110/min, and respiration rate is 16lmin. Cervical lymph =a, rr! and Cambodia. He is adherent to a mefloquine chemopro- nodes are tender and swollen bilaterally. Pharyngeal ery- phylactic malaria regimen. Medical history is signiflcant for thema is noted but no tonsillar exudate. The spleen tip is splenectomy at age 12 years following a bicycle accident. He palpable. takes no other medications. A rapid Streptococcus paogenes antigen test is On physical examination, the patient is confused. Tem- negative. perature is 39.8 'C (103.6 'F), blood pressure is 92158 mm Hg, pulse rate is 92lmin, and respiration rate is 2Olmin. Which of the following is the most likely cause of this Neurologic examination is nonfocal. Cardiopulmonary patient's illness? examination reveals crackles at the lung bases. (A) Acute HIV infection laboratory studies: Hematocrit 23% (B) Corgnebacterium diphtheriae Bilirubin, total 3.1mg/dl (s3 pmol/L) (C) Epstein-Barr virus Creatinine 2.9 mgldL (2s6 pmol/L) (D) Group A Streptococcus pAogenes Electrolytes Sodium t29 mEqlL (129 mmol/L) Potassium 5 mEq/L (s mmol/L) Item 56 Bicarbonate 18 mEq/L (rs mmol/L) Glucose 51mg/dl (2.8 mmol/L) A 77-year-old man arrives for pretravel consultation. He Urinalysis Leukocytes: 0-5/hpf, erythrocytes: is leaving in 3 weeks for the Democratic Republic of the O-2lhpf,3+blood Congo and plans to spend 10 days there. Medical history Arterial blood gas pH7.l, Pcor 3l mm Hg (4.1kPa), is signiflcant for chronic myeloid leukemia, for which (ambient air) Por75 mm Hg (fo t<Pa) he underwent allogeneic hematopoietic stem cell trans- plantation 2 months ago. His posttransplant course has Peripheral blood smear is shown. been without infection or complications. He is up to date on routine recommended vaccinations. Pretransplant screening showed immunity to varicella-zoster virus and hepatitis B but not to hepatitis A. Medications are predni- sone, tacrolimus, mycophenolate mofetil, acyclovir, and trimethoprim-sulfamethoxazole. Advice about travelers' diarrhea and appropri- ate prophylaxis for travelers' diarrhea and malaria is r$a. - "er provided.

+, UI c, tr CONT. (C) Ertapenem (D) Fosfomycin Item 55 A 19-year-old man is evaluated for a 3-day history of 1- +) F q, fever, sore throat, and fatigue without cough. He is not E sexually active. A11 vaccines are current. He takes no tt UI Item 54 medications. q, tt UI A 68-year-old man is hospitalized following a seizure. On physical examination, temperature is 38 "C I Symptoms of fever, chills, dark urine, and headache began (fOO.+ 'F), blood pressure is l24l7O mm Hg, pulse rate is when he returned from a 3-week trip to Malaysia, Laos, 110/min, and respiration rate is 16lmin. Cervical lymph =a, rr! and Cambodia. He is adherent to a mefloquine chemopro- nodes are tender and swollen bilaterally. Pharyngeal ery- phylactic malaria regimen. Medical history is signiflcant for thema is noted but no tonsillar exudate. The spleen tip is splenectomy at age 12 years following a bicycle accident. He palpable. takes no other medications. A rapid Streptococcus paogenes antigen test is On physical examination, the patient is confused. Tem- negative. perature is 39.8 'C (103.6 'F), blood pressure is 92158 mm Hg, pulse rate is 92lmin, and respiration rate is 2Olmin. Which of the following is the most likely cause of this Neurologic examination is nonfocal. Cardiopulmonary patient's illness? examination reveals crackles at the lung bases. (A) Acute HIV infection laboratory studies: Hematocrit 23% (B) Corgnebacterium diphtheriae Bilirubin, total 3.1mg/dl (s3 pmol/L) (C) Epstein-Barr virus Creatinine 2.9 mgldL (2s6 pmol/L) (D) Group A Streptococcus pAogenes Electrolytes Sodium t29 mEqlL (129 mmol/L) Potassium 5 mEq/L (s mmol/L) Item 56 Bicarbonate 18 mEq/L (rs mmol/L) Glucose 51mg/dl (2.8 mmol/L) A 77-year-old man arrives for pretravel consultation. He Urinalysis Leukocytes: 0-5/hpf, erythrocytes: is leaving in 3 weeks for the Democratic Republic of the O-2lhpf,3+blood Congo and plans to spend 10 days there. Medical history Arterial blood gas pH7.l, Pcor 3l mm Hg (4.1kPa), is signiflcant for chronic myeloid leukemia, for which (ambient air) Por75 mm Hg (fo t<Pa) he underwent allogeneic hematopoietic stem cell trans- plantation 2 months ago. His posttransplant course has Peripheral blood smear is shown. been without infection or complications. He is up to date on routine recommended vaccinations. Pretransplant screening showed immunity to varicella-zoster virus and hepatitis B but not to hepatitis A. Medications are predni- sone, tacrolimus, mycophenolate mofetil, acyclovir, and trimethoprim-sulfamethoxazole. Advice about travelers' diarrhea and appropri- ate prophylaxis for travelers' diarrhea and malaria is r$a. - "er provided. lS;^l$"rFs&I"- -f, i, rsH 3_.cf} Which of the following is the most appropriate additional travel-related infection prophylaxis? 3- . *;€ hts"^a (A) Hepatitis A and capsular polysaccharide typhoid vaccines (B) Dengue and cholera vaccines

lS;^l$"rFs&I"- -f, i, rsH 3_.cf} Which of the following is the most appropriate additional travel-related infection prophylaxis? 3- . *;€ hts"^a (A) Hepatitis A and capsular polysaccharide typhoid vaccines (B) Dengue and cholera vaccines knBffi (C) Measles (rubeola) vaccine and immune globulin (D) Yellow fever and live-attenuated typhoid vaccines A chest radiograph shows pulmonary vascular con- gestion. Item 57 Mefloquine is discontinued. A 29-year-old man is evaluated for a 2 day history of diarrhea and crampy abdominal pain. Medical history is In addition to supportive care, which of the following is signiflcant for non-Hodgkin lymphoma. Medications are the most appropriate treatment? rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone. (A) Artesunate On physical examination, temperature is 38 oC (B) Atovaquone-proguanil (roo.+ 'F); other vital signs are normal. The abdomen is (C) Primaquine nondistended, bowel sounds are present, and mild tender- (D) Tafenoquine ness to palpation is elicited. 125

Self-Assessment Test tr o -+r I A complete blood count and metabolic panel are nor- (C) Cefepime, vancomycin, azithromycin, and mica- tn mal. Rapid molecular gastrointestinal assay of the stool fungin ur identifles Campylobacter. (D) Ceftaroline and azithromycin (D ut UI J (D Which of the following is the most appropriate empiric J treatment for this patient? Item 5O -D -l (D (A) Amoxicillin A 19 year-old woman presents to the student health UI att (B) Azithromycin center to establish care. She reports four male sexual partners over the past year with inconsistent condom (C) Fidaxomicin use. She was diagnosed with chlamydia at age 18 years; (D) Metronidazole she has not been screened for sexually transmitted (E) Vancomycin infections since that time. She is up to date on all rec- ommended vaccinations. Her only medication is an oral contraceptive. Item 58 On physical examination, vital signs and physical A 3S-year-old man is evaluated in the emergency depart- examination are normal. ment for a 3 day history of fever, abdominal pain, and bloody diarrhea but no nausea or vomiting. Medical his- Which of the following sexually transmitted diseases tory is signiflcant for end-stage liver disease secondary to should the patient be screened for now? nonalcoholic steatohepatitis for which he received a liver transplant 4 months ago. Medications are mycophenolate, (A) Chlamydia prednisone, and tacrolimus. (B) Chlamydia, gonorrhea, HIV On physical examination, temperature is 38.6 "C (C) Chlamydia, gonorrhea, HIV, herpes simplex virus (tOf .S 'F), blood pressure is 98164 mm Hg, pulse rate is (D) Chlamydia, gonorrhea, HIV, syphilis I22lmin, and respiration rate is lT lmin. The lungs are clear. The abdomen is distended with diffuse tenderness but no guarding or hepatosplenomegaly. The remainder of the examination is unremarkable. Item 61 A 29-year-old woman is evaluated for multiple episodes of tr diarrhea and emesis with significant abdominal pain and Which of the following viruses is the most likely cause of distension. She was hospitalized 3 days ago for Escherichia the patient's illness? coli-associated pyelonephritis and treated with ceftriaxone. (A) Cytomegalovirus She takes no other medications. (B) Epstein Barr virus On physical examination, the patient is confused. Tem- perature is 38.5 'C (101.3 "F), blood pressure is 90/60 mm (C) Herpes simplex virus type 2 Hg, pulse rate is L25lmin, and respiration rate is 24lmin.The (D) Polyoma BK virus abdomen is distended, with decreased bowel sounds and tenderness to palpation but no guarding. The remainder of the examination is noncontributory. tr Item 59 A S5-year-old woman is admitted to the ICU with acute Laboratory studies show a leukocyte count of 30,000/pL (gO x LOeIL), a serum creatinine level of Z mgldL (177 respiratory failure following a2-day history of fever, cough, pmol/L), and plasma lactate level of 4 mEq/L (a mmol/L). and shortness of breath. She required prolonged hospital- Stool testing for Closfridioides dfficile is positive. ization in the ICU 10 months ago following a motor vehicle Imaging of the colon reveals areas of the large bowel accident. During that time, she was treated with ciproflox- exceeding 6 cm in diameter, consistent with megacolon. acin for Pseudomonos hospital-acquired pneumonia. She The patient is transferred to the ICU and surgical con- takes no medications. sultation is obtained. On physical examination, the patient is intubated and mechanically ventilated. Temperature is 39.2 'C (102.6 'F), Which of the following is the most appropriate initial blood pressure is1O2l64 mm Hg, pulse rate is 120i min, and treatment? respiration rate is 18/min. Oxygen saturation is 94% with a positive end-expiratory pressure of 10 cm HrO, and an Fro, (A) Fecal microbiota transplant of 0.5. Crackles are heard at the lung bases bilaterally. (B) Intravenous vancomycin Gram stain of endotracheal tube aspirate shows mod- (C) Oral vancomycin erate leukocytes, moderate gram-negative rods, and some yeast. COVID-19 testing is negative. (D) Oral metronidazole Chest radiograph shows bilateral opacities. (E) Oral vancomycin plus intravenous metronidazole

tr o -+r I A complete blood count and metabolic panel are nor- (C) Cefepime, vancomycin, azithromycin, and mica- tn mal. Rapid molecular gastrointestinal assay of the stool fungin ur identifles Campylobacter. (D) Ceftaroline and azithromycin (D ut UI J (D Which of the following is the most appropriate empiric J treatment for this patient? Item 5O -D -l (D (A) Amoxicillin A 19 year-old woman presents to the student health UI att (B) Azithromycin center to establish care. She reports four male sexual partners over the past year with inconsistent condom (C) Fidaxomicin use. She was diagnosed with chlamydia at age 18 years; (D) Metronidazole she has not been screened for sexually transmitted (E) Vancomycin infections since that time. She is up to date on all rec- ommended vaccinations. Her only medication is an oral contraceptive. Item 58 On physical examination, vital signs and physical A 3S-year-old man is evaluated in the emergency depart- examination are normal. ment for a 3 day history of fever, abdominal pain, and bloody diarrhea but no nausea or vomiting. Medical his- Which of the following sexually transmitted diseases tory is signiflcant for end-stage liver disease secondary to should the patient be screened for now? nonalcoholic steatohepatitis for which he received a liver transplant 4 months ago. Medications are mycophenolate, (A) Chlamydia prednisone, and tacrolimus. (B) Chlamydia, gonorrhea, HIV On physical examination, temperature is 38.6 "C (C) Chlamydia, gonorrhea, HIV, herpes simplex virus (tOf .S 'F), blood pressure is 98164 mm Hg, pulse rate is (D) Chlamydia, gonorrhea, HIV, syphilis I22lmin, and respiration rate is lT lmin. The lungs are clear. The abdomen is distended with diffuse tenderness but no guarding or hepatosplenomegaly. The remainder of the examination is unremarkable. Item 61 A 29-year-old woman is evaluated for multiple episodes of tr diarrhea and emesis with significant abdominal pain and Which of the following viruses is the most likely cause of distension. She was hospitalized 3 days ago for Escherichia the patient's illness? coli-associated pyelonephritis and treated with ceftriaxone. (A) Cytomegalovirus She takes no other medications. (B) Epstein Barr virus On physical examination, the patient is confused. Tem- perature is 38.5 'C (101.3 "F), blood pressure is 90/60 mm (C) Herpes simplex virus type 2 Hg, pulse rate is L25lmin, and respiration rate is 24lmin.The (D) Polyoma BK virus abdomen is distended, with decreased bowel sounds and tenderness to palpation but no guarding. The remainder of the examination is noncontributory. tr Item 59 A S5-year-old woman is admitted to the ICU with acute Laboratory studies show a leukocyte count of 30,000/pL (gO x LOeIL), a serum creatinine level of Z mgldL (177 respiratory failure following a2-day history of fever, cough, pmol/L), and plasma lactate level of 4 mEq/L (a mmol/L). and shortness of breath. She required prolonged hospital- Stool testing for Closfridioides dfficile is positive. ization in the ICU 10 months ago following a motor vehicle Imaging of the colon reveals areas of the large bowel accident. During that time, she was treated with ciproflox- exceeding 6 cm in diameter, consistent with megacolon. acin for Pseudomonos hospital-acquired pneumonia. She The patient is transferred to the ICU and surgical con- takes no medications. sultation is obtained. On physical examination, the patient is intubated and mechanically ventilated. Temperature is 39.2 'C (102.6 'F), Which of the following is the most appropriate initial blood pressure is1O2l64 mm Hg, pulse rate is 120i min, and treatment? respiration rate is 18/min. Oxygen saturation is 94% with a positive end-expiratory pressure of 10 cm HrO, and an Fro, (A) Fecal microbiota transplant of 0.5. Crackles are heard at the lung bases bilaterally. (B) Intravenous vancomycin Gram stain of endotracheal tube aspirate shows mod- (C) Oral vancomycin erate leukocytes, moderate gram-negative rods, and some yeast. COVID-19 testing is negative. (D) Oral metronidazole Chest radiograph shows bilateral opacities. (E) Oral vancomycin plus intravenous metronidazole Which of the following is the most appropriate initial antimicrobial treatment? (A) Cefepime and levofloxacin Item 62 A 78-year-old man is evaluated in the emergency depart- tr ment for a l-week history of fever, confusion, and altered (B) Cefepime, vancomycin, and levofloxacin speech. Medical history is otherwise unremarkable.

Which of the following is the most appropriate initial antimicrobial treatment? (A) Cefepime and levofloxacin Item 62 A 78-year-old man is evaluated in the emergency depart- tr ment for a l-week history of fever, confusion, and altered (B) Cefepime, vancomycin, and levofloxacin speech. Medical history is otherwise unremarkable. 126

Self-Assessment Test +t UI On physical examination, temperature is 39.5 oC o, m 3 months after transplantation. Medications are tacrolimus, F lI (tOa.1 "F); othervital signs are normal. The patient is difficult prednisone, mycophenolate mofetil, and trimethoprim, P ? c0NT' to rouse, is disoriented, and cannot follow commands. The (u sulfamethoxazole. ? F neurologic examination is nonfocal, and the remainder of On physical examination, temperature is 37.3 "C |a the physical examination is normal. (OO.t "F); other vital signs are normal. The abdomen is ten- Ut (u Empiric intravenous vancomycin, ampicillin, ceftriax- tl der in the lower quadrants, but no guarding is noted. The Ul one, and acyclovir are initiated. remainder of the examination is unremarkable. rtsa

+t UI On physical examination, temperature is 39.5 oC o, m 3 months after transplantation. Medications are tacrolimus, F lI (tOa.1 "F); othervital signs are normal. The patient is difficult prednisone, mycophenolate mofetil, and trimethoprim, P ? c0NT' to rouse, is disoriented, and cannot follow commands. The (u sulfamethoxazole. ? F neurologic examination is nonfocal, and the remainder of On physical examination, temperature is 37.3 "C |a the physical examination is normal. (OO.t "F); other vital signs are normal. The abdomen is ten- Ut (u Empiric intravenous vancomycin, ampicillin, ceftriax- tl der in the lower quadrants, but no guarding is noted. The Ul one, and acyclovir are initiated. remainder of the examination is unremarkable. rtsa Crrebrospinal fluid studies: Colonoscopy biopsy specimens reveal cytopathic -rrl(l, Leukocyte count 60l1tL (OO x tOo/L)with 88% "owl's-eye" intracellular inclusions. Tissue culture is pending. lymphocytes Glucose 42mgldL (2.3 mmol/L) Which of the following is the most appropriate Protein 113 mg/dl (ttsO mg/L) treatment? Gram stain and culture Negative (A) cidofovir Multiplex polymerase chain reaction assay of the cere- (B) Foscarnet brospinal fluid for viruses and bacteria is negative. (C) Letermovir MRI of the brain is shown. (D) Valganciclovir

Crrebrospinal fluid studies: Colonoscopy biopsy specimens reveal cytopathic -rrl(l, Leukocyte count 60l1tL (OO x tOo/L)with 88% "owl's-eye" intracellular inclusions. Tissue culture is pending. lymphocytes Glucose 42mgldL (2.3 mmol/L) Which of the following is the most appropriate Protein 113 mg/dl (ttsO mg/L) treatment? Gram stain and culture Negative (A) cidofovir Multiplex polymerase chain reaction assay of the cere- (B) Foscarnet brospinal fluid for viruses and bacteria is negative. (C) Letermovir MRI of the brain is shown. (D) Valganciclovir Item 54 A 2S-year old woman is evaluated in December for a2-day history of cough, fever, and sore throat. She has a 4-year-old son who had similar symptoms 10 days ago. She received the quadrivalent influenza vaccine 2 months ago. She takes no medications. On physical examination, temperature is 38.2 'C (1OO.S 'F), blood pressure is 104/68 mm Hg, pulse rate is 82imin, and respiration rate is 20/min. Pulmonary exam- ination reveals decreased breath sounds in the right lung base. COVID-19 testing is negative. A chest radiograph shows a right lower lobe inflltrate.

Item 54 A 2S-year old woman is evaluated in December for a2-day history of cough, fever, and sore throat. She has a 4-year-old son who had similar symptoms 10 days ago. She received the quadrivalent influenza vaccine 2 months ago. She takes no medications. On physical examination, temperature is 38.2 'C (1OO.S 'F), blood pressure is 104/68 mm Hg, pulse rate is 82imin, and respiration rate is 20/min. Pulmonary exam- ination reveals decreased breath sounds in the right lung base. COVID-19 testing is negative. A chest radiograph shows a right lower lobe inflltrate. Which of the following is the most appropriate diagnostic test to perform next? (A) Procalcitoninlevel (B) Rapid influenza antigen test (C) Rapid influenza nucleic acid ampliflcation test (D) Sputum Gram stain and culture

Which of the following is the most appropriate diagnostic test to perform next? (A) Procalcitoninlevel (B) Rapid influenza antigen test (C) Rapid influenza nucleic acid ampliflcation test (D) Sputum Gram stain and culture Item 55 Which of the following is the most appropriate A 39-year old man is seen in a follow-up visit for an intravenous treatment? 8-week history of intermittent and fluctuating fevers (A) Continue antibiotics and acyclovir that began after returning from Guyana 2 months ago. He also reports fatigue; muscle, bone, and joint aches; (B) Continue antibiotics and discontinue acyciovir and depression. During his trip, he ate and slept in rural (C) Discontinue antibiotics and continue acyclovir villages. He was adherent to his tafenoquine malaria (D) Discontinue current medications and start immune prophylaxis. globulin and glucocorticoids On physical examination, temperature is 37.5 'C (gg.S 'F); other vital signs are normal. Scattered lymphade- nopathy is noted. The liver edge is palpable 2 cm below the

Item 55 Which of the following is the most appropriate A 39-year old man is seen in a follow-up visit for an intravenous treatment? 8-week history of intermittent and fluctuating fevers (A) Continue antibiotics and acyclovir that began after returning from Guyana 2 months ago. He also reports fatigue; muscle, bone, and joint aches; (B) Continue antibiotics and discontinue acyciovir and depression. During his trip, he ate and slept in rural (C) Discontinue antibiotics and continue acyclovir villages. He was adherent to his tafenoquine malaria (D) Discontinue current medications and start immune prophylaxis. globulin and glucocorticoids On physical examination, temperature is 37.5 'C (gg.S 'F); other vital signs are normal. Scattered lymphade- nopathy is noted. The liver edge is palpable 2 cm below the tr Item 63 A46-year-old woman is evaluated for abdominal pain, diar- rib cage. Low back discomfort is elicited with flexion and distension. The remainder of the examination is normal. rhea, and low-grade fever of l week's duration. She under- Laboratory studies obtained 5 days ago: went kidney transplantation 4 months ago for end-stage Hematocrit 33"/. kidney disease resulting from autosomal dominant poly- Leukocyte count SaOOlltL (a.+ x IOe IL) cystic kidney disease. She is cytomegalovirus seronegative Alkaline phosphatase 167 U lL and received an organ from a cytomegalovirus seroposi- Alanine aminotransferase 7lUlL tive donor; she received cfiomegalovirus prophylaxis for Aspartate aminotransferase 46UlL 127

Self-Assessment Test vt (D -D - Ih Blood cultures are negative. Urinalysis is normal. HIV serology, interferon y t/t Chest radiograph is normal. Abdominal ultrasound release assay, rheumatoid factor, and antinuclear antibody r/t shows hepatosplenomegaly. test results are negative. Three sets of blood cultures are (D UI negative. UI J .J Which of the following is the most likely diagnosis? A chest radiograph is normal, and CT scan of the abdo- .D men and pelvis with and without contrast is unremarkable. J (A) Brucellosis { rit

vt (D -D - Ih Blood cultures are negative. Urinalysis is normal. HIV serology, interferon y t/t Chest radiograph is normal. Abdominal ultrasound release assay, rheumatoid factor, and antinuclear antibody r/t shows hepatosplenomegaly. test results are negative. Three sets of blood cultures are (D UI negative. UI J .J Which of the following is the most likely diagnosis? A chest radiograph is normal, and CT scan of the abdo- .D men and pelvis with and without contrast is unremarkable. J (A) Brucellosis { rit (D (B) Coxiella infection (Q fever) UI Which of the following is the most appropriate e+ (C) Histoplasmosis management? (D) Malaria (A) Bone marrow biopsy (B) Empiric trial of systemic glucocorticoids (C) Liver biopsy tr Item 66 A 32-year old man is hospitalized fbr;r 2 week history ot' (D) Clinicalobservation gradually worsening headache and f'ever. He was diagnosecl with HIV infection 1 month ago. but he has yet to initiate antiretroviral therapy. Medical history is otherwise noncon Item 68 tributory. and he takes no meclications. A 22-year-old man is hospitalized with a 3-day history On physical examination. the patient is lethargic but of nonproductive cough, fever, and diarrhea. He returned responds appropriately to qllestions. Temperature is 38.l 'C 1 week ago from a tournament in Indiana with his college (100.5 oF): other vital signs are normal. White plaques trre wrestling team. During this trip, the team used an indoor present on the palate and bucc;rl mucosa. hot tub. Three other team members have developed a flu- Laboratory studies sholr,a positive serum cryptococcrrl like illness. Medical history is noncontributory, and he takes lntigen test result of 1:256. I IIV viral load of 95.640 copies, no medications. m[,. and CD4 cell count of'42rtrl. On physical examination, temperature is 38.8 'C A noncontrast CT scan of the heird is negative. (tOt.A 'F), blood pressure is 115/75 mm Hg, pulse rate is Intravenous liposomal irmphotericin-B and oral flncy- 68/min, and respiration rate is 24lmin. The examination tosine are initiated. is unremarkable. Laboratory studies show a serum sodium level of Which of the following is the most appropriate next step in 128 mEq/L (rzA mmolil). the management of this patient? COVID-19 testing and Legionella urinary antigen are negative. (A) Add fluconazole A chest radiograph is shown. (B) Perlbrm lumbar puncture (C) Start abacavir-lamivudine-dolutegrervir (D) St;rrt tenofovir-emtricitabine dolutegravir

(D (B) Coxiella infection (Q fever) UI Which of the following is the most appropriate e+ (C) Histoplasmosis management? (D) Malaria (A) Bone marrow biopsy (B) Empiric trial of systemic glucocorticoids (C) Liver biopsy tr Item 66 A 32-year old man is hospitalized fbr;r 2 week history ot' (D) Clinicalobservation gradually worsening headache and f'ever. He was diagnosecl with HIV infection 1 month ago. but he has yet to initiate antiretroviral therapy. Medical history is otherwise noncon Item 68 tributory. and he takes no meclications. A 22-year-old man is hospitalized with a 3-day history On physical examination. the patient is lethargic but of nonproductive cough, fever, and diarrhea. He returned responds appropriately to qllestions. Temperature is 38.l 'C 1 week ago from a tournament in Indiana with his college (100.5 oF): other vital signs are normal. White plaques trre wrestling team. During this trip, the team used an indoor present on the palate and bucc;rl mucosa. hot tub. Three other team members have developed a flu- Laboratory studies sholr,a positive serum cryptococcrrl like illness. Medical history is noncontributory, and he takes lntigen test result of 1:256. I IIV viral load of 95.640 copies, no medications. m[,. and CD4 cell count of'42rtrl. On physical examination, temperature is 38.8 'C A noncontrast CT scan of the heird is negative. (tOt.A 'F), blood pressure is 115/75 mm Hg, pulse rate is Intravenous liposomal irmphotericin-B and oral flncy- 68/min, and respiration rate is 24lmin. The examination tosine are initiated. is unremarkable. Laboratory studies show a serum sodium level of Which of the following is the most appropriate next step in 128 mEq/L (rzA mmolil). the management of this patient? COVID-19 testing and Legionella urinary antigen are negative. (A) Add fluconazole A chest radiograph is shown. (B) Perlbrm lumbar puncture (C) Start abacavir-lamivudine-dolutegrervir (D) St;rrt tenofovir-emtricitabine dolutegravir Item 67 A S2-year old man undergoes follow-up evaluation after initial testing for fevers up to 38.4 "C (fOf.Z oF) recurring over the past B weeks. He has no other symptoms. His weight has been stable, and he continues to work. He has never traveled outside the United States; reports no tick or insect bites or animal exposures; and does not consume raw meat, raw seafood, or unpasteurized dairy products. On physical examination, temperature is 37.8 "C (100 "F), blood pressure is 116174 mm Hg, pulse rate is 84/min, and respiration rate is 16/min. The examination is unremarkable. Laboratory studies: Erythrocyte sedimentation 12mmlh rate Hematocrit 44"/,, The patient improves within 48 hours of initiating Leukocyte count 8800/pL (S.g x 10e/L), with empiric therapy with ceftriaxone and azithromycin. normal differential Platelet count 279,OOOI1tL (279 xt}e IL) Which of the following is the most likely diagnosis? Alkaline phosphatase Normal Lactate dehydrogenase Normal (A) Herpes simplex virus type l pneumonia Liver chemistry tests Normal (B) Histoplosmopneumonia Kidney function tests Normal (C) Legionellapneumonia

Item 67 A S2-year old man undergoes follow-up evaluation after initial testing for fevers up to 38.4 "C (fOf.Z oF) recurring over the past B weeks. He has no other symptoms. His weight has been stable, and he continues to work. He has never traveled outside the United States; reports no tick or insect bites or animal exposures; and does not consume raw meat, raw seafood, or unpasteurized dairy products. On physical examination, temperature is 37.8 "C (100 "F), blood pressure is 116174 mm Hg, pulse rate is 84/min, and respiration rate is 16/min. The examination is unremarkable. Laboratory studies: Erythrocyte sedimentation 12mmlh rate Hematocrit 44"/,, The patient improves within 48 hours of initiating Leukocyte count 8800/pL (S.g x 10e/L), with empiric therapy with ceftriaxone and azithromycin. normal differential Platelet count 279,OOOI1tL (279 xt}e IL) Which of the following is the most likely diagnosis? Alkaline phosphatase Normal Lactate dehydrogenase Normal (A) Herpes simplex virus type l pneumonia Liver chemistry tests Normal (B) Histoplosmopneumonia Kidney function tests Normal (C) Legionellapneumonia 128

Self-Assessment Test f vt (D) Mycobacterium auiumcomplex lung infection Blood cultures from admission remain negative F G' (E) Pseudomonospneumonia f E Which of the following is the most likely diagnosis? a, E UI (A) Brucellosis UI Item 69 o, (B) Ehrlichiosis UI (,t A S5-year-old man is evaluated for fever, night sweats, (C) Heartland virus infection g-I cough with sputum production, and a 6.8-kg (tS tU) weight loss over the past 2 months. He was diagnosed with HIV (D) Rocky Mountain spotted fever E yr infection 3 months ago but has not started antiretroviral therapy. He has a history of alcohol use disorder and was incarcerated 5 years ago. Item 71 On physical examination, temperature is 38.4 .C A 62-year-old man is evaluated for a 1-week history of (tOt.t 'F); other vital signs are normal. Crackles are heard burning pain and a rash over the chest and low back. Med- bilaterally in the lung bases. ical history is notable for idiopathic pulmonary flbrosis and Iaboratory studies: a single lung transplantation 3 years ago. Medications are Hemoglobin tacrolimus, mycophenolate, and prednisone. 10 g/dl (rOO git-) Leukocyte count On physical examination, vital signs are normal. Vesic- 11,500/pL (tt.S x 10e/L) HIV antigeni antibody Positive ular lesions on an erythematous base are densely present combination assay in several dermatomes on the right posterior and anterior CD4 cell count thorax and lumbar areas. 2OOlptL The patient is admitted to the hospital with contact and Viral load 56,000 copies/ml airborne precautions. Polymerase chain reaction testing for Chest radiograph shows paratracheal lymphade- varicella-zoster virus is pending. nopathy and bilateral interstitial inflltrates. Sputum Gram stain and cultures are negative. Acid-fast Which of the following is the most appropriate additional bacilli stain is positive;yeasts are not identified. management?

f vt (D) Mycobacterium auiumcomplex lung infection Blood cultures from admission remain negative F G' (E) Pseudomonospneumonia f E Which of the following is the most likely diagnosis? a, E UI (A) Brucellosis UI Item 69 o, (B) Ehrlichiosis UI (,t A S5-year-old man is evaluated for fever, night sweats, (C) Heartland virus infection g-I cough with sputum production, and a 6.8-kg (tS tU) weight loss over the past 2 months. He was diagnosed with HIV (D) Rocky Mountain spotted fever E yr infection 3 months ago but has not started antiretroviral therapy. He has a history of alcohol use disorder and was incarcerated 5 years ago. Item 71 On physical examination, temperature is 38.4 .C A 62-year-old man is evaluated for a 1-week history of (tOt.t 'F); other vital signs are normal. Crackles are heard burning pain and a rash over the chest and low back. Med- bilaterally in the lung bases. ical history is notable for idiopathic pulmonary flbrosis and Iaboratory studies: a single lung transplantation 3 years ago. Medications are Hemoglobin tacrolimus, mycophenolate, and prednisone. 10 g/dl (rOO git-) Leukocyte count On physical examination, vital signs are normal. Vesic- 11,500/pL (tt.S x 10e/L) HIV antigeni antibody Positive ular lesions on an erythematous base are densely present combination assay in several dermatomes on the right posterior and anterior CD4 cell count thorax and lumbar areas. 2OOlptL The patient is admitted to the hospital with contact and Viral load 56,000 copies/ml airborne precautions. Polymerase chain reaction testing for Chest radiograph shows paratracheal lymphade- varicella-zoster virus is pending. nopathy and bilateral interstitial inflltrates. Sputum Gram stain and cultures are negative. Acid-fast Which of the following is the most appropriate additional bacilli stain is positive;yeasts are not identified. management? Which of the following is the most likely cause of his (A) Intravenousacyclovir infection? (B) Oral famciclovir (C) Oral valacyclovir (A) Histoplasma capsulatum (D) Recombinant herpes zoster vaccine (B) Mycobacteriumobscessus (C) Mycobacterium auiumcomplex (D) Mycobacterium tuberculosis Item 7 2 A 29 year-old woman is evaluated for cough and fever of 2 days' duration. She has a history of cystic acne, which is

Which of the following is the most likely cause of his (A) Intravenousacyclovir infection? (B) Oral famciclovir (C) Oral valacyclovir (A) Histoplasma capsulatum (D) Recombinant herpes zoster vaccine (B) Mycobacteriumobscessus (C) Mycobacterium auiumcomplex (D) Mycobacterium tuberculosis Item 7 2 A 29 year-old woman is evaluated for cough and fever of 2 days' duration. She has a history of cystic acne, which is tr Item 70 A S5-year-old man is evaluated in the tCU for low blood treated with a topical retinoid cream and daily minocycline. On physical examination, temperature is 38.3 "C (fOO.g 'F), blood pressure is 110/70 mm Hg, pulse rate is pressure requiring vasopressor support. He was hospital- ized 3 days ago with a 3-day history of fever, headache, 90/min, and respiration rate is 2Oimin. Oxygen saturation and myalgia. He owns a dairy farm in rural Arkansas and is 93% breathing ambient air. Decreased breath sounds are drinks unpasteurized milk. He is an active outdoorsman. heard at the right lung base. On admission to the hospital, temperature was 39.2 oC COVID-19 testing is negative. (lOZ.O "F). pulse rate was 120i min. and other vital signs were A chest radiograph shows a right lower lobe inflltrate. normal. No lymphadenopathy or skin lesions were noted. Empiric doxycycline was initiated on admission; he takes Which of the following is the most appropriate treatment? no other medications. (A) Amoxicillin On physical examination in the ICU, temperature is 38.9 "C (tOZ'F), blood pressure is9Al64 mm Hg, pulse rate (B) Ceftriaxone and azithromycin is 128rmin, and respiration rate is 24lmin. The remainder (C) Cefuroxime and doxycycline of the physical examination is unchanged from admission. (D) Doxycycline Labratory studies: (E) Levofloxacin Admission Hospital Day 3 Leukocytecount 3400lpl 1200ipl (9.+ x loei L) (1.2 x 1o"il) Item 73 Platelet count 110,000,pL 65.000,"prl A S7-year-old man is evaluated for persistent redness and (tto x 1os/L) (os x roeiL) drainage at the site of a puncture wound from a nail he Alanine 79 U L 2O2tJ iL stepped on 17 days ago. He has not responded to initial aminotransferase therapy with cephalexin. Culture obtained 2 days ago is Aspartate 62tJ iL 124 U iL positive for Pseudomonos oeruginoso sensitive to ceftazi- aminotransferase dime, cefepime, piperacillin-tazobactam, and ciprofloxacin.

tr Item 70 A S5-year-old man is evaluated in the tCU for low blood treated with a topical retinoid cream and daily minocycline. On physical examination, temperature is 38.3 "C (fOO.g 'F), blood pressure is 110/70 mm Hg, pulse rate is pressure requiring vasopressor support. He was hospital- ized 3 days ago with a 3-day history of fever, headache, 90/min, and respiration rate is 2Oimin. Oxygen saturation and myalgia. He owns a dairy farm in rural Arkansas and is 93% breathing ambient air. Decreased breath sounds are drinks unpasteurized milk. He is an active outdoorsman. heard at the right lung base. On admission to the hospital, temperature was 39.2 oC COVID-19 testing is negative. (lOZ.O "F). pulse rate was 120i min. and other vital signs were A chest radiograph shows a right lower lobe inflltrate. normal. No lymphadenopathy or skin lesions were noted. Empiric doxycycline was initiated on admission; he takes Which of the following is the most appropriate treatment? no other medications. (A) Amoxicillin On physical examination in the ICU, temperature is 38.9 "C (tOZ'F), blood pressure is9Al64 mm Hg, pulse rate (B) Ceftriaxone and azithromycin is 128rmin, and respiration rate is 24lmin. The remainder (C) Cefuroxime and doxycycline of the physical examination is unchanged from admission. (D) Doxycycline Labratory studies: (E) Levofloxacin Admission Hospital Day 3 Leukocytecount 3400lpl 1200ipl (9.+ x loei L) (1.2 x 1o"il) Item 73 Platelet count 110,000,pL 65.000,"prl A S7-year-old man is evaluated for persistent redness and (tto x 1os/L) (os x roeiL) drainage at the site of a puncture wound from a nail he Alanine 79 U L 2O2tJ iL stepped on 17 days ago. He has not responded to initial aminotransferase therapy with cephalexin. Culture obtained 2 days ago is Aspartate 62tJ iL 124 U iL positive for Pseudomonos oeruginoso sensitive to ceftazi- aminotransferase dime, cefepime, piperacillin-tazobactam, and ciprofloxacin. 129

.l Self-Assessment Test Itt (D +r I A previous radiograph of the left foot showed no evidence of D UI osteomyelitis. Medical history is notable for recurrent par- tt (D oxysmal atrial flbrillation, forwhich he takes amiodarone. Ut On physical examination, vital signs are normal. A l,r small amount of purulent drainage is seen at the puncture (D J wound at the left flrst metatarsophalangeal joint with some { FI (D surrounding erythema. tr Ciprofloxacin will be prescribed. * Which screening activity should take place before treatment? (A) Aminotransferase levels (B) Electrocardiography (C) Lipase level (D) Visual acuity

Itt (D +r I A previous radiograph of the left foot showed no evidence of D UI osteomyelitis. Medical history is notable for recurrent par- tt (D oxysmal atrial flbrillation, forwhich he takes amiodarone. Ut On physical examination, vital signs are normal. A l,r small amount of purulent drainage is seen at the puncture (D J wound at the left flrst metatarsophalangeal joint with some { FI (D surrounding erythema. tr Ciprofloxacin will be prescribed. * Which screening activity should take place before treatment? (A) Aminotransferase levels (B) Electrocardiography (C) Lipase level (D) Visual acuity Item 74 A 4O-year-old man undergoes follow-up after antiretro- viral therapy initiation l year ago when he was diagnosed with HIV infection. A chest radiograph at that time showed no inflltrate. He reports being incarcerated a few years Which of the following CSF tests will confirm the diagnosis ago. Medications are tenofovir alafenamide, emtricitabine, bictegravir, and trimethoprim-sulfamethoxazole. in this patient? On physical examination, vital signs are nornal. He (A) Herpes simplex virus IgM has no cervical lymphadenopathy, and the lungs are clear (B) Herpes simplex virus polymerase chain reaction (PCR) to auscultation. (C) West Nile virus IgM laboratory studies: (D) West Nile virus PCR I YearAgo Current CD4 cell count 56l1tL 2O4l1tL HIV RNA nucleic acid 1,500,000 50 copies/ml Item 76 ampliflcation test copies/mL A S2-year-old woman is evaluated for a l-month history Interferon-y release Negative of fever, malaise, and weight loss. She has a history of car- assay diomyopathy, for which she received a heart transplant Which of the following is the most appropriate 5 years ago; 3 months ago, an episode of rejection occurred, management? and high-dose glucocorticoids were initiated. At the time of transplantation, studies were significant for donor seropositiv- (A) Acid-fast bacilli blood cultures for Mycobacterium ity for Epstein-Barr virus and cytomegalovirus; the patient was au ium complex infection negative for both. Medications are tacrolimus, mycophenolate (B) Active tuberculosis treatment mofetil, prednisone, and trimethoprim-sulfamethox azole. (C) Latent tuberculosis treatment On physical examination, temperature is 37.7 "C (99.9 'F), and other vital signs are normal. Cervical lymph- (D) Interferon-yrelease assay adenopathy is noted. The remainder of the examination is (E) No testing or therapy unremarkable. CT scan of the chest shows an anterior mediastinal mass.

Item 74 A 4O-year-old man undergoes follow-up after antiretro- viral therapy initiation l year ago when he was diagnosed with HIV infection. A chest radiograph at that time showed no inflltrate. He reports being incarcerated a few years Which of the following CSF tests will confirm the diagnosis ago. Medications are tenofovir alafenamide, emtricitabine, bictegravir, and trimethoprim-sulfamethoxazole. in this patient? On physical examination, vital signs are nornal. He (A) Herpes simplex virus IgM has no cervical lymphadenopathy, and the lungs are clear (B) Herpes simplex virus polymerase chain reaction (PCR) to auscultation. (C) West Nile virus IgM laboratory studies: (D) West Nile virus PCR I YearAgo Current CD4 cell count 56l1tL 2O4l1tL HIV RNA nucleic acid 1,500,000 50 copies/ml Item 76 ampliflcation test copies/mL A S2-year-old woman is evaluated for a l-month history Interferon-y release Negative of fever, malaise, and weight loss. She has a history of car- assay diomyopathy, for which she received a heart transplant Which of the following is the most appropriate 5 years ago; 3 months ago, an episode of rejection occurred, management? and high-dose glucocorticoids were initiated. At the time of transplantation, studies were significant for donor seropositiv- (A) Acid-fast bacilli blood cultures for Mycobacterium ity for Epstein-Barr virus and cytomegalovirus; the patient was au ium complex infection negative for both. Medications are tacrolimus, mycophenolate (B) Active tuberculosis treatment mofetil, prednisone, and trimethoprim-sulfamethox azole. (C) Latent tuberculosis treatment On physical examination, temperature is 37.7 "C (99.9 'F), and other vital signs are normal. Cervical lymph- (D) Interferon-yrelease assay adenopathy is noted. The remainder of the examination is (E) No testing or therapy unremarkable. CT scan of the chest shows an anterior mediastinal mass. Item 75 Which of the following infections is the most likely cause A 67 -year-old man is evaluated in the emergency department of the patient's findings? during the summer for confusion, facial tremor, and seizures; (A) Adenovirus he also has a 3-day history of fever, headaches, and a rash. On physical examination, temperature is 39.1 'C (B) Epstein-Barr virus (tOZ.+ oF), blood pressure is 125/98 mm Hg, pulse rate is (C) Escherichia coli l22lmin, and respiration rate is 22lmin. The patient is (D) Pneumocgstis jirouecii obtunded, with a score of 12 on the Glasgow Coma Scale. Left facial tremor and a diffuse maculopapular rash are present. Cerebrospinal fluid (CSF) studies show a leukocyte count of l34l1tL (fg+ x 106/L) with 56% Iymphocytes, glu, cose level of 48 mg/dl (2.7 mmol/L), and protein level of Item 77 A 4S-year-old man is evaluated in the emergency depart- tr ment for new-onset seizures; he also reports a 2-week lI2mgldL (rrzo mglr). history of headaches and right ear drainage. Medical MRI of the brain is shown (top of next column). history is noncontributory, and he takes no medications.

Item 75 Which of the following infections is the most likely cause A 67 -year-old man is evaluated in the emergency department of the patient's findings? during the summer for confusion, facial tremor, and seizures; (A) Adenovirus he also has a 3-day history of fever, headaches, and a rash. On physical examination, temperature is 39.1 'C (B) Epstein-Barr virus (tOZ.+ oF), blood pressure is 125/98 mm Hg, pulse rate is (C) Escherichia coli l22lmin, and respiration rate is 22lmin. The patient is (D) Pneumocgstis jirouecii obtunded, with a score of 12 on the Glasgow Coma Scale. Left facial tremor and a diffuse maculopapular rash are present. Cerebrospinal fluid (CSF) studies show a leukocyte count of l34l1tL (fg+ x 106/L) with 56% Iymphocytes, glu, cose level of 48 mg/dl (2.7 mmol/L), and protein level of Item 77 A 4S-year-old man is evaluated in the emergency depart- tr ment for new-onset seizures; he also reports a 2-week lI2mgldL (rrzo mglr). history of headaches and right ear drainage. Medical MRI of the brain is shown (top of next column). history is noncontributory, and he takes no medications. 130

Self-Assessment Test P UI Fl On physical examination, vital signs are norrnal. puru- (C) MRI (u F lll lent drainage is seen from the right eiternal ear canal. The (D) Triple-phase bone scan P coNI. 696l mastoid is tender. (u CT scan of the head with and without contrast shows ut a 3-cm right temporal ring-enhancing lesion and a right Item 80 UI otomastoiditis. A 24-year-old woman is evaluated in the emergency department during the winter for headache and fever of tr (u l,I l,I r+- a

P UI Fl On physical examination, vital signs are norrnal. puru- (C) MRI (u F lll lent drainage is seen from the right eiternal ear canal. The (D) Triple-phase bone scan P coNI. 696l mastoid is tender. (u CT scan of the head with and without contrast shows ut a 3-cm right temporal ring-enhancing lesion and a right Item 80 UI otomastoiditis. A 24-year-old woman is evaluated in the emergency department during the winter for headache and fever of tr (u l,I l,I r+- a Which of the following is the most appropriate next step in (u 3 days'duration. She lives in Minnesota. Medical history is ttt management? noncontributory, and her only medication is ibuprofen for (A) Intravenous penicillin and metronidazole headaches. (B) Intravenousvancomycin On physical examination, temperature is 3g "C (100.4 "F). (C) Lumbar puncture and culture of cerebrospinal fluid Other vital signs are norrnal. Other than a stiff neck and photophobia, the physical examination is normal. (D) Stereotactic needle aspiration of brain lesion Cerebrospinal fluid studies: Leukocyte count 276/1tL (ZZ0xLO6lL) with 45% neutrophils Item 78 Glucose 44 mg/dL (2.4 mmol/L) A 48-year-old woman is evaluated for an 18-mm indu- Protein 95 mg/dl (esO mgil) ration following tuberculin skin testing performed at her Gram stain Negative request following return from a medical mission in Peru Culture Pending 6 weeks ago. She reports possible exposure to tuberculo- A CT of the head with contrast is normal. sis. A fourth-generation HIV test and pregnancy test are negative. Which of the following is the most likely diagnosis? On physical examination, vital signs are normal, and the examination is unremarkable. (A) Enterovirus Posteroanterior and lateral chest radiographs are (B) Herpes simplex virus type 1 negative. (C) Herpes simplex virus type 2 (D) West Nile virus Which ofthe following is the most appropriate management? (A) Isoniazid, daily for 6 months Item 81 (B) Isoniazid, daily for 9 months A72-year-old man is evaluated for a 2-day history of right (C) Isoniazid and rifampin, daily for 3 months facial drooping and burning pain on the right side of the tongue. He also reports a rash in the right ear. He reports (D) Isoniazid, rifampin, pyrazinamide, and ethambutol no other medical problems and takes no medications. On physical examination, vital signs are norrnal. Vesic- ular and some crusted lesions are seen on the right external Item 79 ear. Right facial palsy that includes the forehead is observed. A SO-year-old man is evaluated in the emergency depart- Tongue flndings are shown. ment for a chronic, nonpainful ulcer on the plantar aspect of his right foot that has recently begun to drain foul-smelling pus. Medical history is notable for type 2 diabetes mellitus and hypertension. Medications are metformin, canagli- flozin, and lisinopril. On physical examination, temperature is 37.9 "C (1OO.Z "F); other vital signs are normal. A 5- x 3-cm plantar ulcer draining pus is present on the right foot at the base of the third metatarsal with associated warmth, edema, and erythema. Right dorsalis pedis pulse is palpable. Bone cannot be visualized, and a metal probe cannot palpate bone. Laboratory studies show an erythrocyte sedimenta- tion rate of 100 mm/h and a leukocyte count of 12,500/pL (rz.s x Loe tL). A plain radiograph of the foot is normal.

Which of the following is the most appropriate next step in (u 3 days'duration. She lives in Minnesota. Medical history is ttt management? noncontributory, and her only medication is ibuprofen for (A) Intravenous penicillin and metronidazole headaches. (B) Intravenousvancomycin On physical examination, temperature is 3g "C (100.4 "F). (C) Lumbar puncture and culture of cerebrospinal fluid Other vital signs are norrnal. Other than a stiff neck and photophobia, the physical examination is normal. (D) Stereotactic needle aspiration of brain lesion Cerebrospinal fluid studies: Leukocyte count 276/1tL (ZZ0xLO6lL) with 45% neutrophils Item 78 Glucose 44 mg/dL (2.4 mmol/L) A 48-year-old woman is evaluated for an 18-mm indu- Protein 95 mg/dl (esO mgil) ration following tuberculin skin testing performed at her Gram stain Negative request following return from a medical mission in Peru Culture Pending 6 weeks ago. She reports possible exposure to tuberculo- A CT of the head with contrast is normal. sis. A fourth-generation HIV test and pregnancy test are negative. Which of the following is the most likely diagnosis? On physical examination, vital signs are normal, and the examination is unremarkable. (A) Enterovirus Posteroanterior and lateral chest radiographs are (B) Herpes simplex virus type 1 negative. (C) Herpes simplex virus type 2 (D) West Nile virus Which ofthe following is the most appropriate management? (A) Isoniazid, daily for 6 months Item 81 (B) Isoniazid, daily for 9 months A72-year-old man is evaluated for a 2-day history of right (C) Isoniazid and rifampin, daily for 3 months facial drooping and burning pain on the right side of the tongue. He also reports a rash in the right ear. He reports (D) Isoniazid, rifampin, pyrazinamide, and ethambutol no other medical problems and takes no medications. On physical examination, vital signs are norrnal. Vesic- ular and some crusted lesions are seen on the right external Item 79 ear. Right facial palsy that includes the forehead is observed. A SO-year-old man is evaluated in the emergency depart- Tongue flndings are shown. ment for a chronic, nonpainful ulcer on the plantar aspect of his right foot that has recently begun to drain foul-smelling pus. Medical history is notable for type 2 diabetes mellitus and hypertension. Medications are metformin, canagli- flozin, and lisinopril. On physical examination, temperature is 37.9 "C (1OO.Z "F); other vital signs are normal. A 5- x 3-cm plantar ulcer draining pus is present on the right foot at the base of the third metatarsal with associated warmth, edema, and erythema. Right dorsalis pedis pulse is palpable. Bone cannot be visualized, and a metal probe cannot palpate bone. Laboratory studies show an erythrocyte sedimenta- tion rate of 100 mm/h and a leukocyte count of 12,500/pL (rz.s x Loe tL). A plain radiograph of the foot is normal. Which of the following is the most appropriate imaging test to perform next? (A) CT (B) Labeled leukocyte scan

Which of the following is the most appropriate next step in (u 3 days'duration. She lives in Minnesota. Medical history is ttt management? noncontributory, and her only medication is ibuprofen for (A) Intravenous penicillin and metronidazole headaches. (B) Intravenousvancomycin On physical examination, temperature is 3g "C (100.4 "F). (C) Lumbar puncture and culture of cerebrospinal fluid Other vital signs are norrnal. Other than a stiff neck and photophobia, the physical examination is normal. (D) Stereotactic needle aspiration of brain lesion Cerebrospinal fluid studies: Leukocyte count 276/1tL (ZZ0xLO6lL) with 45% neutrophils Item 78 Glucose 44 mg/dL (2.4 mmol/L) A 48-year-old woman is evaluated for an 18-mm indu- Protein 95 mg/dl (esO mgil) ration following tuberculin skin testing performed at her Gram stain Negative request following return from a medical mission in Peru Culture Pending 6 weeks ago. She reports possible exposure to tuberculo- A CT of the head with contrast is normal. sis. A fourth-generation HIV test and pregnancy test are negative. Which of the following is the most likely diagnosis? On physical examination, vital signs are normal, and the examination is unremarkable. (A) Enterovirus Posteroanterior and lateral chest radiographs are (B) Herpes simplex virus type 1 negative. (C) Herpes simplex virus type 2 (D) West Nile virus Which ofthe following is the most appropriate management? (A) Isoniazid, daily for 6 months Item 81 (B) Isoniazid, daily for 9 months A72-year-old man is evaluated for a 2-day history of right (C) Isoniazid and rifampin, daily for 3 months facial drooping and burning pain on the right side of the tongue. He also reports a rash in the right ear. He reports (D) Isoniazid, rifampin, pyrazinamide, and ethambutol no other medical problems and takes no medications. On physical examination, vital signs are norrnal. Vesic- ular and some crusted lesions are seen on the right external Item 79 ear. Right facial palsy that includes the forehead is observed. A SO-year-old man is evaluated in the emergency depart- Tongue flndings are shown. ment for a chronic, nonpainful ulcer on the plantar aspect of his right foot that has recently begun to drain foul-smelling pus. Medical history is notable for type 2 diabetes mellitus and hypertension. Medications are metformin, canagli- flozin, and lisinopril. On physical examination, temperature is 37.9 "C (1OO.Z "F); other vital signs are normal. A 5- x 3-cm plantar ulcer draining pus is present on the right foot at the base of the third metatarsal with associated warmth, edema, and erythema. Right dorsalis pedis pulse is palpable. Bone cannot be visualized, and a metal probe cannot palpate bone. Laboratory studies show an erythrocyte sedimenta- tion rate of 100 mm/h and a leukocyte count of 12,500/pL (rz.s x Loe tL). A plain radiograph of the foot is normal. Which of the following is the most appropriate imaging test to perform next? (A) CT (B) Labeled leukocyte scan 131

Self-Assessment Test t/t (D -lr a Which of the following is the most likely cause of this (D) Leptospirosis D UI patient's findings? (E) Parvovirus B-19 infection UI .D UI (A) Borrelia burgdorferi infection UI (B) Herpes simplex virus type 1 infection J (D .J t (C) Sarcoidosis (D) Varicella-zostervirus reactivation Item 84 A 48-year-old man is evaluated in the hospital 5 days after tr -l (D admission for increasing shortness of breath, productive UI r+ cough, pleuritic chest pain, fever, and chills. Medical history is notable for acute myelogenous leukemia, for which he was Item 82 receiving chemotherapy. Laboratory studies show a leuko- A 77-year-old woman is hospitalized for decompensated cyte count of 200/pL (O.Z x loe lL), with 75% neutrophils and heart failure. An indwelling urinary catheter is placed to 5% bands. Empiric therapy with cefepime and vancomycin monitor hourly urine output, and intravenous diuretics are was added to previously initiated prophylactic fluconazole. administered. Medical history is signiflcant for hyperten- On physical examination, temperature is 39.2 'C sion and untreated urinary incontinence. Her medications (toz.f'F), blood pressure is 125/60 mm Hg, pulse rate is are carvedilol, furosemide, and lisinopril. 128/min, and respiration rate is 26lmin. Crackles are heard On physical examination, blood pressure is 154/92 mm bilaterally on pulmonary auscultation. Hg, pulse rate is 100/min, and respiration rate is 18/min. Chest radiograph shows bilateral necrotizing broncho- Cardiopulmonary examination reveals bibasilar crackles pneumonia with multiple nodular and cavitary inflltrates. and an Sr. Bilateral lower extremity pitting edema is present Chest CT is shown. to the mid calf.

t/t (D -lr a Which of the following is the most likely cause of this (D) Leptospirosis D UI patient's findings? (E) Parvovirus B-19 infection UI .D UI (A) Borrelia burgdorferi infection UI (B) Herpes simplex virus type 1 infection J (D .J t (C) Sarcoidosis (D) Varicella-zostervirus reactivation Item 84 A 48-year-old man is evaluated in the hospital 5 days after tr -l (D admission for increasing shortness of breath, productive UI r+ cough, pleuritic chest pain, fever, and chills. Medical history is notable for acute myelogenous leukemia, for which he was Item 82 receiving chemotherapy. Laboratory studies show a leuko- A 77-year-old woman is hospitalized for decompensated cyte count of 200/pL (O.Z x loe lL), with 75% neutrophils and heart failure. An indwelling urinary catheter is placed to 5% bands. Empiric therapy with cefepime and vancomycin monitor hourly urine output, and intravenous diuretics are was added to previously initiated prophylactic fluconazole. administered. Medical history is signiflcant for hyperten- On physical examination, temperature is 39.2 'C sion and untreated urinary incontinence. Her medications (toz.f'F), blood pressure is 125/60 mm Hg, pulse rate is are carvedilol, furosemide, and lisinopril. 128/min, and respiration rate is 26lmin. Crackles are heard On physical examination, blood pressure is 154/92 mm bilaterally on pulmonary auscultation. Hg, pulse rate is 100/min, and respiration rate is 18/min. Chest radiograph shows bilateral necrotizing broncho- Cardiopulmonary examination reveals bibasilar crackles pneumonia with multiple nodular and cavitary inflltrates. and an Sr. Bilateral lower extremity pitting edema is present Chest CT is shown. to the mid calf. Which of the following is the most appropriate management to prevent urinary tract infection? (A) Administerprophylactictrimethoprim- sulfamethoxazole (B) Check urinalysis and urine culture on third day of catheterization (C) Remove indwelling urinary catheter (D) Replace indwelling urinary catheterwith an antiseptic- coated catheter

Which of the following is the most appropriate management to prevent urinary tract infection? (A) Administerprophylactictrimethoprim- sulfamethoxazole (B) Check urinalysis and urine culture on third day of catheterization (C) Remove indwelling urinary catheter (D) Replace indwelling urinary catheterwith an antiseptic- coated catheter Item 83 A 77-year-old woman is evaluated for fever, chills, and abdominal pain. Six weeks ago, she was hospitalized for gastrointestinal hemorrhage from a bleeding peptic ulcer. She received 2 units of packed red blood cells. She did well until l week ago when she noted increasing fatigue, shortness of breath with exertion, and low-grade fevers. She resides in an assisted living facility in Indiana and reports no history of out-of-state travel. Medical history is otherwise unremarkable, and she takes no medications. On physical examination, temperature is 3g.g .C (tOf.S "F); other vital signs are nornal. Scleral icterus is Serum galactomannan assay is positive. noted. The spleen tip is palpable. laboratory studies: Which of the following is the most likely cause of the patient's pneumonia? Haptoglobin 10 mg/dl (100 mg/L) Hematocrit 2s% (A) Aspergillus Leukocyte count 9800/pL (s.s x roetL) (B) Candida qlbicans Platelet count 133,000/pL (133 x 10e/L) (C) Crgptococcus neoformans Alanine aminotransferase 93U IL Aspartate aminotransferase (D) Histoplosma capsulatum 76U IL Alkaline phosphatase 10s u/L Bilirubin 3 mg/dl (sr pmol/L) Item 85 Which of the following is the most likely diagnosis? A 65-year-old man is evaluated for headaches, vomiting, EX (A) Babesiosis and fever of 5 days' duration. Medical history is notable for a ventriculoperitoneal shunt placed 2 years ago for hydro- (B) Cytomegalovirus infection cephalus following intracranial bleeding. He has hyperten- (C) Ehrlichiosis sion treated with chlorthalidone, losartan, and amlodipine.

Item 83 A 77-year-old woman is evaluated for fever, chills, and abdominal pain. Six weeks ago, she was hospitalized for gastrointestinal hemorrhage from a bleeding peptic ulcer. She received 2 units of packed red blood cells. She did well until l week ago when she noted increasing fatigue, shortness of breath with exertion, and low-grade fevers. She resides in an assisted living facility in Indiana and reports no history of out-of-state travel. Medical history is otherwise unremarkable, and she takes no medications. On physical examination, temperature is 3g.g .C (tOf.S "F); other vital signs are nornal. Scleral icterus is Serum galactomannan assay is positive. noted. The spleen tip is palpable. laboratory studies: Which of the following is the most likely cause of the patient's pneumonia? Haptoglobin 10 mg/dl (100 mg/L) Hematocrit 2s% (A) Aspergillus Leukocyte count 9800/pL (s.s x roetL) (B) Candida qlbicans Platelet count 133,000/pL (133 x 10e/L) (C) Crgptococcus neoformans Alanine aminotransferase 93U IL Aspartate aminotransferase (D) Histoplosma capsulatum 76U IL Alkaline phosphatase 10s u/L Bilirubin 3 mg/dl (sr pmol/L) Item 85 Which of the following is the most likely diagnosis? A 65-year-old man is evaluated for headaches, vomiting, EX (A) Babesiosis and fever of 5 days' duration. Medical history is notable for a ventriculoperitoneal shunt placed 2 years ago for hydro- (B) Cytomegalovirus infection cephalus following intracranial bleeding. He has hyperten- (C) Ehrlichiosis sion treated with chlorthalidone, losartan, and amlodipine. 132

Self-Assessment Test y UI m On physical examination, temperature is 38.6 .C (101.4 .F); Bone culture results show methicillin-susceptible Stoph- G' l- H blood pressure is 145i 98 mm Hg, pulse rate is 98/min, and res- ylococcus oureus susceptible to vancomycin, trimethoprim- +t ? coNT' piration rate is 18imin. Nuchal o, rigidity is present. The remain- sulfamethoxuole, doxycycline, and clindamycin. der of the neurologic examination is nonfocal. = UI l,I Which of the following is the most appropriate treatment? (u Cerebrospinal fluid studies: tt UI Leukocyte count fialp"L (Sg+ x 106IL),76"l,fleutrophils (A) Oral doxycycline rFI

y UI m On physical examination, temperature is 38.6 .C (101.4 .F); Bone culture results show methicillin-susceptible Stoph- G' l- H blood pressure is 145i 98 mm Hg, pulse rate is 98/min, and res- ylococcus oureus susceptible to vancomycin, trimethoprim- +t ? coNT' piration rate is 18imin. Nuchal o, rigidity is present. The remain- sulfamethoxuole, doxycycline, and clindamycin. der of the neurologic examination is nonfocal. = UI l,I Which of the following is the most appropriate treatment? (u Cerebrospinal fluid studies: tt UI Leukocyte count fialp"L (Sg+ x 106IL),76"l,fleutrophils (A) Oral doxycycline rFI Glucose 2SmgldL (1.6 mmol/L) (B) Parenteralceftaroline -Itt q, Protein 163 mg/dl (t6SO mg/L) (C) Parenteral piperacillin-tazobactam Lactate 0.69 mg/dl (O.S mmol/L) (normal: (D) Parenteralvancomycin 0.14-o.27 mgldl lt.s-z.q mmoliLl)

Glucose 2SmgldL (1.6 mmol/L) (B) Parenteralceftaroline -Itt q, Protein 163 mg/dl (t6SO mg/L) (C) Parenteral piperacillin-tazobactam Lactate 0.69 mg/dl (O.S mmol/L) (normal: (D) Parenteralvancomycin 0.14-o.27 mgldl lt.s-z.q mmoliLl) Cerebrospinal fluid cultures are pending. Item 88 Which of the following is the most appropriate empiric A 2S-year-old man is evaluated for ongoing, frequent diar- treatment? rhea, occurring approximately 10 times daily. He was diagnosed 2 weeks ago with HIV infection and frequent diarrhea, which (A) Intravenous ampicillin and ceftriaxone plus shunt was caused by Cryptospndium. Despite adherence to his med- removai ications, including antiretrovtals and an antimotility agent, his (B) Intravenous vancomycin and cefepime diarrhea continues. He has been able to maintain adequate oral (C) Intravenous vancomycin and cefepime plus shunt intake, but he reports associated nausea and abdominal cramp- removal ing. He plans to be a swimming instructor at a local municipal pool this summer. Medications are tenofovir alafenamide- (D) Intraventricularvancomycin plus meropenem emtricitabine, dolutegravir, trimethoprim-sulfamethoxazole, azithromycin, and loperamide. Item 86 On physical examination, temperature is 37.5 'C (99.5 'F), and other vital signs are normal. On abdominal A 36-year-old man is evaluated for fatigue, headache, myal- gia, arthralgia, and sore throat of 2 days' duration. He is also examination, bowel sounds are present, with mild pain to palpation without guarding. seeking HIV pre-exposure prophylaxis initiation. He has Two weeks ago, his CD4 cell count was 10/pL and HIV had multiple male and female sexual partners, with rare viral load was 250,000 copies/ml. condom use. His last sexual encounter was approximately 2 weeks ago. He takes no medications. On physical examination, vital signs are normal. Which of the following is the most appropriate treatment? Examination of the head and neck reveals anterior cervi- (A) Atovaquone cal and occipital lymphadenopathy; the remainder of the (B) Ciprofloxacin examination is unremarkable. Laboratory testing shows a negative fourth-generation (C) Nitazoxanide HIV -ll 2 antigen/antibody combination immunoassay and (D) Metronidazole negative serum rapid plasma reagin test.

Cerebrospinal fluid cultures are pending. Item 88 Which of the following is the most appropriate empiric A 2S-year-old man is evaluated for ongoing, frequent diar- treatment? rhea, occurring approximately 10 times daily. He was diagnosed 2 weeks ago with HIV infection and frequent diarrhea, which (A) Intravenous ampicillin and ceftriaxone plus shunt was caused by Cryptospndium. Despite adherence to his med- removai ications, including antiretrovtals and an antimotility agent, his (B) Intravenous vancomycin and cefepime diarrhea continues. He has been able to maintain adequate oral (C) Intravenous vancomycin and cefepime plus shunt intake, but he reports associated nausea and abdominal cramp- removal ing. He plans to be a swimming instructor at a local municipal pool this summer. Medications are tenofovir alafenamide- (D) Intraventricularvancomycin plus meropenem emtricitabine, dolutegravir, trimethoprim-sulfamethoxazole, azithromycin, and loperamide. Item 86 On physical examination, temperature is 37.5 'C (99.5 'F), and other vital signs are normal. On abdominal A 36-year-old man is evaluated for fatigue, headache, myal- gia, arthralgia, and sore throat of 2 days' duration. He is also examination, bowel sounds are present, with mild pain to palpation without guarding. seeking HIV pre-exposure prophylaxis initiation. He has Two weeks ago, his CD4 cell count was 10/pL and HIV had multiple male and female sexual partners, with rare viral load was 250,000 copies/ml. condom use. His last sexual encounter was approximately 2 weeks ago. He takes no medications. On physical examination, vital signs are normal. Which of the following is the most appropriate treatment? Examination of the head and neck reveals anterior cervi- (A) Atovaquone cal and occipital lymphadenopathy; the remainder of the (B) Ciprofloxacin examination is unremarkable. Laboratory testing shows a negative fourth-generation (C) Nitazoxanide HIV -ll 2 antigen/antibody combination immunoassay and (D) Metronidazole negative serum rapid plasma reagin test. Which ofthe following is the most appropriate management? (A) Check absolute CD4 cell count Item 89 A 36-year-old woman was hospitalized 3 days ago with tr fever of 4 days' duration. Medical history is significant for (B) Perform HIV-1RNA nucleic acid ampliflcation testing injection drug use. She takes no medications. (C) Start tenofovir-emtricitabine On initial physical examination, temperature was (D) Start tenofovir-emtricitabine plus dolutegravir 38.9'C (102.1 "F), blood pressure was 108/70 mm Hg, pulse rate was 100/min, and respiration rate was 2}lmin. Empiric vancomycin and ceftazidime treatment was Item 87 initiated. A7l-year -old man undergoes follow-up consultation regard- Today, the patient is improved. Temperature is 38.1 oC (tOO.s 'F); all other vital signs are norrnal. Blood cultures are ing a bone biopsy of the right flfth metatarsal head. The patient had a nonhealing ulcer on the plantar aspect of the positive for methicillin-resistant Staphylococcus aureus (van- right foot that developed 10 weeks ago. A plain radiograph comycin minimum inhibitory concentration l pgi mL). Vanco- showed evidence of osteomyelitis ofthe flfth metatarsal head, mycin trough level is 18 pglml. Ceftazidime is discontinued. and a biopsy of the involved bone was obtained. Medical his- Transthoracic echocardiogram shows a vegetation on the tricuspid valve. tory is notable for type 2 diabetes mellitus and hypertension. Medications are metformin, sitagliptin, and amlodipine. On physical examination, vital signs are normal. A Which ofthe followingis the mostappropriate management? 3- x 3-cm ulcer is located on the plantar aspect of the foot; (A) Add gentamicin and rifampin the ulcer base appears clean. The foot is warm with a palpa- (B) Area under the curve vancomycin-guided dosing ble dorsalis pedis pulse. Laboratory studies show a normal serum creatinine (C) Switch to daptomycin level. (D) Switch to telavancin

Which ofthe following is the most appropriate management? (A) Check absolute CD4 cell count Item 89 A 36-year-old woman was hospitalized 3 days ago with tr fever of 4 days' duration. Medical history is significant for (B) Perform HIV-1RNA nucleic acid ampliflcation testing injection drug use. She takes no medications. (C) Start tenofovir-emtricitabine On initial physical examination, temperature was (D) Start tenofovir-emtricitabine plus dolutegravir 38.9'C (102.1 "F), blood pressure was 108/70 mm Hg, pulse rate was 100/min, and respiration rate was 2}lmin. Empiric vancomycin and ceftazidime treatment was Item 87 initiated. A7l-year -old man undergoes follow-up consultation regard- Today, the patient is improved. Temperature is 38.1 oC (tOO.s 'F); all other vital signs are norrnal. Blood cultures are ing a bone biopsy of the right flfth metatarsal head. The patient had a nonhealing ulcer on the plantar aspect of the positive for methicillin-resistant Staphylococcus aureus (van- right foot that developed 10 weeks ago. A plain radiograph comycin minimum inhibitory concentration l pgi mL). Vanco- showed evidence of osteomyelitis ofthe flfth metatarsal head, mycin trough level is 18 pglml. Ceftazidime is discontinued. and a biopsy of the involved bone was obtained. Medical his- Transthoracic echocardiogram shows a vegetation on the tricuspid valve. tory is notable for type 2 diabetes mellitus and hypertension. Medications are metformin, sitagliptin, and amlodipine. On physical examination, vital signs are normal. A Which ofthe followingis the mostappropriate management? 3- x 3-cm ulcer is located on the plantar aspect of the foot; (A) Add gentamicin and rifampin the ulcer base appears clean. The foot is warm with a palpa- (B) Area under the curve vancomycin-guided dosing ble dorsalis pedis pulse. Laboratory studies show a normal serum creatinine (C) Switch to daptomycin level. (D) Switch to telavancin 133

Self-Assessment Test tt .D -D rh t Item 9O Laboratory studies show an erythrocyte sedimentation rate of 110 mm/h. UI A 64-year old woman is hospitalized for aZ-day history of UT A repeat plain radiograph shows evidence of soft tissue (D tn left-sided facial swelling, with associated pain and numb- I,l swelling with cortical destruction and accompanying peri- ness, and fever and chills. Medical history is signiflcant osteal reaction in the distal calcaneus. J (D for newly diagnosed, untreated, poorly controlled type 2 J diabetes mellitus. -i Which of the following is the most appropriate -l .D On physical examination, temperature is 39 oC ur (toz.z 'F), blood pressure is 150/88 mmm Hg, and pulse management? -t rate is 102/min. The clinical appearance of the patient is (A) Bone biopsy shown. (B) Ciprofloxacin (C) Linezolid (D) MRI with contrast (E) Three-phase nuclear bone scan

tt .D -D rh t Item 9O Laboratory studies show an erythrocyte sedimentation rate of 110 mm/h. UI A 64-year old woman is hospitalized for aZ-day history of UT A repeat plain radiograph shows evidence of soft tissue (D tn left-sided facial swelling, with associated pain and numb- I,l swelling with cortical destruction and accompanying peri- ness, and fever and chills. Medical history is signiflcant osteal reaction in the distal calcaneus. J (D for newly diagnosed, untreated, poorly controlled type 2 J diabetes mellitus. -i Which of the following is the most appropriate -l .D On physical examination, temperature is 39 oC ur (toz.z 'F), blood pressure is 150/88 mmm Hg, and pulse management? -t rate is 102/min. The clinical appearance of the patient is (A) Bone biopsy shown. (B) Ciprofloxacin (C) Linezolid (D) MRI with contrast (E) Three-phase nuclear bone scan Item 92 A 24-year-old woman is hospitalized for pelvic inflam- tr matory disease. Her symptoms include abdominal discomfort and nausea with poor oral intake. She is serually active with men but does not use condoms for all serual encounters. Her only medication is an oral contraceptive. On physical examination, temperatur:e is 39.1 'C (tOZ.g "F), blood pressure is 110i60 mm Hg, and pulse rate is 115rmin. Pelvic examination reveals mucopurulent dis- charge from the cervical os but no uterine or cervical motion tenderness, adnexal tenderness, or masses. Laboratory studies show a leukocyte count of 15,600ipl (tS.O x 1Oer'L). A serum pregnancy test is negative.

Item 92 A 24-year-old woman is hospitalized for pelvic inflam- tr matory disease. Her symptoms include abdominal discomfort and nausea with poor oral intake. She is serually active with men but does not use condoms for all serual encounters. Her only medication is an oral contraceptive. On physical examination, temperatur:e is 39.1 'C (tOZ.g "F), blood pressure is 110i60 mm Hg, and pulse rate is 115rmin. Pelvic examination reveals mucopurulent dis- charge from the cervical os but no uterine or cervical motion tenderness, adnexal tenderness, or masses. Laboratory studies show a leukocyte count of 15,600ipl (tS.O x 1Oer'L). A serum pregnancy test is negative. Which of the following is the most appropriate treatment? (A) Amoxicillin clavulanate and doxycycline (B) Cefbxitin and gentamicin (C) Ceftriaxone and azithromycin (D) Ceftriaxone and doxycycline Large, black, necrotic lesions are located on the upper palate. (E) Clindamycin and gentamicin

Which of the following is the most appropriate treatment? (A) Amoxicillin clavulanate and doxycycline (B) Cefbxitin and gentamicin (C) Ceftriaxone and azithromycin (D) Ceftriaxone and doxycycline Large, black, necrotic lesions are located on the upper palate. (E) Clindamycin and gentamicin Which of the following is the most likely diagnosis? Item 93 (A) Aspergillosis A 3l-year-old man is seen for follow-up discussion of HIV (B) Candidiasis testing. He reports a single extra marital encounter 6 weeks (C) Cryptococcus neoformansinfection ago without the use of a condom. He has never been diag- (D) Mucormycosis nosed with a sexually transmitted infection. He has been symptom free and takes no medications. The physical examination is unremarkable. Item 91 Subsequent testing shows a reactive fourth genera- A 42-year-old woman is evaluated for a 3-week history tion HIV-1/2 antigen/antibody combination assay, negative of increasing pain in the left heel. She sustained a punc- HIV-1 differentiation immunoassay, and negative HIV-1/2 ture wound from a nail 10 weeks ago. She was evaluated RNA nucleic acid ampliflcation test. promptly and given a tetanus immunization; a plain radio graph was normal. After initial improvement, the patient Which of the following is the most appropriate experienced progressively increasing pain over the injured management? area. (A) Check CD4 cell count On physical examination, vital signs are normal. Evi- dence of a healed wound is seen on the left heel. Mild edema (B) Provide HIV postexposure prophylaxis is noted with signiflcant tenderness on palpation but with (C) Repeat testing in l month out warmth, erythema, or drainage. (D) Reinforce safe sexual practice counseling

Which of the following is the most likely diagnosis? Item 93 (A) Aspergillosis A 3l-year-old man is seen for follow-up discussion of HIV (B) Candidiasis testing. He reports a single extra marital encounter 6 weeks (C) Cryptococcus neoformansinfection ago without the use of a condom. He has never been diag- (D) Mucormycosis nosed with a sexually transmitted infection. He has been symptom free and takes no medications. The physical examination is unremarkable. Item 91 Subsequent testing shows a reactive fourth genera- A 42-year-old woman is evaluated for a 3-week history tion HIV-1/2 antigen/antibody combination assay, negative of increasing pain in the left heel. She sustained a punc- HIV-1 differentiation immunoassay, and negative HIV-1/2 ture wound from a nail 10 weeks ago. She was evaluated RNA nucleic acid ampliflcation test. promptly and given a tetanus immunization; a plain radio graph was normal. After initial improvement, the patient Which of the following is the most appropriate experienced progressively increasing pain over the injured management? area. (A) Check CD4 cell count On physical examination, vital signs are normal. Evi- dence of a healed wound is seen on the left heel. Mild edema (B) Provide HIV postexposure prophylaxis is noted with signiflcant tenderness on palpation but with (C) Repeat testing in l month out warmth, erythema, or drainage. (D) Reinforce safe sexual practice counseling 134

Self-Assessment Test u ta Item 94 history is significant for type 2 diabetes and anaphylactic t-(u [22-year-oldwoman is evaluated inthe emergency depart- reaction to penicillin. She received the tetanus toxoid, reduced ? ment for a new-onset seizure and headache. She was born diphtheria toxoid, and acellular pertussis vaccine (Tdap) o in El Salvador and immigrated to the United States g years l year ago. Medications are metformin and empagliflozin. E t,t On physical examination, vital signs are normal. A few rtl ago. She is otherwise well and has no risk factors for HIV (I, tiny puncture wounds with minimal erythema are noted ta infection or other immunosuppressed condition. She takes ta no medications. over the dorsum of the left hand. a

u ta Item 94 history is significant for type 2 diabetes and anaphylactic t-(u [22-year-oldwoman is evaluated inthe emergency depart- reaction to penicillin. She received the tetanus toxoid, reduced ? ment for a new-onset seizure and headache. She was born diphtheria toxoid, and acellular pertussis vaccine (Tdap) o in El Salvador and immigrated to the United States g years l year ago. Medications are metformin and empagliflozin. E t,t On physical examination, vital signs are normal. A few rtl ago. She is otherwise well and has no risk factors for HIV (I, tiny puncture wounds with minimal erythema are noted ta infection or other immunosuppressed condition. She takes ta no medications. over the dorsum of the left hand. a On physical examination, vital signs are normal. Other Radiographs of the left hand reveal no evidence of a foreign body, gas, or bone involvement. The wound is = (1, vt than confusion, the examination is unremarkable. MRI of the brain is shown. irrigated and evaluated by a surgical hand expert, and no surgical intervention is required.

On physical examination, vital signs are normal. Other Radiographs of the left hand reveal no evidence of a foreign body, gas, or bone involvement. The wound is = (1, vt than confusion, the examination is unremarkable. MRI of the brain is shown. irrigated and evaluated by a surgical hand expert, and no surgical intervention is required. Which of the following is the most appropriate treatment? (A) Amoxicillin-clavulanate (B) Levofloxacin and metronidazole (C) Tetanusvaccination (D) Observation

Which of the following is the most appropriate treatment? (A) Amoxicillin-clavulanate (B) Levofloxacin and metronidazole (C) Tetanusvaccination (D) Observation Item 97 A 62-year-old man in the ICU is evaluated for fever and tr chills. He underwent a subtotal colectomy for stage III adenocarcinoma of the descending colon 8 days ago; 6 days ago, hospital-acquired pneumonia was diagnosed and piperacillin-tazobactam was initiated; the patient was moved to the ICU. He was improving but developed increas- ing fever and hypotension 2 days ago. Repeat blood cultures Which of the following is the most likely diagnosis? were obtained, a subclavian catheter was removed, and the (A) Neurocysticercosis tip was cultured. (B) Primary central nervous system lymphoma On physical examination today, temperature is 39.5 "C (tOS.t "F), blood pressure is 115160 mm Hg, pulse rate is (C) Pyogenic brain abscess 1o8imin, and respiration rate is 26lmin. Crackles are pres- (D) Toxoplasmosis ent at the lung bases bilaterally. The surgical wound is healing and nontender, and bowel sounds are present. The remainder of the examination is unremarkable. tr Item 95 A 40*year-old man presents to the emergency depart- Blood culture and catheter tip culture from 48 hours ago show budding yeast. ment with a 2-day history of diarrhea occurring six times daily that developed 1 week after completing a course of Which of the following is the most likely c:ruse of the amoxicillin-clavulanate for diverticulitis. Medical history patient's findings? is unremarkable, and he takes no medications. On physical examination, temperature is 38.3 "C (A) Blastomyces dermatitidis (tOO.q 'F); other vital signs are norrnal. Bowel sounds are (B) Candida albicans present; palpation elicits tenderness but no guarding. (C) Cryptococcus neoformans laboratory studies show a leukocyte count of 17,00OipL (D) Histoplasma capsulatum (tz x loelL). and serum creatinine level of 1.6 mgldL (141pmol/L). Stool testing for Clostridtoides dfficile is positive. Item 98 A 62-year-old man is evaluated for productive cough, pleu Which of the following is the most appropriate treatment? ritic chest pain, and night sweats of 2 months'duration. He (A) Intravenous metronidazole has had two courses of antibiotics for pneumonia without improvement. He lives in Arizona. Medical history is other- (B) Oral fidaxomicin wise unremarkable. (C) Oral vancomycin and rectal vancomycin On physical examination, temperature is 37.2 "C (D) Tapered and pulsed vancomycin (99 'F), blood pressure is Ll9l76 mm Hg, pulse rate is 94lmin, and respiration rate is 22lmin. Crackles are heard at the anterior right lower chest. Item 96 Chest radiograph shows a right middle lobe inflltrate A 4S-year-oldwoman is evaluated inthe emergencydepart- with associated hilar lymphadenopathy. ment for a bite on her hand sustained several hours earlier; HIV antigen/antibody combination immunoassay is the bite is from a toddler in her day care class. Medical negative. Sputum Gram stain and acid-fast bacilli stain are

Item 97 A 62-year-old man in the ICU is evaluated for fever and tr chills. He underwent a subtotal colectomy for stage III adenocarcinoma of the descending colon 8 days ago; 6 days ago, hospital-acquired pneumonia was diagnosed and piperacillin-tazobactam was initiated; the patient was moved to the ICU. He was improving but developed increas- ing fever and hypotension 2 days ago. Repeat blood cultures Which of the following is the most likely diagnosis? were obtained, a subclavian catheter was removed, and the (A) Neurocysticercosis tip was cultured. (B) Primary central nervous system lymphoma On physical examination today, temperature is 39.5 "C (tOS.t "F), blood pressure is 115160 mm Hg, pulse rate is (C) Pyogenic brain abscess 1o8imin, and respiration rate is 26lmin. Crackles are pres- (D) Toxoplasmosis ent at the lung bases bilaterally. The surgical wound is healing and nontender, and bowel sounds are present. The remainder of the examination is unremarkable. tr Item 95 A 40*year-old man presents to the emergency depart- Blood culture and catheter tip culture from 48 hours ago show budding yeast. ment with a 2-day history of diarrhea occurring six times daily that developed 1 week after completing a course of Which of the following is the most likely c:ruse of the amoxicillin-clavulanate for diverticulitis. Medical history patient's findings? is unremarkable, and he takes no medications. On physical examination, temperature is 38.3 "C (A) Blastomyces dermatitidis (tOO.q 'F); other vital signs are norrnal. Bowel sounds are (B) Candida albicans present; palpation elicits tenderness but no guarding. (C) Cryptococcus neoformans laboratory studies show a leukocyte count of 17,00OipL (D) Histoplasma capsulatum (tz x loelL). and serum creatinine level of 1.6 mgldL (141pmol/L). Stool testing for Clostridtoides dfficile is positive. Item 98 A 62-year-old man is evaluated for productive cough, pleu Which of the following is the most appropriate treatment? ritic chest pain, and night sweats of 2 months'duration. He (A) Intravenous metronidazole has had two courses of antibiotics for pneumonia without improvement. He lives in Arizona. Medical history is other- (B) Oral fidaxomicin wise unremarkable. (C) Oral vancomycin and rectal vancomycin On physical examination, temperature is 37.2 "C (D) Tapered and pulsed vancomycin (99 'F), blood pressure is Ll9l76 mm Hg, pulse rate is 94lmin, and respiration rate is 22lmin. Crackles are heard at the anterior right lower chest. Item 96 Chest radiograph shows a right middle lobe inflltrate A 4S-year-oldwoman is evaluated inthe emergencydepart- with associated hilar lymphadenopathy. ment for a bite on her hand sustained several hours earlier; HIV antigen/antibody combination immunoassay is the bite is from a toddler in her day care class. Medical negative. Sputum Gram stain and acid-fast bacilli stain are 135

Self-Assessment Test l/r (D +r negative. Blood cultures are negative. Sputum culture is 120/min, and respiration rate is 26lmin' Crackles are heard in both lung flelds. Abdominal examination reveals no hep- a t^ pending as is Coccidioidesurinary antigen. UI atosplenomegalY. .D UI UI Which of the following is the most likely diagnosis? I-aboratory studies: J Hemoglobin 10 g/dl (roo glt-) ID (A) Coccidioidomycosis Leukocyte count 3600/pL (g.o x 10e/L) J t (B) Klebsiellapneumonioepneumonia 109,000/pL (109 x 10e/L) { .D (C) Mgcobacterium tuberculosis infection Platelet count Alkaline phosphatase 312u lL UT 1-. (D) Sarcoidosis Alanine aminotransferase 51U/L Aspartate aminotransferase 58 U/L Serum and urinary Histoplosmo antigen are negative Item 99 Interferon-1 release assay is negative. A 43-year-old man is evaluated in the emergency department Chest radiograPh is shown. in early September for a 1-day history of Ieft facial weakness following 10 days of headache, stiff neck, and photophobia. He reports no sick contacts. He is a park ranger in Pennsylvania. His only medication is ibuprofen for headaches. On physical examination, temperature is 38.6 oC (rOr.S "F). Mental status is normal. A left facial cranial nerve (VII) palsy is noted. Cerebrospinal fluid studies show a leukocyte count of 95/pL (gS x tO6/L) with 90% lymphocytes, glucose level of 56 mg/dl (g.t mmol/L), and protein level of 76 mgldL (too mglL).

Serum and urinary Histoplosmo antigen are negative Item 99 Interferon-1 release assay is negative. A 43-year-old man is evaluated in the emergency department Chest radiograPh is shown. in early September for a 1-day history of Ieft facial weakness following 10 days of headache, stiff neck, and photophobia. He reports no sick contacts. He is a park ranger in Pennsylvania. His only medication is ibuprofen for headaches. On physical examination, temperature is 38.6 oC (rOr.S "F). Mental status is normal. A left facial cranial nerve (VII) palsy is noted. Cerebrospinal fluid studies show a leukocyte count of 95/pL (gS x tO6/L) with 90% lymphocytes, glucose level of 56 mg/dl (g.t mmol/L), and protein level of 76 mgldL (too mglL). Which of the following is the most likely diagnosis? (A) Enterovirus meningitis (B) Borreliaburgdorferimeningitis (C) Mycobocterium tuberculosis meningitis (D) West Nile virus meningitis Item 100 A 26-year-old woman is evaluated for acute cystitis of 2 days' duration. She is pregnant at 10 weeks' gestation. Medical history is signiflcant for postcoital lower urinary tract infections; her last infection was 6 months ago. Her only medication is a prenatal vitamin. Which of the following is the most likely diagnosis? On physical examination, vital signs and the examina- (A) Disseminatedhistoplasmosis tion are unremarkable. Dipstick urinalysis results show a pH of 7.1; positive (B) Disseminated tuberculosis leukocyte esterase, blood, and nitrites; and negative glu- (C) Streptococcus pneumonioebacteremia cose, protein, and ketones. (D) Subacute hypersensitivity pneumonia

Item 100 A 26-year-old woman is evaluated for acute cystitis of 2 days' duration. She is pregnant at 10 weeks' gestation. Medical history is signiflcant for postcoital lower urinary tract infections; her last infection was 6 months ago. Her only medication is a prenatal vitamin. Which of the following is the most likely diagnosis? On physical examination, vital signs and the examina- (A) Disseminatedhistoplasmosis tion are unremarkable. Dipstick urinalysis results show a pH of 7.1; positive (B) Disseminated tuberculosis leukocyte esterase, blood, and nitrites; and negative glu- (C) Streptococcus pneumonioebacteremia cose, protein, and ketones. (D) Subacute hypersensitivity pneumonia Which of the following is the most appropriate management? Item 1 O2 (A) Nitrofurantoin A 31-year-old man seeks advice regarding pre-exposure prophylaxis for HIV infection. He was treated for rectal (B) Trimethoprim-sulfamethoxazole gonorrhea 3 weeks ago and syphilis l year ago. He has not (C) Urine culture; cefpodoxime proxetil been sexually active since his gonorrhea diagnosis. He has (D) Urine culture; ciprofloxacin had receptive and insertive anal sex with multiple partners over the past year; condom use has been inconsistent. He takes no medications. Item 101 laboratory studies: A 38-year-old woman is hospitalized for fever, night sweats, Creatinine OJ mgldL (61.9 pmol/L) and a nonproductive cough of 6 weeks' duration. Medical Fourth generation HIV Negative history is signiflcant for Crohn disease. Her only medication antigen/ antibody combination is ustekinumab. immunoassay On physical examination, temperature is 39.6 "C Hepatitis B surface antigen Negative (tOe.S "F), blood pressure is 100/60 mm Hg, pulse rate is Hepatitis B surface antibody Positive

Which of the following is the most appropriate management? Item 1 O2 (A) Nitrofurantoin A 31-year-old man seeks advice regarding pre-exposure prophylaxis for HIV infection. He was treated for rectal (B) Trimethoprim-sulfamethoxazole gonorrhea 3 weeks ago and syphilis l year ago. He has not (C) Urine culture; cefpodoxime proxetil been sexually active since his gonorrhea diagnosis. He has (D) Urine culture; ciprofloxacin had receptive and insertive anal sex with multiple partners over the past year; condom use has been inconsistent. He takes no medications. Item 101 laboratory studies: A 38-year-old woman is hospitalized for fever, night sweats, Creatinine OJ mgldL (61.9 pmol/L) and a nonproductive cough of 6 weeks' duration. Medical Fourth generation HIV Negative history is signiflcant for Crohn disease. Her only medication antigen/ antibody combination is ustekinumab. immunoassay On physical examination, temperature is 39.6 "C Hepatitis B surface antigen Negative (tOe.S "F), blood pressure is 100/60 mm Hg, pulse rate is Hepatitis B surface antibody Positive 136

Self-Assessment Test vUt Repeat testing forgonorrhea, chlamydia, and syphitis is Which of the following is the most appropriate preventive o, F negative. He is counseled regarding consistent condom use measure? P E and the need for periodic screening for sexually transmitted (u infections. (A) Bismuthsubsalicylate E l,I (B) Ciprofloxacin ut (l, Daily treatment with which of the following is the most (C) Compact water fllter l,I l,I appropriate additional management? (D) Probiotics h a

vUt Repeat testing forgonorrhea, chlamydia, and syphitis is Which of the following is the most appropriate preventive o, F negative. He is counseled regarding consistent condom use measure? P E and the need for periodic screening for sexually transmitted (u infections. (A) Bismuthsubsalicylate E l,I (B) Ciprofloxacin ut (l, Daily treatment with which of the following is the most (C) Compact water fllter l,I l,I appropriate additional management? (D) Probiotics h a (A) Tenofovir (E) Rifaximin E tl (B) Tenofovir-emtricitabine (C) Tenofovir-emtricitabine and raltegravir (D) No additional treatment Item 106 A l7-year-old woman is evaluated in the emergency department in September for a 3-day history of headaches, tr low-grade fever, sore throat, cough, and stiff neck. She is tr Item 103 A 67-year-old man is hospitalized with new-onset blurred otherwise well and takes no medications. On physical examination, temperature is 37.9 'C (tOO.Z "F); the remainder of the vital signs are normal. The vision, trouble speaking, and dysphagia. He returned home 48 hours ago from a S-day Caribbean cruise. He felt well patient is alert, but photophobia is present on the ophthal- until the last day, when he developed nausea and loose moscopic examination. The neck is stiff. A rash is noted stools followed by constipation. Twenty other attendees over the face, thorax, and abdomen. The remainder of the have been hospitalized with similar symptoms. physical examination is unremarkable. On physical examination, vital signs are norrnal. He Representative flndings on the face are shown. exhibits dysphonia and dysarthria. The neckis supple. Lateral gaze nystagmus, abnormal ocular adduction, and sluggish dilated pupils are noted. Upper extremity motor weakness is present. Abdominal examination reveals distension and absent bowel sounds. Sensory examination, deep tendon reflexes, and the remainder of the examination are normal.

(A) Tenofovir (E) Rifaximin E tl (B) Tenofovir-emtricitabine (C) Tenofovir-emtricitabine and raltegravir (D) No additional treatment Item 106 A l7-year-old woman is evaluated in the emergency department in September for a 3-day history of headaches, tr low-grade fever, sore throat, cough, and stiff neck. She is tr Item 103 A 67-year-old man is hospitalized with new-onset blurred otherwise well and takes no medications. On physical examination, temperature is 37.9 'C (tOO.Z "F); the remainder of the vital signs are normal. The vision, trouble speaking, and dysphagia. He returned home 48 hours ago from a S-day Caribbean cruise. He felt well patient is alert, but photophobia is present on the ophthal- until the last day, when he developed nausea and loose moscopic examination. The neck is stiff. A rash is noted stools followed by constipation. Twenty other attendees over the face, thorax, and abdomen. The remainder of the have been hospitalized with similar symptoms. physical examination is unremarkable. On physical examination, vital signs are norrnal. He Representative flndings on the face are shown. exhibits dysphonia and dysarthria. The neckis supple. Lateral gaze nystagmus, abnormal ocular adduction, and sluggish dilated pupils are noted. Upper extremity motor weakness is present. Abdominal examination reveals distension and absent bowel sounds. Sensory examination, deep tendon reflexes, and the remainder of the examination are normal. Which of the following is the most likely diagnosis? (A) Acute flaccid myelitis (B) Botulism (C) Campylobocter-associated Guillain- Barrd syndrome (D) Paralytic shellfish poisoning

(A) Tenofovir (E) Rifaximin E tl (B) Tenofovir-emtricitabine (C) Tenofovir-emtricitabine and raltegravir (D) No additional treatment Item 106 A l7-year-old woman is evaluated in the emergency department in September for a 3-day history of headaches, tr low-grade fever, sore throat, cough, and stiff neck. She is tr Item 103 A 67-year-old man is hospitalized with new-onset blurred otherwise well and takes no medications. On physical examination, temperature is 37.9 'C (tOO.Z "F); the remainder of the vital signs are normal. The vision, trouble speaking, and dysphagia. He returned home 48 hours ago from a S-day Caribbean cruise. He felt well patient is alert, but photophobia is present on the ophthal- until the last day, when he developed nausea and loose moscopic examination. The neck is stiff. A rash is noted stools followed by constipation. Twenty other attendees over the face, thorax, and abdomen. The remainder of the have been hospitalized with similar symptoms. physical examination is unremarkable. On physical examination, vital signs are norrnal. He Representative flndings on the face are shown. exhibits dysphonia and dysarthria. The neckis supple. Lateral gaze nystagmus, abnormal ocular adduction, and sluggish dilated pupils are noted. Upper extremity motor weakness is present. Abdominal examination reveals distension and absent bowel sounds. Sensory examination, deep tendon reflexes, and the remainder of the examination are normal. Which of the following is the most likely diagnosis? (A) Acute flaccid myelitis (B) Botulism (C) Campylobocter-associated Guillain- Barrd syndrome (D) Paralytic shellfish poisoning Item 1O4 A 40-year-old man seeks treatment following a positive HIV Cerebrospinal fluid studies reveal a leukocyte count of test. Medical history is otherwise noncontributory, and he 35411tL (SS+ x 106/L), glucose level of 44 mg/dl (2.+ mmol/L), takes no medications. and protein level of 94 mgldL (940 mg/L). On physical examination, vital signs and the remainder of the examination are normal. Which of the following is the most likely cause of this HIV quantitative RNA is 500,000 copies/ml and CD4 patient's findings? cell count is 45lpl. (A) Enterovirus In addition to antiretroviral therapy initiation, which of the (B) Herpes simplex virus type 1 foltowing is the most appropriate prophylactic treatment? (C) Herpes simplex virus type 2 (A) Azithromycin (D) West Nile virus (B) Fluconazole (C) Trimethoprim-sulfamethoxazole (D) No additional management Item 1O7 A 76-year-old woman is being evaluated in follow-up for tr hospital-acquired pneumonia that was diagnosed 48 hours ago. Sputum Gram stain showed gram-positive cocci in clus- Item 105 ters. The patient had no risk factors for multidrug-resistant A 42-year-old woman seeks pretravel advice. She is travel- Pseudomonas or methicillin-resistant Staphylococcus ing to Guatemala City and will remain for 1week. She will aureus ; cefepime was started empirically. be visiting nearby villages during the flrst 4 days of her trip. On physical examination today, temperature is 38.4'C Medical history is notable for ulcerative colitis with occa- (tot.z oF), blood pressure is 122178 mm Hg, pulse rate is sional flares requiring glucocorticoid treatment. Her only 96lmin, and respiration rate is 20/min. Crackles are heard medication is mesalamine. at the left lung base.

Item 1O4 A 40-year-old man seeks treatment following a positive HIV Cerebrospinal fluid studies reveal a leukocyte count of test. Medical history is otherwise noncontributory, and he 35411tL (SS+ x 106/L), glucose level of 44 mg/dl (2.+ mmol/L), takes no medications. and protein level of 94 mgldL (940 mg/L). On physical examination, vital signs and the remainder of the examination are normal. Which of the following is the most likely cause of this HIV quantitative RNA is 500,000 copies/ml and CD4 patient's findings? cell count is 45lpl. (A) Enterovirus In addition to antiretroviral therapy initiation, which of the (B) Herpes simplex virus type 1 foltowing is the most appropriate prophylactic treatment? (C) Herpes simplex virus type 2 (A) Azithromycin (D) West Nile virus (B) Fluconazole (C) Trimethoprim-sulfamethoxazole (D) No additional management Item 1O7 A 76-year-old woman is being evaluated in follow-up for tr hospital-acquired pneumonia that was diagnosed 48 hours ago. Sputum Gram stain showed gram-positive cocci in clus- Item 105 ters. The patient had no risk factors for multidrug-resistant A 42-year-old woman seeks pretravel advice. She is travel- Pseudomonas or methicillin-resistant Staphylococcus ing to Guatemala City and will remain for 1week. She will aureus ; cefepime was started empirically. be visiting nearby villages during the flrst 4 days of her trip. On physical examination today, temperature is 38.4'C Medical history is notable for ulcerative colitis with occa- (tot.z oF), blood pressure is 122178 mm Hg, pulse rate is sional flares requiring glucocorticoid treatment. Her only 96lmin, and respiration rate is 20/min. Crackles are heard medication is mesalamine. at the left lung base. 137

Self-Assessment Test UI CD ..tr D (,I (n (D a tr CONI Sputum culture is now positive for methicillin-sensitive S. oureus. Blood cultures show no growth. and discharge are improving. Medical history includes no previous diagnosis of sexually transmitted infections. He takes no medications. UI tt Which of the following is the most appropriate treatrnent? Nucleic acid ampliflcation test results are positive for J chlamydia and negative for gonorrhea and herpes simplex (D (A) Continue cefepime virus. The syphilis enzyme immunoassay is positive, with .J 4 (B) Switch to cefazolin a negative rapid plasma reagin; a fluorescent treponemal -l (D (C) Switch to cephalexin antibody absorption test is positive. HIV serology is negative. * l,! (D) Switch to piperacillin-tazobactam Which of the following is the most appropriate treatment? Item 1OB (A) Amoxicillin A 24-year-old man undergoes consultation for test results following empiric therapy with ceftriaxone and (B) Benzathine penicillin azithromycin for sexually transmitted proctocolitis (C) Doxycycline and benzathine penicillin 3 days ago. His symptoms of mild rectal pain, tenesmus, (D) No treatment 138

Answers and Critiques tr Item 1 Answer: D Educational Objective: Treat central line-associated t(tY P0tItTs o Management of a central line-associated bloodstream bloodstream infection. infection often includes catheter removal with systemic The patient's peripherally inserted central catheter (plCC) antibiotic therapy targeted to the most likely organism should be removed, and penicillin shouki be switched to based on Gram stain result. intravenous cefepime (Option D). She has a gram-negative o Central venous catheter removal is always necessary in infection of the PICC. Appropriate management inclucles the presence of Stophylococcus aureus, Pseudomonas t (1, PICC removal with systemic antibiotic therapy targeted ae ruginos a, drug-resistant gram- negative bacilli, or - CT to the most likely organism. In patients r,vithout compli- Candida species bacteremia. a- F a- cations (e.g.. deep tissue infection or sepsis). it may be LT (J reasonable to delay the decision to remove the catheter .C' Bibliography E until the organism is identifled; catheter salvage lnay Guenezan J, Drugeon B. Marjanovic N, et al. Treatment of central line- att be considered in carefully selected cases using antibi- associated bloodstream infections [Editoriall. Crit Care. 2018122:303. |a L. IPM I D : SO++S gSOl doi 10. 11 86 /s 13054 ot9 -2249 -9 o, otic lock therapy (instillation of concentrated antibiotic :

tr Item 1 Answer: D Educational Objective: Treat central line-associated t(tY P0tItTs o Management of a central line-associated bloodstream bloodstream infection. infection often includes catheter removal with systemic The patient's peripherally inserted central catheter (plCC) antibiotic therapy targeted to the most likely organism should be removed, and penicillin shouki be switched to based on Gram stain result. intravenous cefepime (Option D). She has a gram-negative o Central venous catheter removal is always necessary in infection of the PICC. Appropriate management inclucles the presence of Stophylococcus aureus, Pseudomonas t (1, PICC removal with systemic antibiotic therapy targeted ae ruginos a, drug-resistant gram- negative bacilli, or - CT to the most likely organism. In patients r,vithout compli- Candida species bacteremia. a- F a- cations (e.g.. deep tissue infection or sepsis). it may be LT (J reasonable to delay the decision to remove the catheter .C' Bibliography E until the organism is identifled; catheter salvage lnay Guenezan J, Drugeon B. Marjanovic N, et al. Treatment of central line- att be considered in carefully selected cases using antibi- associated bloodstream infections [Editoriall. Crit Care. 2018122:303. |a L. IPM I D : SO++S gSOl doi 10. 11 86 /s 13054 ot9 -2249 -9 o, otic lock therapy (instillation of concentrated antibiotic : 3 U} into the catheter lumen) when drug-susceptible Esche- E richia coli, Klebsiello species, Enterobacter species, and Item 2 Answer: B coagulase negative staphylococci are present. Catheter Educationa I O bjective : Treat pharyngeal gonorrhea. removal is always necessary in the presence of Staphylo- coccus eLtreLts, Pseudomonas aeruginoso, drug-resistant The patient has pharyngeal gonorrhea and should be treated gram negative bacilli. or Candido species. The common with ceftriaxone (Option B). He had unprotected sexual con gram negative organisms causing central line associated tact with a new partner; a detailed sexual history is neces- bloodstream infections (CLABSIs) ir-rclude E. coli and sary so that all potential sites of exposure can be screened Kle bsie lla speci es : cefepi me or pi pertrcillin -tazobactam is for sexually transmitted infections (STIs). Infection may be appropriate as empiric coverage pending organism iden- asymptomatic. For screening and diagnosis, nucleic acid tification and susceptibility testing results. These antibi- amplification testing (NAAT) is preferred. Testing for coin- otics also provide coverage fbr the concomitant group B fections, speciflcally Chlamydia trachomatis, should also be Streptococcus osteomyelitis, which still reqr"rires treat- performed at the same time. Based on this patient's history ment (4 0 weeks total). Blood cultures should be obtained NAAT for gonorrhea and chlamydia from a flrst catch urine after catheter removal and initiation of appropriate anti sample and a pharyngeal swab would be indicated. The rec- biotic therapy to document clearance of the organism. ommended treatment for pharyngeal or genital gonorrhea is Treatment shouid be targeted n,hen susceptibility results a single dose of intramuscular ceftriaxone. are available; duration is 7 to 14 days for uncomplicated The CDC reports no reliable alternative treatments infections. for pharyngeal gonorrhea. For persons with a history of Vancomycin is freqr-rently the pref'erred ar-rtibiotic fbr B-lactam allergz, a thorough assessment of the reaction is CLABSI caused by gram-positive organisms. For situa- recommended. For persons with a documented severe reac- tions in which the vancomycin inhibitory concentration tion to ceftriaxone, consultation with an infectious disease is greater than 2 prgrml, daptornycin (Option A) would specialist for an alternate treatment is recommended. Cefix- be a reasonable alternertive. This patient has a gram- ime (Option A) or cefuroxime (Option E) cannot be recom- negative infection, so neither vancomycin nor daptomycin mended for this patient. is indicated. The CDC recommends ceftriaxone monotherapy for For critically ill patients, multidrug resistant gram- treatment of uncomplicated gonorrhea of the cervix, ure- negative organisms should be considered, and empiric car- thra, rectum, and pharynx because N. gonorrhoeoe remains bapenem therapy (e.g., meropenerl, imipenem) (Option B) susceptible to ceftriaxone, azithromycin resistance is n-ray be more appropriate (provides activity against extended- increasing, and thoughtful antimicrobial prescribing sup- spectrum p-lactamase-producing gram negative organ- ports limiting azithromycin use (Option C). isms). This patient does not have an indication for treatment The preferred treatment for uncomplicated gonorrhea with a carbapenem. is ceftriaxone monotherapy. The addition of doxycycline Penicillin (Option C) does not provide the necess:rry (Option D) is indicated only if chlamydia infection has not gram negative coverage and should be switched to a more been excluded; the preferred treatment includes a single appropriate antibiotic that also covers group B Streptococcus dose of ceftriaxone plus doxycycline for 7 days. During preg- such as cef-epime. nancy, a single oral dose of azithromycin should replace

3 U} into the catheter lumen) when drug-susceptible Esche- E richia coli, Klebsiello species, Enterobacter species, and Item 2 Answer: B coagulase negative staphylococci are present. Catheter Educationa I O bjective : Treat pharyngeal gonorrhea. removal is always necessary in the presence of Staphylo- coccus eLtreLts, Pseudomonas aeruginoso, drug-resistant The patient has pharyngeal gonorrhea and should be treated gram negative bacilli. or Candido species. The common with ceftriaxone (Option B). He had unprotected sexual con gram negative organisms causing central line associated tact with a new partner; a detailed sexual history is neces- bloodstream infections (CLABSIs) ir-rclude E. coli and sary so that all potential sites of exposure can be screened Kle bsie lla speci es : cefepi me or pi pertrcillin -tazobactam is for sexually transmitted infections (STIs). Infection may be appropriate as empiric coverage pending organism iden- asymptomatic. For screening and diagnosis, nucleic acid tification and susceptibility testing results. These antibi- amplification testing (NAAT) is preferred. Testing for coin- otics also provide coverage fbr the concomitant group B fections, speciflcally Chlamydia trachomatis, should also be Streptococcus osteomyelitis, which still reqr"rires treat- performed at the same time. Based on this patient's history ment (4 0 weeks total). Blood cultures should be obtained NAAT for gonorrhea and chlamydia from a flrst catch urine after catheter removal and initiation of appropriate anti sample and a pharyngeal swab would be indicated. The rec- biotic therapy to document clearance of the organism. ommended treatment for pharyngeal or genital gonorrhea is Treatment shouid be targeted n,hen susceptibility results a single dose of intramuscular ceftriaxone. are available; duration is 7 to 14 days for uncomplicated The CDC reports no reliable alternative treatments infections. for pharyngeal gonorrhea. For persons with a history of Vancomycin is freqr-rently the pref'erred ar-rtibiotic fbr B-lactam allergz, a thorough assessment of the reaction is CLABSI caused by gram-positive organisms. For situa- recommended. For persons with a documented severe reac- tions in which the vancomycin inhibitory concentration tion to ceftriaxone, consultation with an infectious disease is greater than 2 prgrml, daptornycin (Option A) would specialist for an alternate treatment is recommended. Cefix- be a reasonable alternertive. This patient has a gram- ime (Option A) or cefuroxime (Option E) cannot be recom- negative infection, so neither vancomycin nor daptomycin mended for this patient. is indicated. The CDC recommends ceftriaxone monotherapy for For critically ill patients, multidrug resistant gram- treatment of uncomplicated gonorrhea of the cervix, ure- negative organisms should be considered, and empiric car- thra, rectum, and pharynx because N. gonorrhoeoe remains bapenem therapy (e.g., meropenerl, imipenem) (Option B) susceptible to ceftriaxone, azithromycin resistance is n-ray be more appropriate (provides activity against extended- increasing, and thoughtful antimicrobial prescribing sup- spectrum p-lactamase-producing gram negative organ- ports limiting azithromycin use (Option C). isms). This patient does not have an indication for treatment The preferred treatment for uncomplicated gonorrhea with a carbapenem. is ceftriaxone monotherapy. The addition of doxycycline Penicillin (Option C) does not provide the necess:rry (Option D) is indicated only if chlamydia infection has not gram negative coverage and should be switched to a more been excluded; the preferred treatment includes a single appropriate antibiotic that also covers group B Streptococcus dose of ceftriaxone plus doxycycline for 7 days. During preg- such as cef-epime. nancy, a single oral dose of azithromycin should replace 139

Answers and Critiques doxycycline. This patient's NAAT was negative for C' tracho- virus is associated with inhalation of aerosolized rodent matis, making combination therapy unne ce ssary' excrement or urine rather than bird exposure' Rhodococcus equi is a gram-positive coccobacil- t([Y P0lt{Ts Ius associated with exposure to horses (Option E)' It is . A detailed sexual history is important to obtain so that an unusual cause of CAB occurring primarily in immuno- all potential sites of exposure can be screened for sex- compromised hosts and in patients with HIV infection in ually transmitted infections. particular. Rhodococcus pneumonia typically presents as a . The recommended treatment for pharyngeal or pulmonary nodule or cavitary lesion. genital gonorrhea is a single dose of intramuscular KEY POIilI ceftriaxone. o Chlamadia psittaci presents indistinguishably from other causes of interstitial pneumonia such as Bibliography Chlamy dophila p neumoniae or My coplosma species, D St Cyr S, Barbee L, Workowski KA, et al. Update to CDC's treatment guide- - UI lines for gonococcal infection, 2020. MMWR Morb Mortal Wkly Rep' so a history of bird exposure is helpful in correctly 2O2O :69 :1911 1916. IPMID : SS\SZZSO] doi:10.15585/mmrn'r'mm6950a6 identifiiing the organism. (D = - UI q, Bibliography )EL Item 3 Answer: B Shaw KA, Szablewski CM, Kellner S, et al. Psittacosis outbreak among workers a-l Ed u cati o na I O bjective : Diagnose Ch lom ydia psittaci at chicken slaughter plants, Virginia and Georgia, USA, 2018. Emerg Infect -t pneumonia. Dis. 2019;25:2t43-2l4s. [PMID: STOZSSSS] doi:10.3201/eid2511.190703

doxycycline. This patient's NAAT was negative for C' tracho- virus is associated with inhalation of aerosolized rodent matis, making combination therapy unne ce ssary' excrement or urine rather than bird exposure' Rhodococcus equi is a gram-positive coccobacil- t([Y P0lt{Ts Ius associated with exposure to horses (Option E)' It is . A detailed sexual history is important to obtain so that an unusual cause of CAB occurring primarily in immuno- all potential sites of exposure can be screened for sex- compromised hosts and in patients with HIV infection in ually transmitted infections. particular. Rhodococcus pneumonia typically presents as a . The recommended treatment for pharyngeal or pulmonary nodule or cavitary lesion. genital gonorrhea is a single dose of intramuscular KEY POIilI ceftriaxone. o Chlamadia psittaci presents indistinguishably from other causes of interstitial pneumonia such as Bibliography Chlamy dophila p neumoniae or My coplosma species, D St Cyr S, Barbee L, Workowski KA, et al. Update to CDC's treatment guide- - UI lines for gonococcal infection, 2020. MMWR Morb Mortal Wkly Rep' so a history of bird exposure is helpful in correctly 2O2O :69 :1911 1916. IPMID : SS\SZZSO] doi:10.15585/mmrn'r'mm6950a6 identifiiing the organism. (D = - UI q, Bibliography )EL Item 3 Answer: B Shaw KA, Szablewski CM, Kellner S, et al. Psittacosis outbreak among workers a-l Ed u cati o na I O bjective : Diagnose Ch lom ydia psittaci at chicken slaughter plants, Virginia and Georgia, USA, 2018. Emerg Infect -t pneumonia. Dis. 2019;25:2t43-2l4s. [PMID: STOZSSSS] doi:10.3201/eid2511.190703 It IO

doxycycline. This patient's NAAT was negative for C' tracho- virus is associated with inhalation of aerosolized rodent matis, making combination therapy unne ce ssary' excrement or urine rather than bird exposure' Rhodococcus equi is a gram-positive coccobacil- t([Y P0lt{Ts Ius associated with exposure to horses (Option E)' It is . A detailed sexual history is important to obtain so that an unusual cause of CAB occurring primarily in immuno- all potential sites of exposure can be screened for sex- compromised hosts and in patients with HIV infection in ually transmitted infections. particular. Rhodococcus pneumonia typically presents as a . The recommended treatment for pharyngeal or pulmonary nodule or cavitary lesion. genital gonorrhea is a single dose of intramuscular KEY POIilI ceftriaxone. o Chlamadia psittaci presents indistinguishably from other causes of interstitial pneumonia such as Bibliography Chlamy dophila p neumoniae or My coplosma species, D St Cyr S, Barbee L, Workowski KA, et al. Update to CDC's treatment guide- - UI lines for gonococcal infection, 2020. MMWR Morb Mortal Wkly Rep' so a history of bird exposure is helpful in correctly 2O2O :69 :1911 1916. IPMID : SS\SZZSO] doi:10.15585/mmrn'r'mm6950a6 identifiiing the organism. (D = - UI q, Bibliography )EL Item 3 Answer: B Shaw KA, Szablewski CM, Kellner S, et al. Psittacosis outbreak among workers a-l Ed u cati o na I O bjective : Diagnose Ch lom ydia psittaci at chicken slaughter plants, Virginia and Georgia, USA, 2018. Emerg Infect -t pneumonia. Dis. 2019;25:2t43-2l4s. [PMID: STOZSSSS] doi:10.3201/eid2511.190703 It IO - F .D Chlamydia psittaci is the most likely cause of community- UI acquired pneumonia (CAP) in this patient, considering his history of bird exposure and clinical presentation (Option B). C. psittaci is the cause of psittacosis ("parrot fever"). A Item 4 Answer: B Ed ucati o na I O bjective : Treat ventilator-associated tr pneumonia in a patient with risk firctors for antimicrobial- meta-analysis determined psittacosis accounts for 1'lo of all resistant pathogens. CAP infections. Human infections are caused by inhalation of droppings (urine or feces) from birds, but because the The most appropriate treatment for this patient is ceftazi- organism can remain infectious in the environment for dime, ciprofloxacin, and vancomycin (Option B). Empiric months, a history of avian exposure is not always present. therapy for ventilator-associated pneumonia (VAP) should Clinically, C. psittaci presents indistinguishably from other include coverage for Staphylococcus aurelts, Pseudomonas causes of interstitial pneumonia such as Chlamydophila aeruginosa, and other gram-negative bacilli. Empiric cov- pneumoniae or Mycoplasmo species; therefore, a history erage for antibiotic-resistant organisms is recommended for of bird exposure is helpful in suggesting the diagnosis. patients who have risk factors for antibiotic resistance (pre- Laboratory conflrmation of infection is challenging because vious intravenous antibiotics within 90 days; septic shock the organism is fastidious, and culture is not routinely at the time of VAP diagnosis; acute respiratory distress syn- available outside of research settings. Serologic testing drome preceding VAP; 5 or more hospitalized days before may provide retrospective diagnosis, but antibodies are VAP: or undergoing dialysis before VAP onset). This patient variably present during acute illness. Polymerase chain has risk factors for methicillin-resistanl S. aureus (MRSA) and reaction of respiratory specimens is highly sensitive and antibiotic-resistant Pseudomonos, so two antipseudomonal speciflc but not widely available. When the diagnosis is agents from diflerent antibiotic classes (such as a B-lactam suspected, empiric treatment options include doxycycline, and a fluoroquinolone) are indicated. Vancomycin would be macrolides, or fluoroquinolones; treatment should be con- included in the empiric regimen to cover MRSA. Microbiologic tinued for 10 to 14 days. results should be reviewed as soon as they are available, and Avian influenza strains have been responsible for world- antibiotic therapy appropriately adjusted to the narrowest wide pandemics, with the H7N9 strain flrst identifled in 2013 spectrum possible. in China (Option A). Human infection with this strain is Ceftazidime and vancomycin (Option A) provides only associated with poultry exposure; however, infections have a single antipseudomonal agent; however, two antipseudo not been identifled outside of Asia. monal agents are needed fbr this patient's empiric regimen. Coxiella burnetii, the cause of Q fever, causes pneu- Ertapenem (Option C) is a carbapenem with good monia through inhalation of infectious aerosols (Option C). gram negative activify, but it has limited to no activity High bacterial levels are present in amniotic fluid, and assist- against P aeruginoso. It also has no activity against MRSA. ing in the birthing of farm animals such as cattle, sheep, and Piperacillin-tazobactam (Option D) provides empiric goats is associated with infection. Birds are uncommon res- coverage for methicillin-sensitive S. aureus, P. aeruginosa, ervoirs for C. burnetii. and other gram-negative bacilli and would be appropriate Hanta virus causes a severe cardiopulmonary syndrome for a patient without risk factors for antibiotic-resistant bac characterizedby acute respiratory distress syndrome, hemo- teria; however, the regimen lacks necessary dual antipseu- concentration, and thrombocytopenia (Option D). Hanta domonal coverage needed for this patient.

- F .D Chlamydia psittaci is the most likely cause of community- UI acquired pneumonia (CAP) in this patient, considering his history of bird exposure and clinical presentation (Option B). C. psittaci is the cause of psittacosis ("parrot fever"). A Item 4 Answer: B Ed ucati o na I O bjective : Treat ventilator-associated tr pneumonia in a patient with risk firctors for antimicrobial- meta-analysis determined psittacosis accounts for 1'lo of all resistant pathogens. CAP infections. Human infections are caused by inhalation of droppings (urine or feces) from birds, but because the The most appropriate treatment for this patient is ceftazi- organism can remain infectious in the environment for dime, ciprofloxacin, and vancomycin (Option B). Empiric months, a history of avian exposure is not always present. therapy for ventilator-associated pneumonia (VAP) should Clinically, C. psittaci presents indistinguishably from other include coverage for Staphylococcus aurelts, Pseudomonas causes of interstitial pneumonia such as Chlamydophila aeruginosa, and other gram-negative bacilli. Empiric cov- pneumoniae or Mycoplasmo species; therefore, a history erage for antibiotic-resistant organisms is recommended for of bird exposure is helpful in suggesting the diagnosis. patients who have risk factors for antibiotic resistance (pre- Laboratory conflrmation of infection is challenging because vious intravenous antibiotics within 90 days; septic shock the organism is fastidious, and culture is not routinely at the time of VAP diagnosis; acute respiratory distress syn- available outside of research settings. Serologic testing drome preceding VAP; 5 or more hospitalized days before may provide retrospective diagnosis, but antibodies are VAP: or undergoing dialysis before VAP onset). This patient variably present during acute illness. Polymerase chain has risk factors for methicillin-resistanl S. aureus (MRSA) and reaction of respiratory specimens is highly sensitive and antibiotic-resistant Pseudomonos, so two antipseudomonal speciflc but not widely available. When the diagnosis is agents from diflerent antibiotic classes (such as a B-lactam suspected, empiric treatment options include doxycycline, and a fluoroquinolone) are indicated. Vancomycin would be macrolides, or fluoroquinolones; treatment should be con- included in the empiric regimen to cover MRSA. Microbiologic tinued for 10 to 14 days. results should be reviewed as soon as they are available, and Avian influenza strains have been responsible for world- antibiotic therapy appropriately adjusted to the narrowest wide pandemics, with the H7N9 strain flrst identifled in 2013 spectrum possible. in China (Option A). Human infection with this strain is Ceftazidime and vancomycin (Option A) provides only associated with poultry exposure; however, infections have a single antipseudomonal agent; however, two antipseudo not been identifled outside of Asia. monal agents are needed fbr this patient's empiric regimen. Coxiella burnetii, the cause of Q fever, causes pneu- Ertapenem (Option C) is a carbapenem with good monia through inhalation of infectious aerosols (Option C). gram negative activify, but it has limited to no activity High bacterial levels are present in amniotic fluid, and assist- against P aeruginoso. It also has no activity against MRSA. ing in the birthing of farm animals such as cattle, sheep, and Piperacillin-tazobactam (Option D) provides empiric goats is associated with infection. Birds are uncommon res- coverage for methicillin-sensitive S. aureus, P. aeruginosa, ervoirs for C. burnetii. and other gram-negative bacilli and would be appropriate Hanta virus causes a severe cardiopulmonary syndrome for a patient without risk factors for antibiotic-resistant bac characterizedby acute respiratory distress syndrome, hemo- teria; however, the regimen lacks necessary dual antipseu- concentration, and thrombocytopenia (Option D). Hanta domonal coverage needed for this patient. 140

Answers and Criti ques KEY POITTS partner is also unlikely to provide beneflt considering the o Empiric therapy for ventilator_associated pneumonia patient's sustained virologic suppression (Option B, C). should include coverage for Staphylococcus aureus, I(EY POI I{T Pseudomonos aeruginosa, and other gram_negative o The risk of HIV transmission is essentially zero in bacilli. patients who have a sustained, undetectable viral load o Empiric treatment for antibiotic_resistant organisms is for at least 6 months (Undetectable = Untransmittable), recommended for patients with ventilator_associated so monogamous, serodifferent partners do not require pneumonia who have risk factors for antibiotic further HIV prevention measures. resistance, including intravenous antibiotics within 90 days and more than S days in the hospital before Bibliography diagnosis. Rodger AJ, Cambiano V Bruun T, et al; PARTNER Study Group. Sexual activ_ ity without condoms and risk of HIV transmission in serodifferent cou_ ples when the HIV positive partner is using suppressive antiretroviral UI Bibliography o therapy. JAMA. 2016 3 t6 (2) J7 t-tlt. ; J- Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator,associated pneumonia: 2016 clinical .g F practice guidelines by the Infectious Diseases Society of America and L the U American Thoracic Society. Clin Infect Dis. 2Ot6;6j(S):e61_elll. [pMtO, 27 4185771 doi:10.1093 /cid/ciw3S3 Item 6 Answer: D ?t L Educational Objective: Manage a patient with fit rrt L posttreatment Lyme disease syndrome. q,

KEY POITTS partner is also unlikely to provide beneflt considering the o Empiric therapy for ventilator_associated pneumonia patient's sustained virologic suppression (Option B, C). should include coverage for Staphylococcus aureus, I(EY POI I{T Pseudomonos aeruginosa, and other gram_negative o The risk of HIV transmission is essentially zero in bacilli. patients who have a sustained, undetectable viral load o Empiric treatment for antibiotic_resistant organisms is for at least 6 months (Undetectable = Untransmittable), recommended for patients with ventilator_associated so monogamous, serodifferent partners do not require pneumonia who have risk factors for antibiotic further HIV prevention measures. resistance, including intravenous antibiotics within 90 days and more than S days in the hospital before Bibliography diagnosis. Rodger AJ, Cambiano V Bruun T, et al; PARTNER Study Group. Sexual activ_ ity without condoms and risk of HIV transmission in serodifferent cou_ ples when the HIV positive partner is using suppressive antiretroviral UI Bibliography o therapy. JAMA. 2016 3 t6 (2) J7 t-tlt. ; J- Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator,associated pneumonia: 2016 clinical .g F practice guidelines by the Infectious Diseases Society of America and L the U American Thoracic Society. Clin Infect Dis. 2Ot6;6j(S):e61_elll. [pMtO, 27 4185771 doi:10.1093 /cid/ciw3S3 Item 6 Answer: D ?t L Educational Objective: Manage a patient with fit rrt L posttreatment Lyme disease syndrome. q, Item 5 This patient has posttreatment Lyme disease syndrome l,t = Answer: D E (PTLDS), and providing reassurance, supportive care, and Educational Objective: Manage HIV transmission risk serial evaluation are the mainstays of management (Option D). between serodiscordant partners. Nonspeciflc constitutional symptoms that linger for months No additional prevention strategz is necessary (Option D). after Lyme disease treatment are common. Among patients Persons with HIV infection who have at least 6 months of with solitary or multiple erythema migrans (EM) skin lesions, sustained viral suppression have eflectively no risk of sexually posttreatment symptoms occur in up to 2Oo/o at 2 months, 16% transmitting HIV to HlV-negative partners. A large multi- at 6 months, and 6"/u at12 months. PTLDS is deflned as symp- center, observational study of HIV serodiscordant couples toms that are sufficiently severe as to limit the previous level (including same-sex and heterosexual couples) showed no of functioning persisting 6 months or more after antibiotic transmissions of HIV during condomless sex from eflectively therapy. No evidence supports ongoing infection as a cause treated HlV-positive to HlV-negative partners. Several other of these symptoms, and studies evaluating prolonged use of studies have similarly shown that HlV-positive persons with antibiotics in this population have not shown beneflt. Recom- sustained viral suppression do not transmit HIV to their sex- mendations for patients experiencing symptoms after being ual partners. This is described as "Undetectable = Untrans- diagnosed with Lyme disease are to evaluate for alternative mittable" (U = U), which was endorsed by the CDC in 2017. causes and provide therapy to lessen symptoms. Patients can The most important factor is that the HlV-positive partner is be reassured that symptoms typically subside with time. consistently taking antiretroviral therapy (ART) and achieves EM is diagnostic of early localized Lyme disease in viral suppression, maintaining an undetectable viral load for endemic areas (or Southern Tick-Associated Rash illness at least 6 months. U = U has been particularly endorsed to outside of these regions). This patient was appropriately minimize stigma around HIV, and it is encouraged that phy- treated with doxycycline based on the clinical flnding of sicians involved in the care of persons with HIV share this EM. Alternative options include amoxicillin or cefuroxime important update with their patients. axetil, which are also effective in preventing dissemination Condom use is unlikely to provide further HIV preven of infection and subsequent development of extracutaneous tion in this committed, monogamous relationship consid- manifestations. Retreatment has no role in the management ering the HIV-positive partner's sustained viral suppression of patients with prolonged symptoms or PTLDS (Option A). (Option A). Lyme disease encephalopathy is a subset of PTLDS in This patient's risk for transmitting HIV to his partner is which neurocognitive symptoms such as fatigue, confusion, effectively zero. HIV pre-exposure prophylaxis (PrEP) is an impaired memory or poor concentration predominate. No effective tool for HIV prevention and is often recommended evidence supports parenchymal infection as a cause of these for HlV-negative partners in serodiscordant relationships vague symptoms, and lumbar puncture is not indicated in to prevent HIV acquisition from the HlV-positive partner. the absence of objective flndings of neurologic dysfunction However, PrEP is most beneflcial when the HIV positive (Option B). partner is not taking ART or does not have sustained viral Lyme serologies would likely be positive in this patient suppression. Recommending daily or on-demand PrEP but would not be helpful in conflrming the clinical diagnosis ("2-l-1" strate$/ of two pills on the day of planned sexual of Lyme disease or determining the cause of her ongoing exposure and one pill on the subsequent 2 days) for the symptoms (Option C).

Item 5 This patient has posttreatment Lyme disease syndrome l,t = Answer: D E (PTLDS), and providing reassurance, supportive care, and Educational Objective: Manage HIV transmission risk serial evaluation are the mainstays of management (Option D). between serodiscordant partners. Nonspeciflc constitutional symptoms that linger for months No additional prevention strategz is necessary (Option D). after Lyme disease treatment are common. Among patients Persons with HIV infection who have at least 6 months of with solitary or multiple erythema migrans (EM) skin lesions, sustained viral suppression have eflectively no risk of sexually posttreatment symptoms occur in up to 2Oo/o at 2 months, 16% transmitting HIV to HlV-negative partners. A large multi- at 6 months, and 6"/u at12 months. PTLDS is deflned as symp- center, observational study of HIV serodiscordant couples toms that are sufficiently severe as to limit the previous level (including same-sex and heterosexual couples) showed no of functioning persisting 6 months or more after antibiotic transmissions of HIV during condomless sex from eflectively therapy. No evidence supports ongoing infection as a cause treated HlV-positive to HlV-negative partners. Several other of these symptoms, and studies evaluating prolonged use of studies have similarly shown that HlV-positive persons with antibiotics in this population have not shown beneflt. Recom- sustained viral suppression do not transmit HIV to their sex- mendations for patients experiencing symptoms after being ual partners. This is described as "Undetectable = Untrans- diagnosed with Lyme disease are to evaluate for alternative mittable" (U = U), which was endorsed by the CDC in 2017. causes and provide therapy to lessen symptoms. Patients can The most important factor is that the HlV-positive partner is be reassured that symptoms typically subside with time. consistently taking antiretroviral therapy (ART) and achieves EM is diagnostic of early localized Lyme disease in viral suppression, maintaining an undetectable viral load for endemic areas (or Southern Tick-Associated Rash illness at least 6 months. U = U has been particularly endorsed to outside of these regions). This patient was appropriately minimize stigma around HIV, and it is encouraged that phy- treated with doxycycline based on the clinical flnding of sicians involved in the care of persons with HIV share this EM. Alternative options include amoxicillin or cefuroxime important update with their patients. axetil, which are also effective in preventing dissemination Condom use is unlikely to provide further HIV preven of infection and subsequent development of extracutaneous tion in this committed, monogamous relationship consid- manifestations. Retreatment has no role in the management ering the HIV-positive partner's sustained viral suppression of patients with prolonged symptoms or PTLDS (Option A). (Option A). Lyme disease encephalopathy is a subset of PTLDS in This patient's risk for transmitting HIV to his partner is which neurocognitive symptoms such as fatigue, confusion, effectively zero. HIV pre-exposure prophylaxis (PrEP) is an impaired memory or poor concentration predominate. No effective tool for HIV prevention and is often recommended evidence supports parenchymal infection as a cause of these for HlV-negative partners in serodiscordant relationships vague symptoms, and lumbar puncture is not indicated in to prevent HIV acquisition from the HlV-positive partner. the absence of objective flndings of neurologic dysfunction However, PrEP is most beneflcial when the HIV positive (Option B). partner is not taking ART or does not have sustained viral Lyme serologies would likely be positive in this patient suppression. Recommending daily or on-demand PrEP but would not be helpful in conflrming the clinical diagnosis ("2-l-1" strate$/ of two pills on the day of planned sexual of Lyme disease or determining the cause of her ongoing exposure and one pill on the subsequent 2 days) for the symptoms (Option C). 141

Answers and Critiques Ceftriaxone plus azithromycin would be an appropriate f,EY POITTS alternatir,'e if this patient dicl not have a history of immediate o Patients may experience nonspecific constitutional (Option B)' hypersensitivity reaction to p-lactanr irntibiotics symptoms that linger for months after Lyme disease Residence ir-r a skilled nursing facility is not an inde- treatment, and reassurance, supportive care, and serial pendent risk factor fbr Pseudonlonas pneumonia' so an evaluation should be provided in the management of antipseudomonal agent sttch as meropenem is not indicated posttreatment Lyme disease syndrome' for empiric theraPY (OPtion D). . No evidence supports ongoing infection as a cause of Morifloxacin monotherapy would be an appropriate posttreatment Lyme disease syndrome, and prolonged choice, but the addition of empiric clindamycin increases use of antibiotics in this population has not shown the risk of Clostrid ioides difficile colitis r't'ith minirnal thera- peutic beneflt (OPtion E). benefit. t( EY PO l llTS D Bibliography o Patients with community-acquired pneumonia requir- J IA Aucott JN. Posttreatment Lyme disease syndrome. Infect Dis Clin North Am E 2015;29(2):30 g -323. Iptr,ltO, zssggzzol doi:10.1016/j.idc'2015'02'012 ing hospitalization can be treated with the standard tD r: inpatient regimens regardless of a documented aspira- vt o, tion event. Item 7 Answer: C rJ EL n rl tr Educational Objective: Treat communit5r-acquired o Antibiotic coverage for anaerobic organisms can be considered in patients with pneumonia characterized * pneumonia following aspiration. by the presence of empyema, lung abscess, or postob- 4l s This patient has aspiration pneumonia r,l'ithout complicatiotrs structive pneumonia. .D t (such as lung abscess or empyema), so standard therapy fbr community acquired pneumonia (CAP) n,ith a respiratory Bibliography quinolone (levofloxacin) is appropriate (Option C). Aspira- Mandell LA, Niederman MS. Aspiration pneumonia. N Engl J Med. 2019; tion pneunronia is estirnated to accottnt for 5'7, to 15'){, of 380:651 -663. [PMIO, 30763196] doi:10.1056/NElMral714562

Ceftriaxone plus azithromycin would be an appropriate f,EY POITTS alternatir,'e if this patient dicl not have a history of immediate o Patients may experience nonspecific constitutional (Option B)' hypersensitivity reaction to p-lactanr irntibiotics symptoms that linger for months after Lyme disease Residence ir-r a skilled nursing facility is not an inde- treatment, and reassurance, supportive care, and serial pendent risk factor fbr Pseudonlonas pneumonia' so an evaluation should be provided in the management of antipseudomonal agent sttch as meropenem is not indicated posttreatment Lyme disease syndrome' for empiric theraPY (OPtion D). . No evidence supports ongoing infection as a cause of Morifloxacin monotherapy would be an appropriate posttreatment Lyme disease syndrome, and prolonged choice, but the addition of empiric clindamycin increases use of antibiotics in this population has not shown the risk of Clostrid ioides difficile colitis r't'ith minirnal thera- peutic beneflt (OPtion E). benefit. t( EY PO l llTS D Bibliography o Patients with community-acquired pneumonia requir- J IA Aucott JN. Posttreatment Lyme disease syndrome. Infect Dis Clin North Am E 2015;29(2):30 g -323. Iptr,ltO, zssggzzol doi:10.1016/j.idc'2015'02'012 ing hospitalization can be treated with the standard tD r: inpatient regimens regardless of a documented aspira- vt o, tion event. Item 7 Answer: C rJ EL n rl tr Educational Objective: Treat communit5r-acquired o Antibiotic coverage for anaerobic organisms can be considered in patients with pneumonia characterized * pneumonia following aspiration. by the presence of empyema, lung abscess, or postob- 4l s This patient has aspiration pneumonia r,l'ithout complicatiotrs structive pneumonia. .D t (such as lung abscess or empyema), so standard therapy fbr community acquired pneumonia (CAP) n,ith a respiratory Bibliography quinolone (levofloxacin) is appropriate (Option C). Aspira- Mandell LA, Niederman MS. Aspiration pneumonia. N Engl J Med. 2019; tion pneunronia is estirnated to accottnt for 5'7, to 15'){, of 380:651 -663. [PMIO, 30763196] doi:10.1056/NElMral714562 CAP occurrences. This patient has multiple risk factors for aspiration, including residence in a nursit-tg home, neuro logic in-rpairment. v'omiting, and the presence of a percu- taneous gastrostomy feeding tube. Suctionir-rg of tube f'eed Item 8 Answer: C Educational Objective: Treat hospital-acquired tr methicill in - sen sitive Staphy lococc us o,ureus bacteremi a. material conflrms aspiration of gastric contents into the lungs, although a witnessed or confirmed aspiration event is rare. The most appropriate nlanagement is switching to cefazolin Among patients with gastrostomy tubes, chronic low-grade (Option C). Following the discovery of an infected periph- aspiration of oropharyngeal contents is the most common eral venons catheter site in a febrile patient, appropriate risk factor fbr aspiration pneumonia. which remains the actions include removing the line, obtaining blood cul- leadir-rg cause of death in this population. Nern, insights into tures. and starting empiric vancomycin therapy to cover the pathophysiologz of CAP l-rave identi{ied that aspiration the possibility of hospital-acquired methicillin-resistant is not restricted to patients with classic risk factors (e.g., Staphylococcus aureus (MRSA) infection. When the blood dysphagia, neurologic dysfunction, or gastroesophageal cultures identify methicillin sensitive S. oureus (MSSA), reflux disease). Silent aspiration is recognized as a common antibiotic treatment should be de escalated. Bacteremia phenomenon, and most CAP infections result from caused by MSSA should be treated intravenously with a microaspiration of bacteria colonizing the respiratory tract. penicillinase-resistant semisynthetic penicillin (such Aspiration pneumonia occurs along a continuum and rep- as oxacillin) or flrst generatior-r cephalosporin (such as resents macroaspiration of a larger quantity of material cefazolin) at maximal doses. Vancomycin (Option B)should in patients who are unable to protect their airway. Recent be avoided in patients with MSSA who are not allergic to studies have also found that the microbiolory of aspira- B-lactam antibiotics; vancomycin is associated with higher tion pneumonia is similar to other causes of CAP, r.t,ith rates of relapse and microbiologic failure in the treatment oropharyngeai flora such as StreptococcLts pneumoniae, of MSSA bacteremia. Haemopltilus influenzae. and gram-negative organisms Combination antimicrobial therapy (such as vancomy- predominating. Anaerobes are rarely identified in contem- cin and rifampin) (Option A) for the treatment of S. ourcus porary studies of aspiration pneumonia; therefbre. dedi bacteremia has not been shown to improve clinical out- cated anaerobic coverage is not necessary althor"rgh it could comes and should not be used. Furthermore, this patient's be considered in the presence of empyema. lung abscess, or antibiotic regimen should be de-escalated to ir B-lactam postobstructive pneumonia. antibiotic based on blood culture results. Aztreonam plus metronidazole does not cover pneu- All patients with S. oureus bacteremia should undergo mococcus or other gram-positive organisms; therefore, echocardiography. Transthoracic echocardiography (TTE) is this combination would be suboptintal for empiric therapy usually performed first; if a vegetation is identified on TTE, (Option A). transesophageal echocardiography (TEE) (Option D) rnay

CAP occurrences. This patient has multiple risk factors for aspiration, including residence in a nursit-tg home, neuro logic in-rpairment. v'omiting, and the presence of a percu- taneous gastrostomy feeding tube. Suctionir-rg of tube f'eed Item 8 Answer: C Educational Objective: Treat hospital-acquired tr methicill in - sen sitive Staphy lococc us o,ureus bacteremi a. material conflrms aspiration of gastric contents into the lungs, although a witnessed or confirmed aspiration event is rare. The most appropriate nlanagement is switching to cefazolin Among patients with gastrostomy tubes, chronic low-grade (Option C). Following the discovery of an infected periph- aspiration of oropharyngeal contents is the most common eral venons catheter site in a febrile patient, appropriate risk factor fbr aspiration pneumonia. which remains the actions include removing the line, obtaining blood cul- leadir-rg cause of death in this population. Nern, insights into tures. and starting empiric vancomycin therapy to cover the pathophysiologz of CAP l-rave identi{ied that aspiration the possibility of hospital-acquired methicillin-resistant is not restricted to patients with classic risk factors (e.g., Staphylococcus aureus (MRSA) infection. When the blood dysphagia, neurologic dysfunction, or gastroesophageal cultures identify methicillin sensitive S. oureus (MSSA), reflux disease). Silent aspiration is recognized as a common antibiotic treatment should be de escalated. Bacteremia phenomenon, and most CAP infections result from caused by MSSA should be treated intravenously with a microaspiration of bacteria colonizing the respiratory tract. penicillinase-resistant semisynthetic penicillin (such Aspiration pneumonia occurs along a continuum and rep- as oxacillin) or flrst generatior-r cephalosporin (such as resents macroaspiration of a larger quantity of material cefazolin) at maximal doses. Vancomycin (Option B)should in patients who are unable to protect their airway. Recent be avoided in patients with MSSA who are not allergic to studies have also found that the microbiolory of aspira- B-lactam antibiotics; vancomycin is associated with higher tion pneumonia is similar to other causes of CAP, r.t,ith rates of relapse and microbiologic failure in the treatment oropharyngeai flora such as StreptococcLts pneumoniae, of MSSA bacteremia. Haemopltilus influenzae. and gram-negative organisms Combination antimicrobial therapy (such as vancomy- predominating. Anaerobes are rarely identified in contem- cin and rifampin) (Option A) for the treatment of S. ourcus porary studies of aspiration pneumonia; therefbre. dedi bacteremia has not been shown to improve clinical out- cated anaerobic coverage is not necessary althor"rgh it could comes and should not be used. Furthermore, this patient's be considered in the presence of empyema. lung abscess, or antibiotic regimen should be de-escalated to ir B-lactam postobstructive pneumonia. antibiotic based on blood culture results. Aztreonam plus metronidazole does not cover pneu- All patients with S. oureus bacteremia should undergo mococcus or other gram-positive organisms; therefore, echocardiography. Transthoracic echocardiography (TTE) is this combination would be suboptintal for empiric therapy usually performed first; if a vegetation is identified on TTE, (Option A). transesophageal echocardiography (TEE) (Option D) rnay 142

Answers and Critiques tr CONI not be needed. However. if no vegetation is seen on TTE. 'l'EE should be considered. TEE may not be necessary after a negative TTlr in some patients with unconrplicated S. nureus sustained fevers while in the hospital rather than a biphasic illness and did not grow resistant organisms on repeat cul_ tures, making this diagnosis unlikely. bacteremia. including in health care acquired bacterernia. Synergistic therapy with gentamicin is not indicated for when repeat blood cultures witl-rin 96 hours of' the first MRSA (Option B). It would increase the risk of kidney dys_ positive culture are negative; if the patient is not unclergoing function without the benefit of lung penetration. hernodialysis; when no perntanent intracardiac prosthetic Bronchoscopy is a reasonable diagnostic approach for devices are preserlt (e.g.. mechanical cardiac valves); w,hen pathogen identiflcation in patients with CAp unresponsive no signs of endocarditis or secondary fbci of infbction are to empiric therapy (Option C). The causative organism of present; if f'ever resolves within 72 l-rours of the first positive this patient's infection is already known; therefore, bron- blood culture; and when the focus of intbction is promptly choscopy would be unlikely to provide useful information. removed. 'lhis patient may meet the criteria fbr ur-rcompli- cated S, riureus bacterernia after repeat blclotl culture results rEV POIl{T ta are known. If'the bktod cultures are persister-rtly positive. . Ongoing fever in patients with community-acquired (l, J further ir-rvestigation is warranted to deterntine the source. pneumonia suggests either infection with an organism a- ET P andTEE should be pursued. not adequately covered by empiric antibiotics or inad- .I L equate source control. rJ -E' I(EY POITTS ]- . All patients with Stophylococcus aureusbacteremia Bibliography ru t L should undergo echocardiography. Pinnola A, Kuo YH, Sciarretta JD, et al. Bacteriolory and comorbidities in C' o Transesophageal echocardiography may not be neces- patients requiring surgical management of empyema. Am Surg. 201g; ul 84:599-603. [PMID: ZSt tZOts) = E sary after a negative transthoracic echocardiography in some patients with uncomplicated Staphylococcus Item 10 Answer: D oureus bacteremia at low risk for endocarditis.

tr CONI not be needed. However. if no vegetation is seen on TTE. 'l'EE should be considered. TEE may not be necessary after a negative TTlr in some patients with unconrplicated S. nureus sustained fevers while in the hospital rather than a biphasic illness and did not grow resistant organisms on repeat cul_ tures, making this diagnosis unlikely. bacteremia. including in health care acquired bacterernia. Synergistic therapy with gentamicin is not indicated for when repeat blood cultures witl-rin 96 hours of' the first MRSA (Option B). It would increase the risk of kidney dys_ positive culture are negative; if the patient is not unclergoing function without the benefit of lung penetration. hernodialysis; when no perntanent intracardiac prosthetic Bronchoscopy is a reasonable diagnostic approach for devices are preserlt (e.g.. mechanical cardiac valves); w,hen pathogen identiflcation in patients with CAp unresponsive no signs of endocarditis or secondary fbci of infbction are to empiric therapy (Option C). The causative organism of present; if f'ever resolves within 72 l-rours of the first positive this patient's infection is already known; therefore, bron- blood culture; and when the focus of intbction is promptly choscopy would be unlikely to provide useful information. removed. 'lhis patient may meet the criteria fbr ur-rcompli- cated S, riureus bacterernia after repeat blclotl culture results rEV POIl{T ta are known. If'the bktod cultures are persister-rtly positive. . Ongoing fever in patients with community-acquired (l, J further ir-rvestigation is warranted to deterntine the source. pneumonia suggests either infection with an organism a- ET P andTEE should be pursued. not adequately covered by empiric antibiotics or inad- .I L equate source control. rJ -E' I(EY POITTS ]- . All patients with Stophylococcus aureusbacteremia Bibliography ru t L should undergo echocardiography. Pinnola A, Kuo YH, Sciarretta JD, et al. Bacteriolory and comorbidities in C' o Transesophageal echocardiography may not be neces- patients requiring surgical management of empyema. Am Surg. 201g; ul 84:599-603. [PMID: ZSt tZOts) = E sary after a negative transthoracic echocardiography in some patients with uncomplicated Staphylococcus Item 10 Answer: D oureus bacteremia at low risk for endocarditis. Bibliography Educational Objective: Treat a flrst episode of nonsevere tr Clo stridioides dfficile i nfection. Barton I Moir S, Rehmani H, et al. Low rates of endocarditis in healthcare- associated Staphylococcus aureus bacteremia suggest that echocardiog 'lhis patient has an initial episode of'nonsevere Closfridioides raphy might not always be required. Eur i Clin Microbiol lnfect Dis. 2016; 35 :49-55. [P]tllO' 264901391 diJJicile inf'ection (CDI). 'uvhich should be treated nith oral vancornycin therapy (Option D). Risk factors fbr infbction ir-rclude exposure to antibiotic and chemotherapeutic agents. Item 9 Answer: D olcler age, presence of inf lartrnatory bowel disease. gastroin testir-ral surgery and (possibly) gastric acid suppressior-r with Ed u catio na I O bj ective : Manage community-acquired protort pump inhibitors. Antibiotic stewardship is paramount pneumonia failing to respond to antibiotic therapy. in reducing incidence of inlbction. and hand washing with This patient has an empyema, and thoracentesis and drain- soap and water is the gold standard fbr infbction colrtrol; age should be performed (Option D). Ongoing fevers alcol-rol based gels clo not elinrinate spores. Disease se\€r suggest either infection with an organism not adequately ity (rronsevere, severe. ancl lirh-nir-rant) and initial or lecur- covered by empiric antibiotics or inadequate source control. rcnt presetrtation guide treatment selection. Nonse'rrere CDI In this patient, CT imaging reveals an empyema, recognized is clefined by a leukocyte cor-urt of less than l5,000rprl as enhancement of the pleura around the fluid creating a (15 x l0ei L) and a serunr creatinine level of less than L5 ntg/dl- lenticular-shaped opacity. This patient's blood cultures grew (133 prrnol/L).'lhe 2017 Inf'ectious Diseases Society o1'America methicillin-resistant Staphylococcus aureus (MRSA), and and Society fbr Healthclre Epiderniolory of America clinical vancomycin was initiated. Vancomycin with a minimum practice guideline fbr CDI recorrmends either oral 'u'lrnccxny inhibitory concentration of (0.5 pg/ml (indicating suscep- cin or oral fidaxomicin firr treatment of an initial episode of tibility) is appropriate therapy for parenchymal infection but nonsevere or se\,ere disease. lf'these agents are unavailable or would not penetrate the empyema. Empyema occurs in up to intolerable. oral metronidazole (Option C) can be used ftrr an 10'/, of patients with community-acquired pneumonia (CAP) initial episode of nonsevere clisease. and is most commonly caused by streptococcal organisms or I.ecal microbiota transplantation (Option A) has been anaerobes. However, S. aureus is increasingly recognized as recommended as a treatment approach fbr patients with a cause of necrotizing pneumonia and associated empyema, nrultiple relapses of'CDL 'll-re rationale is that exogenous particularly in patients with risk factors for MRSA such as teces will restore the normal color-ric nricrobiota. L,ecal recent antibiotic use, hospitalization, influenza-like illness, rnicrobiota transplantation is not recortmended fbr ar-r ini- end-stage kidney disease, and injection drug use. tial episode of nonsevere CDl. Adding empiric cefepime could be considered in a lntravenous vancornycir-r (Option B) is rtot recom- patient who develops secondary hospital acquired pneu- nrencled fbr treatn-rent of'CDl becar-rse it is not excreted intcr monia as the cause of fever (Option A). This patient had the large intestine.

Bibliography Educational Objective: Treat a flrst episode of nonsevere tr Clo stridioides dfficile i nfection. Barton I Moir S, Rehmani H, et al. Low rates of endocarditis in healthcare- associated Staphylococcus aureus bacteremia suggest that echocardiog 'lhis patient has an initial episode of'nonsevere Closfridioides raphy might not always be required. Eur i Clin Microbiol lnfect Dis. 2016; 35 :49-55. [P]tllO' 264901391 diJJicile inf'ection (CDI). 'uvhich should be treated nith oral vancornycin therapy (Option D). Risk factors fbr infbction ir-rclude exposure to antibiotic and chemotherapeutic agents. Item 9 Answer: D olcler age, presence of inf lartrnatory bowel disease. gastroin testir-ral surgery and (possibly) gastric acid suppressior-r with Ed u catio na I O bj ective : Manage community-acquired protort pump inhibitors. Antibiotic stewardship is paramount pneumonia failing to respond to antibiotic therapy. in reducing incidence of inlbction. and hand washing with This patient has an empyema, and thoracentesis and drain- soap and water is the gold standard fbr infbction colrtrol; age should be performed (Option D). Ongoing fevers alcol-rol based gels clo not elinrinate spores. Disease se\€r suggest either infection with an organism not adequately ity (rronsevere, severe. ancl lirh-nir-rant) and initial or lecur- covered by empiric antibiotics or inadequate source control. rcnt presetrtation guide treatment selection. Nonse'rrere CDI In this patient, CT imaging reveals an empyema, recognized is clefined by a leukocyte cor-urt of less than l5,000rprl as enhancement of the pleura around the fluid creating a (15 x l0ei L) and a serunr creatinine level of less than L5 ntg/dl- lenticular-shaped opacity. This patient's blood cultures grew (133 prrnol/L).'lhe 2017 Inf'ectious Diseases Society o1'America methicillin-resistant Staphylococcus aureus (MRSA), and and Society fbr Healthclre Epiderniolory of America clinical vancomycin was initiated. Vancomycin with a minimum practice guideline fbr CDI recorrmends either oral 'u'lrnccxny inhibitory concentration of (0.5 pg/ml (indicating suscep- cin or oral fidaxomicin firr treatment of an initial episode of tibility) is appropriate therapy for parenchymal infection but nonsevere or se\,ere disease. lf'these agents are unavailable or would not penetrate the empyema. Empyema occurs in up to intolerable. oral metronidazole (Option C) can be used ftrr an 10'/, of patients with community-acquired pneumonia (CAP) initial episode of nonsevere clisease. and is most commonly caused by streptococcal organisms or I.ecal microbiota transplantation (Option A) has been anaerobes. However, S. aureus is increasingly recognized as recommended as a treatment approach fbr patients with a cause of necrotizing pneumonia and associated empyema, nrultiple relapses of'CDL 'll-re rationale is that exogenous particularly in patients with risk factors for MRSA such as teces will restore the normal color-ric nricrobiota. L,ecal recent antibiotic use, hospitalization, influenza-like illness, rnicrobiota transplantation is not recortmended fbr ar-r ini- end-stage kidney disease, and injection drug use. tial episode of nonsevere CDl. Adding empiric cefepime could be considered in a lntravenous vancornycir-r (Option B) is rtot recom- patient who develops secondary hospital acquired pneu- nrencled fbr treatn-rent of'CDl becar-rse it is not excreted intcr monia as the cause of fever (Option A). This patient had the large intestine. 143

Answers and Critiques l+tl Oral vancomycin (by mouth or nasogastric tube) and such as Mycoplasma or Chlamydophila are possible causes bl 1,-,1.rvenous metronidazole (Option E) is recommended fbr of severe CAP. Starting ceftriaxone monotherapy would not CONT ful*inant CDI. Fulminant CDI is associated with hypoten- include coverage against any of these fastidious organisms sion, shock, ileus, or megacolon. If an ileus is present, rectal and would not be appropriate (Option C). instillation of vancomycin should be considered. Patients I(EY POI ilT with fulminant disease warrant surgical evaluation. o In patients with severe community-acquired pneu- rEY POIHTS monia who have stabilized and have negative culture . Treatment for initial nonsevere or severe Clostridioides results for resistant organisms, antimicrobial therapy dfficile infection is either oral vancomycin or oral can be de-escalated to a standard regimen for nonse- fidaxomicin. vere disease. . Oral metronidazole may be used for an initial episode of nonsevere Clostridioides dfficile infection if vanco Bibliography J Viasus D, Vecino-Moreno M, De La Hoz JM, et al. Antibiotic stewardship UI mycin and fidaxomicin are unavailable or intolerable. in community-acquired pneumonia. Expert Rev Anti Infect Ther. { (D = 2017;15:351-359. [PMIO' zeoOzstgl doi:10.1080/14787210.2017. UI r274232 Bibtiography o, J McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for EL Clostridium difficile infection in adults and children: 2017 update by the n rI Infectious Diseases Society of America (IDSA) and Society for Healthcare * Epidemiologz of America (SHEA). Clin Infect Dis. 2018;66987-994. Item 12 Answer: A ll? IPMIO, 29562266) doi:10.1093 /cidl ciyl49 Ed ucationa I Objective: Treat secondary syphilis. (D UI A single dose of benzathine penicillin is the most appropri-

l+tl Oral vancomycin (by mouth or nasogastric tube) and such as Mycoplasma or Chlamydophila are possible causes bl 1,-,1.rvenous metronidazole (Option E) is recommended fbr of severe CAP. Starting ceftriaxone monotherapy would not CONT ful*inant CDI. Fulminant CDI is associated with hypoten- include coverage against any of these fastidious organisms sion, shock, ileus, or megacolon. If an ileus is present, rectal and would not be appropriate (Option C). instillation of vancomycin should be considered. Patients I(EY POI ilT with fulminant disease warrant surgical evaluation. o In patients with severe community-acquired pneu- rEY POIHTS monia who have stabilized and have negative culture . Treatment for initial nonsevere or severe Clostridioides results for resistant organisms, antimicrobial therapy dfficile infection is either oral vancomycin or oral can be de-escalated to a standard regimen for nonse- fidaxomicin. vere disease. . Oral metronidazole may be used for an initial episode of nonsevere Clostridioides dfficile infection if vanco Bibliography J Viasus D, Vecino-Moreno M, De La Hoz JM, et al. Antibiotic stewardship UI mycin and fidaxomicin are unavailable or intolerable. in community-acquired pneumonia. Expert Rev Anti Infect Ther. { (D = 2017;15:351-359. [PMIO' zeoOzstgl doi:10.1080/14787210.2017. UI r274232 Bibtiography o, J McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for EL Clostridium difficile infection in adults and children: 2017 update by the n rI Infectious Diseases Society of America (IDSA) and Society for Healthcare * Epidemiologz of America (SHEA). Clin Infect Dis. 2018;66987-994. Item 12 Answer: A ll? IPMIO, 29562266) doi:10.1093 /cidl ciyl49 Ed ucationa I Objective: Treat secondary syphilis. (D UI A single dose of benzathine penicillin is the most appropri- tr Item 11 Answer: D Ed u cati on a I O bj ective : De-escalate antimicrobial therapy ate treatment for this patient who has secondary syphilis, which presented as a rash that is now resolving (Option A). The clinical manifestations of secondary syphilis can resolve in a patient hospitalized for severe community-acquired without treatment. Systemic symptoms and generalized pneumonia. lymphadenopathy are common, and epitrochlear lymph The most appropriate treatment is to discontinue the current nodes are characteristic. The absence of a history of genital treatment regimen and start levofloxacin (Option D). This or oral ulcers does not exclude the possibility of syphilis patient was critically ill, and his history of recent hospitaliza- because chancres are painless and may heal spontaneously tion for severe pneumonia increased the risk of community- without being noticed. Because the patient has a docu acquired pneumonia (CAP) caused by methicillin resistant mented history of syphilis, it is expected that an enzyme Staphylococcus aureus (MRSA) or Pseudomonos: he needed immunoassay result would remain positive; however, the empiric therapy for these organisms initially, althougl-r cov- signiflcant increase in the rapid plasma reagin (RPR) titer erage for Legionello and other fastidious organisms was not indicates a new infection. In this transgender woman at excluded. Therefore, the initial empiric regimen of vanco- high risk for STI, if she were unlikely to return for follow up, mycin, cefepime, and azithromycin was a reasonable choice. the clinical presentation would support providing empiric With negative blood and sputum cultures at 48 hours. the therapy for syphilis before laboratory results returned. This likelihood of infection with one of these agents is low. and patient should be counseled about the risk for STIs related antibiotics can be de-escalated to one of the standard reg- to unprotected oral sex, and condoms and dental dams imens for CAP in hospitalized patients. Additionally, the should be recommended to reduce this risk. The patient patient has improved enough to be transferred outside of the should have follow-up syphilis serologz testing at 6 and ICU, so it is safe to transition to a regimen for nonsevere pneu- 12 months, with an expected four-fold decrease in the RPR monia. Levofloxacin monotherapy, or combination therapy titer by 12 months. with a B-lactam and macrolide regimen. would be an appro- The three-dose regimen of benzathine penicillin priate choice. Levofloxacin monotherapy has the advantage of (Option B) is used to treat late-latent syphilis or syphilis of being an oral regimen, so if the patient were to be discharged unknown duration. before completing 5 days of therapy, he could continue this Data support the use of ceftriaxone (Option C) to man- antibiotic at home. age neurosyphilis in patients who are allergic to penicillin; Continuing any components of the initial antibiotic however, it is not recommended for syphilis in any other regimen (vancomycin. cefepime, or azithromycin) would be setting. overly broad coverage after the negative culture results for Doxycycline (Option D) is an alternate therapy for all resistant organisms (MRSA and Pseudctmonas) and would forms of syphilis with the exception of neurosyphilis, and not be indicated from an antibiotic stewardship perspective a l4-day course would be appropriate for management of (Option A, B, E). secondary syphilis; however, doxycycline should only be Although the Legionello antigen result lvas negative, used in patients with a penicillin allergr or if benzathine this test only covers one serogroup, ancl other pathogens penicillin is unavailable.

tr Item 11 Answer: D Ed u cati on a I O bj ective : De-escalate antimicrobial therapy ate treatment for this patient who has secondary syphilis, which presented as a rash that is now resolving (Option A). The clinical manifestations of secondary syphilis can resolve in a patient hospitalized for severe community-acquired without treatment. Systemic symptoms and generalized pneumonia. lymphadenopathy are common, and epitrochlear lymph The most appropriate treatment is to discontinue the current nodes are characteristic. The absence of a history of genital treatment regimen and start levofloxacin (Option D). This or oral ulcers does not exclude the possibility of syphilis patient was critically ill, and his history of recent hospitaliza- because chancres are painless and may heal spontaneously tion for severe pneumonia increased the risk of community- without being noticed. Because the patient has a docu acquired pneumonia (CAP) caused by methicillin resistant mented history of syphilis, it is expected that an enzyme Staphylococcus aureus (MRSA) or Pseudomonos: he needed immunoassay result would remain positive; however, the empiric therapy for these organisms initially, althougl-r cov- signiflcant increase in the rapid plasma reagin (RPR) titer erage for Legionello and other fastidious organisms was not indicates a new infection. In this transgender woman at excluded. Therefore, the initial empiric regimen of vanco- high risk for STI, if she were unlikely to return for follow up, mycin, cefepime, and azithromycin was a reasonable choice. the clinical presentation would support providing empiric With negative blood and sputum cultures at 48 hours. the therapy for syphilis before laboratory results returned. This likelihood of infection with one of these agents is low. and patient should be counseled about the risk for STIs related antibiotics can be de-escalated to one of the standard reg- to unprotected oral sex, and condoms and dental dams imens for CAP in hospitalized patients. Additionally, the should be recommended to reduce this risk. The patient patient has improved enough to be transferred outside of the should have follow-up syphilis serologz testing at 6 and ICU, so it is safe to transition to a regimen for nonsevere pneu- 12 months, with an expected four-fold decrease in the RPR monia. Levofloxacin monotherapy, or combination therapy titer by 12 months. with a B-lactam and macrolide regimen. would be an appro- The three-dose regimen of benzathine penicillin priate choice. Levofloxacin monotherapy has the advantage of (Option B) is used to treat late-latent syphilis or syphilis of being an oral regimen, so if the patient were to be discharged unknown duration. before completing 5 days of therapy, he could continue this Data support the use of ceftriaxone (Option C) to man- antibiotic at home. age neurosyphilis in patients who are allergic to penicillin; Continuing any components of the initial antibiotic however, it is not recommended for syphilis in any other regimen (vancomycin. cefepime, or azithromycin) would be setting. overly broad coverage after the negative culture results for Doxycycline (Option D) is an alternate therapy for all resistant organisms (MRSA and Pseudctmonas) and would forms of syphilis with the exception of neurosyphilis, and not be indicated from an antibiotic stewardship perspective a l4-day course would be appropriate for management of (Option A, B, E). secondary syphilis; however, doxycycline should only be Although the Legionello antigen result lvas negative, used in patients with a penicillin allergr or if benzathine this test only covers one serogroup, ancl other pathogens penicillin is unavailable. 144

Answers and Criti ques XEY POI T{T KEY POIilT5 . The recommended treatment for secondary syphilis . Empiric treatment of necrotizing fasciitis consists of is a single dose of intramuscular benzathine peni_ vancomycin, daptomycin, or linezolid plus piperacillin_ cillin. tazobactam, a carbapenem, ceftriaxone plus metroni- dazole, or a fluoroquinolone plus metronidazole. Bibliography o Doxycycline plus ceftazidime is recommended for Workowski KA, Bolan GA; Centers for Disease Control and prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR treatment of Vibrio u ulnifi cus- associated necrotizing Recomm Rep. 2015;64:1-137. [PMID : 26042815] fasciitis. Bibliography

XEY POI T{T KEY POIilT5 . The recommended treatment for secondary syphilis . Empiric treatment of necrotizing fasciitis consists of is a single dose of intramuscular benzathine peni_ vancomycin, daptomycin, or linezolid plus piperacillin_ cillin. tazobactam, a carbapenem, ceftriaxone plus metroni- dazole, or a fluoroquinolone plus metronidazole. Bibliography o Doxycycline plus ceftazidime is recommended for Workowski KA, Bolan GA; Centers for Disease Control and prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR treatment of Vibrio u ulnifi cus- associated necrotizing Recomm Rep. 2015;64:1-137. [PMID : 26042815] fasciitis. Bibliography tr Item 13 Answer: A E d u cat o n a I O bj e ct ve : Treat Wbrio u ulnifictrs-,associated i i Stevens DL, Bisno AL, Chambers HFi, Dellinger EB Goldstein EJ, Gorbach SL. et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. CIin Infect Dis. ZOf+r UI €, J necrotizing fasciitis. 59 : e10 - 52. [pti,llo' 2497 3422] doi: 10. 1093 /c id I ciu4 44 ET a- f .I Doxycycline plus ceftazidime (Option A) is the most L U appropriate antibiotic regimen for this patient with Item 14 Answer: C -, ? Vibrio uulnifictts associated necrotizing fasciitis. Clues to a IE potential necrotizing skin and soft tissue infection include Educational Objective: Evaluate a patient for deficiency UI L in terminal complement levels. (u systemic toxicity with fever chills, tachycardia, tachypnea, and hypotension. the appearance of hemorrhagic bullous This patient should be evaluated for a defect in terminal com- = UI ? lesions is a classic cutaneous manif'estation of V. uulnificus plement level by testing the total hemolytic complement - infection. Patients who are immunocompromised, partic (CUro; level (Option C). She has a personal history of dissem- ularly with liver disease, are at increased risk for infectior-r inated gonorrhea and a family history of meningococcemia. with this gram-negative bacillus. Infection usually occurs The terminal complement pathway includes C5 to C9, which after consumption of raw shellfish. such as oysters, or skin together form the membrane attack complex, or MAC. The trauma incurred in warm sea waters, such as the Gulf of MAC plays a key role in host immunity against lfeisserio Mexico, or brackish water. In addition to emergent surgical species, and deflciency of a late complement component is exploration an d debridement, doxycycli ne plus ceftazi dime associated with an up to 10,000-fold increased risk of menin- is recommended. gococcal disease. Counterintuitively, although patients with Empiric antibiotic treatment for necrotizing fasciitis terminal complement deflciencies are at increased risk of includes broad-spectrum coverage fbr aerobic and anaer disseminated l{eisserio infection, including meningococcal obic organisms (including methicillin resistant Staphyk> meningitis, these tend to be relatively mild and are rarely coccus aureus) and consists of vancomycin, daptomycin, or life-threatening. A personal history of recurrent lfeisserio linezolid plus piperacillin-tazobactam, a carbapenem, cef infection or a history of lfeisserio infections among multiple triaxone plus metronidazole, or a fluoroquinolone plus met, family members is an indication to test for terminal com- ronidazole. Some experts also recommend adding empiric plement deflciency. Some studies suggest up to a2O% preva- clindamycin because of its suppression of toxin production lence of complement deflciency among patients with invasive by staphylococci and streptococci. meningococcal disease, justifizing screening at the time of ini Nafcillin and rifampin (Option B) provide coverage tial presentation, regardless of family history. In patients with against rnethicillin-sensitive S. oureus, particularly in the a low CHro level, more specialized testing can be performed setting of prosthetic joint infections, but would not be eff'ec to identif,i the speciflc protein deflciency. Patients with defi tive against V. uulnificus. ciencies in terminal complement levels should receive the Penicillin plus clindamycin (Option C) is indicated ftrr conjugate and serogroup B meningococcal vaccines. antibiotic treatment of group A streptococcus (i.e., Sfrepto- Idiopathic CD4 lymphopenia is associated with coccus pyogenes) -associated necrotizing fasciitis. Although decreased T-cell function, and these patients are at risk for S. pyogenes is susceptible to penicillin. clindamycin is added the same opportunistic infections seen in patients with HIV because of its ability to suppress streptococcal toxin produc or AIDS, depending on the absolute level, but not l{eisserio tion and remains effective even in the presence of a high infections (Option A). inoculum of bacteria. If the aquatic pathogen Aeromonas Selective IgA deficiency is the most common cause of hydrophila is the cause of necrotizing fasciitis, then a regi- primary immunodeflciency but is frequently asymptomatic men consisting of doxycycline plus ciprofloxacin should be (Option B). Recurrent sinus or pulmonary infections are used. the most common infectious complications of selective IgA Vancomycin plus clindamycin (Option D) would deflciency, not Neisserio infections. be effective in necrotizing fasciitis with associated toxic Not testing further would be inappropriate for this shock caused by MRSA but would not be active against patient with a personal and family history of l{eisserio V. uulnificus. infection (Option D). The identiflcation of late complement

tr Item 13 Answer: A E d u cat o n a I O bj e ct ve : Treat Wbrio u ulnifictrs-,associated i i Stevens DL, Bisno AL, Chambers HFi, Dellinger EB Goldstein EJ, Gorbach SL. et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. CIin Infect Dis. ZOf+r UI €, J necrotizing fasciitis. 59 : e10 - 52. [pti,llo' 2497 3422] doi: 10. 1093 /c id I ciu4 44 ET a- f .I Doxycycline plus ceftazidime (Option A) is the most L U appropriate antibiotic regimen for this patient with Item 14 Answer: C -, ? Vibrio uulnifictts associated necrotizing fasciitis. Clues to a IE potential necrotizing skin and soft tissue infection include Educational Objective: Evaluate a patient for deficiency UI L in terminal complement levels. (u systemic toxicity with fever chills, tachycardia, tachypnea, and hypotension. the appearance of hemorrhagic bullous This patient should be evaluated for a defect in terminal com- = UI ? lesions is a classic cutaneous manif'estation of V. uulnificus plement level by testing the total hemolytic complement - infection. Patients who are immunocompromised, partic (CUro; level (Option C). She has a personal history of dissem- ularly with liver disease, are at increased risk for infectior-r inated gonorrhea and a family history of meningococcemia. with this gram-negative bacillus. Infection usually occurs The terminal complement pathway includes C5 to C9, which after consumption of raw shellfish. such as oysters, or skin together form the membrane attack complex, or MAC. The trauma incurred in warm sea waters, such as the Gulf of MAC plays a key role in host immunity against lfeisserio Mexico, or brackish water. In addition to emergent surgical species, and deflciency of a late complement component is exploration an d debridement, doxycycli ne plus ceftazi dime associated with an up to 10,000-fold increased risk of menin- is recommended. gococcal disease. Counterintuitively, although patients with Empiric antibiotic treatment for necrotizing fasciitis terminal complement deflciencies are at increased risk of includes broad-spectrum coverage fbr aerobic and anaer disseminated l{eisserio infection, including meningococcal obic organisms (including methicillin resistant Staphyk> meningitis, these tend to be relatively mild and are rarely coccus aureus) and consists of vancomycin, daptomycin, or life-threatening. A personal history of recurrent lfeisserio linezolid plus piperacillin-tazobactam, a carbapenem, cef infection or a history of lfeisserio infections among multiple triaxone plus metronidazole, or a fluoroquinolone plus met, family members is an indication to test for terminal com- ronidazole. Some experts also recommend adding empiric plement deflciency. Some studies suggest up to a2O% preva- clindamycin because of its suppression of toxin production lence of complement deflciency among patients with invasive by staphylococci and streptococci. meningococcal disease, justifizing screening at the time of ini Nafcillin and rifampin (Option B) provide coverage tial presentation, regardless of family history. In patients with against rnethicillin-sensitive S. oureus, particularly in the a low CHro level, more specialized testing can be performed setting of prosthetic joint infections, but would not be eff'ec to identif,i the speciflc protein deflciency. Patients with defi tive against V. uulnificus. ciencies in terminal complement levels should receive the Penicillin plus clindamycin (Option C) is indicated ftrr conjugate and serogroup B meningococcal vaccines. antibiotic treatment of group A streptococcus (i.e., Sfrepto- Idiopathic CD4 lymphopenia is associated with coccus pyogenes) -associated necrotizing fasciitis. Although decreased T-cell function, and these patients are at risk for S. pyogenes is susceptible to penicillin. clindamycin is added the same opportunistic infections seen in patients with HIV because of its ability to suppress streptococcal toxin produc or AIDS, depending on the absolute level, but not l{eisserio tion and remains effective even in the presence of a high infections (Option A). inoculum of bacteria. If the aquatic pathogen Aeromonas Selective IgA deficiency is the most common cause of hydrophila is the cause of necrotizing fasciitis, then a regi- primary immunodeflciency but is frequently asymptomatic men consisting of doxycycline plus ciprofloxacin should be (Option B). Recurrent sinus or pulmonary infections are used. the most common infectious complications of selective IgA Vancomycin plus clindamycin (Option D) would deflciency, not Neisserio infections. be effective in necrotizing fasciitis with associated toxic Not testing further would be inappropriate for this shock caused by MRSA but would not be active against patient with a personal and family history of l{eisserio V. uulnificus. infection (Option D). The identiflcation of late complement 145

Answers and Critiques deflciency has therapeutic implications because these mellitus, and acidosis. Mucormycosis has flve major clini- patients should receive the conjugate and serogroup B cal forms: (1) rhinocerebral; (2) pulmonary; (3) abdominal, meningococcal vaccines. pelvic, gastric, gastrointestinal; (4) primary cutaneous; and (5) disseminated. Because laboratory studies are nonspeciflc, KEY POIl{IS diagnosis relies on a high index of suspicion in a patient . A personal history of recurrent lVeisserio infection or with appropriate risk factors and evidence of tissue invasion, a history of Neisseric infections among multiple fam- including the characteristic appearance of broad. nonseptate ily members is an indication to screen for terminal hyphae u,ith acute-angle branches. complement deficiency by measuring total hemolytic KEY POIlITS complement (CHso) level. . Blastomycosis is a dimorphic, round, budding yeast o Patients with terminal complement deficiency should that most often manifests as a primary pulmonary receive the conjugate and serogroup B meningococcal infection in immunocompetent persons. D vaccines. t=t o Blastomycosis is found primarily along the Mississippi € .D and Ohio River valleys but can be found as far north as rl Bibliography l,l Devonshire AL, Makhija M. Approach to primary immunodeficiency. Allerry Wisconsin and Minnesota and as far south as Florida. o, - a Asthma Proc. 2019;40:165 469. [PMID: 31OSOSSO] doi:10.2500/aap. 2019.40.4273 n Bibliography rl McBride JA, Gauthier GM, Klein BS. Clinical manifestations and treatment I' i of blastomycosis. CIin Chest Med. 2017;38:435 449. IPMID: zffiglqall It-a Item 15 Answer: A - (D Ed u cati o n a I O bj ective : Diagnose blastomycosis. doi:10.1016 /j.ccm.2017.04. 006

deflciency has therapeutic implications because these mellitus, and acidosis. Mucormycosis has flve major clini- patients should receive the conjugate and serogroup B cal forms: (1) rhinocerebral; (2) pulmonary; (3) abdominal, meningococcal vaccines. pelvic, gastric, gastrointestinal; (4) primary cutaneous; and (5) disseminated. Because laboratory studies are nonspeciflc, KEY POIl{IS diagnosis relies on a high index of suspicion in a patient . A personal history of recurrent lVeisserio infection or with appropriate risk factors and evidence of tissue invasion, a history of Neisseric infections among multiple fam- including the characteristic appearance of broad. nonseptate ily members is an indication to screen for terminal hyphae u,ith acute-angle branches. complement deficiency by measuring total hemolytic KEY POIlITS complement (CHso) level. . Blastomycosis is a dimorphic, round, budding yeast o Patients with terminal complement deficiency should that most often manifests as a primary pulmonary receive the conjugate and serogroup B meningococcal infection in immunocompetent persons. D vaccines. t=t o Blastomycosis is found primarily along the Mississippi € .D and Ohio River valleys but can be found as far north as rl Bibliography l,l Devonshire AL, Makhija M. Approach to primary immunodeficiency. Allerry Wisconsin and Minnesota and as far south as Florida. o, - a Asthma Proc. 2019;40:165 469. [PMID: 31OSOSSO] doi:10.2500/aap. 2019.40.4273 n Bibliography rl McBride JA, Gauthier GM, Klein BS. Clinical manifestations and treatment I' i of blastomycosis. CIin Chest Med. 2017;38:435 449. IPMID: zffiglqall It-a Item 15 Answer: A - (D Ed u cati o n a I O bj ective : Diagnose blastomycosis. doi:10.1016 /j.ccm.2017.04. 006 UI

deflciency has therapeutic implications because these mellitus, and acidosis. Mucormycosis has flve major clini- patients should receive the conjugate and serogroup B cal forms: (1) rhinocerebral; (2) pulmonary; (3) abdominal, meningococcal vaccines. pelvic, gastric, gastrointestinal; (4) primary cutaneous; and (5) disseminated. Because laboratory studies are nonspeciflc, KEY POIl{IS diagnosis relies on a high index of suspicion in a patient . A personal history of recurrent lVeisserio infection or with appropriate risk factors and evidence of tissue invasion, a history of Neisseric infections among multiple fam- including the characteristic appearance of broad. nonseptate ily members is an indication to screen for terminal hyphae u,ith acute-angle branches. complement deficiency by measuring total hemolytic KEY POIlITS complement (CHso) level. . Blastomycosis is a dimorphic, round, budding yeast o Patients with terminal complement deficiency should that most often manifests as a primary pulmonary receive the conjugate and serogroup B meningococcal infection in immunocompetent persons. D vaccines. t=t o Blastomycosis is found primarily along the Mississippi € .D and Ohio River valleys but can be found as far north as rl Bibliography l,l Devonshire AL, Makhija M. Approach to primary immunodeficiency. Allerry Wisconsin and Minnesota and as far south as Florida. o, - a Asthma Proc. 2019;40:165 469. [PMID: 31OSOSSO] doi:10.2500/aap. 2019.40.4273 n Bibliography rl McBride JA, Gauthier GM, Klein BS. Clinical manifestations and treatment I' i of blastomycosis. CIin Chest Med. 2017;38:435 449. IPMID: zffiglqall It-a Item 15 Answer: A - (D Ed u cati o n a I O bj ective : Diagnose blastomycosis. doi:10.1016 /j.ccm.2017.04. 006 UI The patient has pulmonary blastomycosis (Option A). In the Item 16 Answer: B United States, blastomycosis is found primarily along the Educational Objective: Treat facial nerve palsy caused Mississippi and Ohio River valleys but can be found as far by Lyme disease. north as Wisconsin and Minnesota and as far south as Florida. Exposure to soil is the most commonly identifled risk factor. This patient has isolated right facial nerve palsy caused by The organism is typically diagnosed on respiratory secretions Borrelia, and doxycycline for L4 to 2l days is the treatment demonstrating large, round, budding yeast, with the mother of choice (Option B). Lyme disease accounts for up to 25o1, of cell connecting to the daughter cell. Serologic assays can also cases of facial nerve palsy in endemic areas during summer be used if stains and cultures are negative. In addition to the months. Facial nerve palsy caused by neuroborreliosis can respiratory tract, infection also occurs commonly in skin, be unilateral or bilateral and may present alone or overlap bones, joints, and the urinary tract. Most infections are sub- with meningitis. Without previously documented or con acute or chronic and can be treated with oral azole antifungals current erythema migrans, laboratory testing is necessary to such as itraconazole. distinguish facial palsy resulting from Lyme disease from Bell Signs and symptoms of focal Candidainfection (Option palsy (idiopathic peripheral facial nerve palsy). Laboratory B) depend on the site involved (abscess or peritonitis in the conflrmation of Lyme disease employs a two tiered serologic peritoneum, empyema in the pleural cavity, or pyelonephri- algorithm. In patients with a positive or equivocal screening tis in the kidneys). Other forms of invasive infection include enzyme immunoassay (EIA) or indirect fluorescent antibody meningitis, osteomyelitis, septic arthritis, and endocarditis. test, a secondary conflrmatory EIA (previously, Western blot Although often found in the respiratory tract, Candida spe- was most common) is performed. A positive IgM antibody cies rarely cause infections there and are likely the result of with a negative IgG antibody can occur early in the course of colonization. In Gram stained smears, Candida appears as infection when insufficient time has passed for IgG serocon- gram-positive budding yeast cells or pseudohyphae. version, as is the case in this patient. The IgG almost invariably Coccidioides immitis refers to isolates from California. becomes positive within 4 weeks of symptom onset; after this and C. posodosii refers to isolates from all other endemic time period, a negative IgG Western blot excludes a diagnosis areas, including Arizona, New Mexico, western Texas, north of Lyme disease. A sequential EIA test that reacts with a dif- ern Mexico, and parts of Central and South America. Coccid- ferent bacterial epitope has been approved as an alternative ioidomycosis (Option C) may manifest as acute or chronic conflrmatory test and may eventually replace the Western blot pulmonary infection, cutaneous infection, meningitis, as the preferred assay. or musculoskeletal infection. Spherules are the most com- In this patient with no clinical evidence of meningo mon morphologic form of Coccidioides seen in clinical encephalitis or myelitis, a lumbar puncture is unlikely to specimens. provide additional information (Option A). Mucormycosis (Option D) is the third most frequent Early use of glucocorticoids has been proven to decrease cause of invasive fungal infections in immunocompromised long-term neurologic dysfunction in Bell palsy, and a l-week persons, but it is rarely seen in immunocompetent persons. course of prednisone would be appropriate if Lyme disease Particularly at risk are patients with neutropenia, diabetes was excluded (Option C). Small studies evaluating the role of

The patient has pulmonary blastomycosis (Option A). In the Item 16 Answer: B United States, blastomycosis is found primarily along the Educational Objective: Treat facial nerve palsy caused Mississippi and Ohio River valleys but can be found as far by Lyme disease. north as Wisconsin and Minnesota and as far south as Florida. Exposure to soil is the most commonly identifled risk factor. This patient has isolated right facial nerve palsy caused by The organism is typically diagnosed on respiratory secretions Borrelia, and doxycycline for L4 to 2l days is the treatment demonstrating large, round, budding yeast, with the mother of choice (Option B). Lyme disease accounts for up to 25o1, of cell connecting to the daughter cell. Serologic assays can also cases of facial nerve palsy in endemic areas during summer be used if stains and cultures are negative. In addition to the months. Facial nerve palsy caused by neuroborreliosis can respiratory tract, infection also occurs commonly in skin, be unilateral or bilateral and may present alone or overlap bones, joints, and the urinary tract. Most infections are sub- with meningitis. Without previously documented or con acute or chronic and can be treated with oral azole antifungals current erythema migrans, laboratory testing is necessary to such as itraconazole. distinguish facial palsy resulting from Lyme disease from Bell Signs and symptoms of focal Candidainfection (Option palsy (idiopathic peripheral facial nerve palsy). Laboratory B) depend on the site involved (abscess or peritonitis in the conflrmation of Lyme disease employs a two tiered serologic peritoneum, empyema in the pleural cavity, or pyelonephri- algorithm. In patients with a positive or equivocal screening tis in the kidneys). Other forms of invasive infection include enzyme immunoassay (EIA) or indirect fluorescent antibody meningitis, osteomyelitis, septic arthritis, and endocarditis. test, a secondary conflrmatory EIA (previously, Western blot Although often found in the respiratory tract, Candida spe- was most common) is performed. A positive IgM antibody cies rarely cause infections there and are likely the result of with a negative IgG antibody can occur early in the course of colonization. In Gram stained smears, Candida appears as infection when insufficient time has passed for IgG serocon- gram-positive budding yeast cells or pseudohyphae. version, as is the case in this patient. The IgG almost invariably Coccidioides immitis refers to isolates from California. becomes positive within 4 weeks of symptom onset; after this and C. posodosii refers to isolates from all other endemic time period, a negative IgG Western blot excludes a diagnosis areas, including Arizona, New Mexico, western Texas, north of Lyme disease. A sequential EIA test that reacts with a dif- ern Mexico, and parts of Central and South America. Coccid- ferent bacterial epitope has been approved as an alternative ioidomycosis (Option C) may manifest as acute or chronic conflrmatory test and may eventually replace the Western blot pulmonary infection, cutaneous infection, meningitis, as the preferred assay. or musculoskeletal infection. Spherules are the most com- In this patient with no clinical evidence of meningo mon morphologic form of Coccidioides seen in clinical encephalitis or myelitis, a lumbar puncture is unlikely to specimens. provide additional information (Option A). Mucormycosis (Option D) is the third most frequent Early use of glucocorticoids has been proven to decrease cause of invasive fungal infections in immunocompromised long-term neurologic dysfunction in Bell palsy, and a l-week persons, but it is rarely seen in immunocompetent persons. course of prednisone would be appropriate if Lyme disease Particularly at risk are patients with neutropenia, diabetes was excluded (Option C). Small studies evaluating the role of 146

Answers and Criti ques concomitant antibiotic and glucocorticoid therapy for facial typically report watery diarrhea that is greasy, floating, and palsy caused by Lyme disease suggest either no effect or a foul smelling; flatul€nCe; bloating; nausea; and crampy detrimental eflect with combination therapy. abdominal pain. Fever is uncommon. HUS is not associated Parenteral therapy with ceftriaxone is reserved for with Giord ia lamblia infections. patients with meningoencephalitis or myelitis, which is not Noroviruses (Option D) are the most common cause of present in this patient (Option D). For mildly ill patients gastroenteritis in the United States, aflecting all ages. Trans- with isolated peripheral nerve involvement, doxycycline is mission from person to person is primarily by the fecal-oral equally effective and avoids the cost, inconvenience, and route. The incubation period is typically less than 2 days, and potential risks of parenteral therapy. infected patients usually have self-limited watery diarrhea, IEY POIl{TS nausea, vomiting, and fever but do not develop HUS.

concomitant antibiotic and glucocorticoid therapy for facial typically report watery diarrhea that is greasy, floating, and palsy caused by Lyme disease suggest either no effect or a foul smelling; flatul€nCe; bloating; nausea; and crampy detrimental eflect with combination therapy. abdominal pain. Fever is uncommon. HUS is not associated Parenteral therapy with ceftriaxone is reserved for with Giord ia lamblia infections. patients with meningoencephalitis or myelitis, which is not Noroviruses (Option D) are the most common cause of present in this patient (Option D). For mildly ill patients gastroenteritis in the United States, aflecting all ages. Trans- with isolated peripheral nerve involvement, doxycycline is mission from person to person is primarily by the fecal-oral equally effective and avoids the cost, inconvenience, and route. The incubation period is typically less than 2 days, and potential risks of parenteral therapy. infected patients usually have self-limited watery diarrhea, IEY POIl{TS nausea, vomiting, and fever but do not develop HUS. . Lyme disease accounts for up to 25% of cases of facial I(EY POITITS nerye palsy in endemic areas during summer months. o Enterohemorrhagic Escherichio. coliinfection is not a 6' o Doxycycline is the treatment of choice for patients typically associated with fever, a distinguishing feature J from other causes of bloody diarrhea. ET with isolated facial nerve palsy and positive enzyme .= immunoassay results for Lyme disease. . Enterohemorrhagic Escherichia coliproduces a Shiga L (J toxin that can cause hemorrhagic colitis with develop- -tE Bibliography ment of hemolytic uremic syndrome, which manifests IE Halperin JJ. Lyme neuroborreliosis. Curr Opin Infect Dis. 2019;32:259 264 ta as microangiopathic hemoly.tic anemia, thrombocyto- L lPMIl, 309210861 doi:10.i097IQCO.0000000000000s4s $ penia, and kidney injury. E 1 E Bibliography Item 17 Answer: B Kremer Hovinga JA, Heeb SR. Skowronska M, et al. Pathophysiologr of thrombotic thrombocytopenic purpura and hemolytic uremic syn Educational Objective: Diagnose hemolytic uremic syn- drome. J Thromb Haemost. 2O1B;16:618 629. [PMID: ZSSSOSOO] doi:10. drome caused by Shiga toxin-producing Escherichiacoli. 1111/jth.13956

. Lyme disease accounts for up to 25% of cases of facial I(EY POITITS nerye palsy in endemic areas during summer months. o Enterohemorrhagic Escherichio. coliinfection is not a 6' o Doxycycline is the treatment of choice for patients typically associated with fever, a distinguishing feature J from other causes of bloody diarrhea. ET with isolated facial nerve palsy and positive enzyme .= immunoassay results for Lyme disease. . Enterohemorrhagic Escherichia coliproduces a Shiga L (J toxin that can cause hemorrhagic colitis with develop- -tE Bibliography ment of hemolytic uremic syndrome, which manifests IE Halperin JJ. Lyme neuroborreliosis. Curr Opin Infect Dis. 2019;32:259 264 ta as microangiopathic hemoly.tic anemia, thrombocyto- L lPMIl, 309210861 doi:10.i097IQCO.0000000000000s4s $ penia, and kidney injury. E 1 E Bibliography Item 17 Answer: B Kremer Hovinga JA, Heeb SR. Skowronska M, et al. Pathophysiologr of thrombotic thrombocytopenic purpura and hemolytic uremic syn Educational Objective: Diagnose hemolytic uremic syn- drome. J Thromb Haemost. 2O1B;16:618 629. [PMID: ZSSSOSOO] doi:10. drome caused by Shiga toxin-producing Escherichiacoli. 1111/jth.13956 Enterohemorrhagic Escherichia coli (EHEC) strains (Option Item 18 B), most commonly Ol57:H7, produce a Shiga toxin (i.e., Shiga toxin-producing E. coli, or STEC) that can cause hemorrhagic colitis with development of hemolytic uremic syndrome Answer: D Educational Objective: Evaluate a postoperative patient tr for a catheter-associated urinary tract infection. (HUS), as in this patient. These bacteria are transmitted by ingestion of undercooked beel usually hamburger, or fecally Clinical observation is tl-re most appropriate rnanagement contaminated food and water, including recreational lake (Option D). The patient's new onset fever supgested the possi' water; fecal-oral transmission through exposure to infected bility of an infectior-r. h-r the course of evaluating the infection, animals is also possible. The incubation period is 3 to 4 days, a urinalysis \\as obtair-red. which rerealed pyuria. Holvever. and patients typically have visibly bloody diarrhea, crampy the presence of pyuria is a nonspecific finding, is not a symp abdominal pain, and no fever; the latter is a distinguishing tom of'catheter associated urinary tract inf'ection (CAUTI). feature from other causes of bloody diarrhea. HUS develops and should not be interpreted as an indication fbr antibiotic in less than 10'7, of patients infected with EHEC and man- treatment. The next step should be to determine if'the patient ifests as microangiopathic hemolytic anemia (schistocytes has ar-ry additional eviclence-based symptoms of CAUTI such on peripheral blood smear), thrombocfiopenia, and acute as hernaturia. rigors, flar-rk pain, pelvic discornfbtl, or supra- kidney injury. pubic painr after renroval of'the urinary catheter. the presence Cyclospora infections (Option A) are typically acquired of urgenclr frequency. or dysuria should be determined as after consumption of food or water that is fecally contami well. Tl-ris patient had no synptoms of CAUTI other than fever. nated with Cyclosporo oocysts. In the United States, many The next question should be whether the patient had any of these infections have been traced to imported fresh pro- other diagnosis that could account for the f'ever. In this case. duce from tropical and subtropical areas or have occurred the normal physical eramination and stability of the vital in travelers to endemic areas. Infected patients typically signs otl-rer tl-ran temperature suggest that the fever could be present with watery diarrhea, decreased appetite, weight a postoperative fever. Postoperative fever is mediated by cyto loss, crampy abdominal pain, bloating, flatulence, nausea, kines, tumor necrosis factor, and interferon-yreleased follort, fatigue, and (sometimes) fever. HUS is not associated with ing surgical stress. The median time to peak temperature is Cy closp ora infections. 11 hours, and half of'patients have a temperature erceeding Giardia lamblia (Option C) is the most common par- 38 'C (tOO.+ "F). Most fevers resulting fiont surgical stress asitic pathogen in the United States. Cysts from infected resolve spontaneously after ser,eral hours; those related to animals are excreted in stool into reservoirs of natural fresh slrrgery fbr severe trauma may persist for days. water, and subsequent ingestion of contaminated water (or In the absence of an1' sign other than f'ever and a rea food) can lead to human infection. Symptomatic patients sonable explanation fbr the patient's tenlperature elevation,

Enterohemorrhagic Escherichia coli (EHEC) strains (Option Item 18 B), most commonly Ol57:H7, produce a Shiga toxin (i.e., Shiga toxin-producing E. coli, or STEC) that can cause hemorrhagic colitis with development of hemolytic uremic syndrome Answer: D Educational Objective: Evaluate a postoperative patient tr for a catheter-associated urinary tract infection. (HUS), as in this patient. These bacteria are transmitted by ingestion of undercooked beel usually hamburger, or fecally Clinical observation is tl-re most appropriate rnanagement contaminated food and water, including recreational lake (Option D). The patient's new onset fever supgested the possi' water; fecal-oral transmission through exposure to infected bility of an infectior-r. h-r the course of evaluating the infection, animals is also possible. The incubation period is 3 to 4 days, a urinalysis \\as obtair-red. which rerealed pyuria. Holvever. and patients typically have visibly bloody diarrhea, crampy the presence of pyuria is a nonspecific finding, is not a symp abdominal pain, and no fever; the latter is a distinguishing tom of'catheter associated urinary tract inf'ection (CAUTI). feature from other causes of bloody diarrhea. HUS develops and should not be interpreted as an indication fbr antibiotic in less than 10'7, of patients infected with EHEC and man- treatment. The next step should be to determine if'the patient ifests as microangiopathic hemolytic anemia (schistocytes has ar-ry additional eviclence-based symptoms of CAUTI such on peripheral blood smear), thrombocfiopenia, and acute as hernaturia. rigors, flar-rk pain, pelvic discornfbtl, or supra- kidney injury. pubic painr after renroval of'the urinary catheter. the presence Cyclospora infections (Option A) are typically acquired of urgenclr frequency. or dysuria should be determined as after consumption of food or water that is fecally contami well. Tl-ris patient had no synptoms of CAUTI other than fever. nated with Cyclosporo oocysts. In the United States, many The next question should be whether the patient had any of these infections have been traced to imported fresh pro- other diagnosis that could account for the f'ever. In this case. duce from tropical and subtropical areas or have occurred the normal physical eramination and stability of the vital in travelers to endemic areas. Infected patients typically signs otl-rer tl-ran temperature suggest that the fever could be present with watery diarrhea, decreased appetite, weight a postoperative fever. Postoperative fever is mediated by cyto loss, crampy abdominal pain, bloating, flatulence, nausea, kines, tumor necrosis factor, and interferon-yreleased follort, fatigue, and (sometimes) fever. HUS is not associated with ing surgical stress. The median time to peak temperature is Cy closp ora infections. 11 hours, and half of'patients have a temperature erceeding Giardia lamblia (Option C) is the most common par- 38 'C (tOO.+ "F). Most fevers resulting fiont surgical stress asitic pathogen in the United States. Cysts from infected resolve spontaneously after ser,eral hours; those related to animals are excreted in stool into reservoirs of natural fresh slrrgery fbr severe trauma may persist for days. water, and subsequent ingestion of contaminated water (or In the absence of an1' sign other than f'ever and a rea food) can lead to human infection. Symptomatic patients sonable explanation fbr the patient's tenlperature elevation, 147

Answers and Critiques obtaining a urine culture (Option A) is not indicated. A pos- complicated pyelonephritis because of the increased rate of ffi resistance in common uropathogens. l*l 111vs urine culture would signify asymptomatic bacteriuria coNI f' r which antibiotics should not be prescribed. Trimethoprim-sulfamethoxazole (Option E) would not Repeating the urinalysis (Option B) and urine culture be an appropriate choice in this patient owing to high rates after catheter removal is unnecessary unless the patient of community resistance and her recent exposure to this develops signs or symptoms of a UTI. drug. Inappropriate antibiotic therapy fbr asymptomatic bac- Actir,e oral antibiotics can be substituted to complete teriuria can lead to development of antibiotic resistance and therapy in clinically stable patients who have reliable follow increases the risk of experiencing an adverse effect related up. Choices may include fluoroquinolones or trimethoprim- to the antibiotic. This patient has no need for empiric anti- sulfamethoxazole. B-Lactams (e. g.. amoxicillin-clavulanate, biotics (Option C). cephalexin, cefdinir, cefpodoxime proxetil) are an alternative but may be less efl'ective in eradication of the infection. Patients t(tY PolilTs rvith bacteremia who exhibit adequate clinical responses do J o Postoperative fever reaches a peak at ll hours following not require follow-up blood cultures or prolonged intravenous UI (D surgery and half of patients have a temperature therapy. = - exceeding 38'C (roo.+'P). UI g, KEY POIilTS -) . The presence of pyrrria is a nonspecific finding, is not a o Intravenous antimicrobial therapy with ceftriaxone CL symptom of catheter-associated urinary tract infection, n- (or another broad-spectrum cephalosporin or carba- and should not be interpreted as an indication for if. antibiotic treatment. penem) is appropriate initial treatment in patients .Et with complicated acute pyelonephritis who require = (D UI hospitalization. Bibliography Naik AD, Skelton F, Amspoker AB, et al. A fast and frugal algorithm to . Empiric intravenous fluoroquinolones are not recom- strengthen diagnosis and treatment decisions for catheter-associated mended for treatment of complicated pyelonephritis bacteriuria. PLoS One. 2077 ;12:e017 4415. [PM I D : ZASSOS:S] doi: 10. 1371 / journal.pone .O174415 in hospitalized patients.

obtaining a urine culture (Option A) is not indicated. A pos- complicated pyelonephritis because of the increased rate of ffi resistance in common uropathogens. l*l 111vs urine culture would signify asymptomatic bacteriuria coNI f' r which antibiotics should not be prescribed. Trimethoprim-sulfamethoxazole (Option E) would not Repeating the urinalysis (Option B) and urine culture be an appropriate choice in this patient owing to high rates after catheter removal is unnecessary unless the patient of community resistance and her recent exposure to this develops signs or symptoms of a UTI. drug. Inappropriate antibiotic therapy fbr asymptomatic bac- Actir,e oral antibiotics can be substituted to complete teriuria can lead to development of antibiotic resistance and therapy in clinically stable patients who have reliable follow increases the risk of experiencing an adverse effect related up. Choices may include fluoroquinolones or trimethoprim- to the antibiotic. This patient has no need for empiric anti- sulfamethoxazole. B-Lactams (e. g.. amoxicillin-clavulanate, biotics (Option C). cephalexin, cefdinir, cefpodoxime proxetil) are an alternative but may be less efl'ective in eradication of the infection. Patients t(tY PolilTs rvith bacteremia who exhibit adequate clinical responses do J o Postoperative fever reaches a peak at ll hours following not require follow-up blood cultures or prolonged intravenous UI (D surgery and half of patients have a temperature therapy. = - exceeding 38'C (roo.+'P). UI g, KEY POIilTS -) . The presence of pyrrria is a nonspecific finding, is not a o Intravenous antimicrobial therapy with ceftriaxone CL symptom of catheter-associated urinary tract infection, n- (or another broad-spectrum cephalosporin or carba- and should not be interpreted as an indication for if. antibiotic treatment. penem) is appropriate initial treatment in patients .Et with complicated acute pyelonephritis who require = (D UI hospitalization. Bibliography Naik AD, Skelton F, Amspoker AB, et al. A fast and frugal algorithm to . Empiric intravenous fluoroquinolones are not recom- strengthen diagnosis and treatment decisions for catheter-associated mended for treatment of complicated pyelonephritis bacteriuria. PLoS One. 2077 ;12:e017 4415. [PM I D : ZASSOS:S] doi: 10. 1371 / journal.pone .O174415 in hospitalized patients. Bibliography Item 19 tr Answer: B Ed ucationa I Objective: Treat acute pyelonephritis. Johnson JR, Russo TA. Acute pyelonephritis in adults. N Engl J Med. 2018;378: 48-59. [Pl,llO' ZSZgetSS]

Bibliography Item 19 tr Answer: B Ed ucationa I Objective: Treat acute pyelonephritis. Johnson JR, Russo TA. Acute pyelonephritis in adults. N Engl J Med. 2018;378: 48-59. [Pl,llO' ZSZgetSS] Intravenous antimicrobial therapy with ceftriaxone (Option B) or another broad-spectrum cephalosporin or carbape nem would be appropriate initial treatment options in this patient who has complicated acute pyelonephritis. Uri- Item 20 Answer: C Educational Objective: Treat a patient with trauma- tr associated clostridial necrotizing skin and soft tissue nary tract infections in men, pregnant women, and per- infection. sons with foreign bodies (e.g., indwelling catheters, calculi). kidney disease, immunocompromise, obstruction, urinary This patient has Clostridium perfringens-associated necro- retention from neurologic disorders, health care-associated tizing fasciitis and myonecrosis and should receive antibiotic infections, or recent antibiotic use are considered to be treatment with penicillin and clindamycin (Option C); this complicated. This patient requires hospitalization because combination is recommended because some strains are resis- of potential hemodynamic instability. inability to toler- tant to clindamycin. Management of necrotizing fasciitis and ate oral medication. and concern for pathogen resistance myonecrosis secondary to C. perfringens includes prompt because of recent antimicrobial therapies. Urine and blood surgical debridement, intensive supportive care, and antibiot cultures should be performed as well. A detailed antibiotic ics. Clostridial myonecrosis is considered spontaneous (non- allergy history regarding possible reactions to penicillin is traumatic) or traumatic. Traumatic gas gangrene is associated required to determine the patient has no clear contraindi- with various conditions, including gunshot wounds, knife cation to these B-lactam medications and serves to avoid wounds, intramuscular injections, and skin-popping with the use of other potentially less effective and more costly heroin. The incubation period for infection can be as short as antimicrobial therapies. 6 hours with resultant sudden onset of tenderness. skin dis The monobactam aztreonam (Option A) is safe to pre coloration, systemic toxicity, and bullae formation. Imaging scribe in persons with a known or suspected severe allergr can demonstrate gas in the soft tissues. Identiflcation of C. to B-lactam antibiotics. However, this drug is unnecessary perfringens in soft tissue and blood can confirm the diagnosis. in a patient who reports having taken cephalosporin medi- In addition to surgical management, ceftazidime plus cations without a problem. doxycycline (Option A) is recommended for V uulnificr-rs- Empiric intravenous fluoroquinolones such as cip, associated severe necrotizing skin and soft tissue infections. rofloxacin and levofloxacin (Option C, D) are not reconl- Infection usually occurs in immunocompromised patients mended as initial treatment in hospitalized patients with (particularly with liver disease) after consumption of raw

Intravenous antimicrobial therapy with ceftriaxone (Option B) or another broad-spectrum cephalosporin or carbape nem would be appropriate initial treatment options in this patient who has complicated acute pyelonephritis. Uri- Item 20 Answer: C Educational Objective: Treat a patient with trauma- tr associated clostridial necrotizing skin and soft tissue nary tract infections in men, pregnant women, and per- infection. sons with foreign bodies (e.g., indwelling catheters, calculi). kidney disease, immunocompromise, obstruction, urinary This patient has Clostridium perfringens-associated necro- retention from neurologic disorders, health care-associated tizing fasciitis and myonecrosis and should receive antibiotic infections, or recent antibiotic use are considered to be treatment with penicillin and clindamycin (Option C); this complicated. This patient requires hospitalization because combination is recommended because some strains are resis- of potential hemodynamic instability. inability to toler- tant to clindamycin. Management of necrotizing fasciitis and ate oral medication. and concern for pathogen resistance myonecrosis secondary to C. perfringens includes prompt because of recent antimicrobial therapies. Urine and blood surgical debridement, intensive supportive care, and antibiot cultures should be performed as well. A detailed antibiotic ics. Clostridial myonecrosis is considered spontaneous (non- allergy history regarding possible reactions to penicillin is traumatic) or traumatic. Traumatic gas gangrene is associated required to determine the patient has no clear contraindi- with various conditions, including gunshot wounds, knife cation to these B-lactam medications and serves to avoid wounds, intramuscular injections, and skin-popping with the use of other potentially less effective and more costly heroin. The incubation period for infection can be as short as antimicrobial therapies. 6 hours with resultant sudden onset of tenderness. skin dis The monobactam aztreonam (Option A) is safe to pre coloration, systemic toxicity, and bullae formation. Imaging scribe in persons with a known or suspected severe allergr can demonstrate gas in the soft tissues. Identiflcation of C. to B-lactam antibiotics. However, this drug is unnecessary perfringens in soft tissue and blood can confirm the diagnosis. in a patient who reports having taken cephalosporin medi- In addition to surgical management, ceftazidime plus cations without a problem. doxycycline (Option A) is recommended for V uulnificr-rs- Empiric intravenous fluoroquinolones such as cip, associated severe necrotizing skin and soft tissue infections. rofloxacin and levofloxacin (Option C, D) are not reconl- Infection usually occurs in immunocompromised patients mended as initial treatment in hospitalized patients with (particularly with liver disease) after consumption of raw 148

Answers and Critiques l[ shellfish, such as oysters, or skin trauma incurred in warm recommend initiating three-drug ART without waiting for E 5s2 waters. such as the Gulf of Mexico, or brackish water. genotyping results, especially if no barriers prevent immedi_ c0NT' Ciprofloxacin plus (Option doxycycline B) is the anti- ate initiation. Updated guidelines have added select two_drug biotic regimen recommencied for Aeromonas hydrophila_ ART as a potential option for initial treatment of HIV infec- associated necrotizing skin and soft tissue inf'ections. tion; however, this should only be considered for individuals Lacerations and puncture wounds sustained in aquatic with HIV RNA less than 500,000 copies/ml, no hepatitis B envinlnrnents, including fresh water and brackish water, co infection, and available HIV reverse transcriptase geno- particularly during warmer weather montl-rs, can result in typic resistance testing results. With immediate or rapid start, rnound infection. Aerornonas infectior-rs of' the skin. soft when genotype data are unavailable, a three-drug ART regi tissue, and blood stream are more likely to occur in patients men is recommended. with underlying immunocompromising conditions such as The fourth generation HIV-tl2 antigen/antibody com- cirrhosis and cancer. bination immunoassay followed by a conflrmatory antibody Pending culture results. empiric antibiotic treatntent differentiation assay is the recommended two-step screen- tt fbr necrotizing fasciitis consists of vancomycin, daptomycin, c, ing test. Western blot testing for HIV is no longer performed J or linezolid plus piperacillin tazobactam; a carbapenem; as part of the laboratory protocol for diagnosing HIV infec- ET *, ceftriaxone plus metronidazole; or a fluoroquinolone plus tion because of problems with sensitivity in acute infection, L (J metronidazole. When culture results are available, how,ever. problems with interpretation of indeterminate results, and 'E antibiotic coverage should be targeted to the specific patho- wider availability of quantitative assays with faster turn- E IE gen(s). Current therapy (Option D) is too broad to continue around time (Option C). The current protocol demonstrates ta L for C. perfringens infection. an enhanced ability to detect acute HIV infection. lrt 3 vt Laboratory testing clearly shows that this patient has I(EY POIlIT E HIV-1 infection. Repeating HIV testing will not provide addi- o Clostndium perfringens-associated necrotizing fasciitis tional information for management and would increase costs and myonecrosis are treated with penicillin and clin- and delay treatment initiation unnecessarily (Option D). damycin. t(EY POtl{TS Bibliography . A fourth generation HIV-II2 antigen/antibody combi- Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of nation immunoassay test followed by a confirmatory America. Practice guidelines for the diagnosis and management of skin antibody differentiation assay is the recommended and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:etO SZ. [pl,ttO:24973422] doi:10.1093/ two-step screening test for HIV infection. cid/ciu444 . All persons with HIV infection should begin antiret roviral therapy as soon as they are ready, regardless of Item 21 Answer: A CD4 cell count. Educational Objective: Manage newly diagnosed HIV infection. Bibliography Panel on Antiretroviral Guidelines fbr Adults and Adolescents. Guidelines Antiretroviral therapy (ART) should be initiated immediately lor the use of antiretroviral agents in adults and adolescents with HIV. (Option A). A11 persons with HIV infection should begin Department of Health and Human Services. Available at http://www. aidsinfo.nih. gov/ContentFiles /AdultandAdolescentGL.pdf. Accessed ART as soon as they are ready, regardless of CD4 cell count. July 3, 2020. A large prospective, randomized clinical trial has resolved controversy over whether to start ART in asymptomatic patients with normal CD4 cell counts, demonstrating clear llem 22 clinical beneflt. Waiting for the CD4 cell count to drop below 350/pL was shown to put patients at risk for harm from Answer: C Educational Objective: Treat acute prostatitis in an tr older man. AIDS and non-AlDS-related complications (Option B). HIV treatment guidelines recommend immediate ARI initiation The most appropriate management of this patient is intrave- (either the same day as or within 2 weeks of diagnosis) if no nous ceftriaxone (Option C). Acute fevet urinary urgenc),', medical contraindications (concomitant opporlunistic infec frequency, dysuria, and pelvic discomfort are typical pre- tion in which immediate ART may be harmful) or structural senting symptoms of acute bacterial prostatitis. Second- barriers (staffing and linkage to care service availability) pre- ary bacteremia occurs in about 25% of patients with acute vent doing so. The World Health Organization also endorses prostatitis and is the most common cause of bacterentia in ART initiation within 7 days of new diagnosis (including older men. Gram negative uropathogens account fbr about same day), citing improved viral suppression. Transmitted B0'2, of infections, two thirds of which are Escherichia coli: drug resistance mutations have been a concern, and standard Proteus, Enterobacter, Serratia, Klebsiello, and sonletimes practice was to initiate ART only after genotyping data were Pseudomonos and enterococcal species compose most of available. However, this is changing as the rate of transmitted the other pathogens. Although pyuria may be present for drug resistance mutations continues to fall. Many experts reasons other than infection, its absence strongly indicates

l[ shellfish, such as oysters, or skin trauma incurred in warm recommend initiating three-drug ART without waiting for E 5s2 waters. such as the Gulf of Mexico, or brackish water. genotyping results, especially if no barriers prevent immedi_ c0NT' Ciprofloxacin plus (Option doxycycline B) is the anti- ate initiation. Updated guidelines have added select two_drug biotic regimen recommencied for Aeromonas hydrophila_ ART as a potential option for initial treatment of HIV infec- associated necrotizing skin and soft tissue inf'ections. tion; however, this should only be considered for individuals Lacerations and puncture wounds sustained in aquatic with HIV RNA less than 500,000 copies/ml, no hepatitis B envinlnrnents, including fresh water and brackish water, co infection, and available HIV reverse transcriptase geno- particularly during warmer weather montl-rs, can result in typic resistance testing results. With immediate or rapid start, rnound infection. Aerornonas infectior-rs of' the skin. soft when genotype data are unavailable, a three-drug ART regi tissue, and blood stream are more likely to occur in patients men is recommended. with underlying immunocompromising conditions such as The fourth generation HIV-tl2 antigen/antibody com- cirrhosis and cancer. bination immunoassay followed by a conflrmatory antibody Pending culture results. empiric antibiotic treatntent differentiation assay is the recommended two-step screen- tt fbr necrotizing fasciitis consists of vancomycin, daptomycin, c, ing test. Western blot testing for HIV is no longer performed J or linezolid plus piperacillin tazobactam; a carbapenem; as part of the laboratory protocol for diagnosing HIV infec- ET *, ceftriaxone plus metronidazole; or a fluoroquinolone plus tion because of problems with sensitivity in acute infection, L (J metronidazole. When culture results are available, how,ever. problems with interpretation of indeterminate results, and 'E antibiotic coverage should be targeted to the specific patho- wider availability of quantitative assays with faster turn- E IE gen(s). Current therapy (Option D) is too broad to continue around time (Option C). The current protocol demonstrates ta L for C. perfringens infection. an enhanced ability to detect acute HIV infection. lrt 3 vt Laboratory testing clearly shows that this patient has I(EY POIlIT E HIV-1 infection. Repeating HIV testing will not provide addi- o Clostndium perfringens-associated necrotizing fasciitis tional information for management and would increase costs and myonecrosis are treated with penicillin and clin- and delay treatment initiation unnecessarily (Option D). damycin. t(EY POtl{TS Bibliography . A fourth generation HIV-II2 antigen/antibody combi- Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of nation immunoassay test followed by a confirmatory America. Practice guidelines for the diagnosis and management of skin antibody differentiation assay is the recommended and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:etO SZ. [pl,ttO:24973422] doi:10.1093/ two-step screening test for HIV infection. cid/ciu444 . All persons with HIV infection should begin antiret roviral therapy as soon as they are ready, regardless of Item 21 Answer: A CD4 cell count. Educational Objective: Manage newly diagnosed HIV infection. Bibliography Panel on Antiretroviral Guidelines fbr Adults and Adolescents. Guidelines Antiretroviral therapy (ART) should be initiated immediately lor the use of antiretroviral agents in adults and adolescents with HIV. (Option A). A11 persons with HIV infection should begin Department of Health and Human Services. Available at http://www. aidsinfo.nih. gov/ContentFiles /AdultandAdolescentGL.pdf. Accessed ART as soon as they are ready, regardless of CD4 cell count. July 3, 2020. A large prospective, randomized clinical trial has resolved controversy over whether to start ART in asymptomatic patients with normal CD4 cell counts, demonstrating clear llem 22 clinical beneflt. Waiting for the CD4 cell count to drop below 350/pL was shown to put patients at risk for harm from Answer: C Educational Objective: Treat acute prostatitis in an tr older man. AIDS and non-AlDS-related complications (Option B). HIV treatment guidelines recommend immediate ARI initiation The most appropriate management of this patient is intrave- (either the same day as or within 2 weeks of diagnosis) if no nous ceftriaxone (Option C). Acute fevet urinary urgenc),', medical contraindications (concomitant opporlunistic infec frequency, dysuria, and pelvic discomfort are typical pre- tion in which immediate ART may be harmful) or structural senting symptoms of acute bacterial prostatitis. Second- barriers (staffing and linkage to care service availability) pre- ary bacteremia occurs in about 25% of patients with acute vent doing so. The World Health Organization also endorses prostatitis and is the most common cause of bacterentia in ART initiation within 7 days of new diagnosis (including older men. Gram negative uropathogens account fbr about same day), citing improved viral suppression. Transmitted B0'2, of infections, two thirds of which are Escherichia coli: drug resistance mutations have been a concern, and standard Proteus, Enterobacter, Serratia, Klebsiello, and sonletimes practice was to initiate ART only after genotyping data were Pseudomonos and enterococcal species compose most of available. However, this is changing as the rate of transmitted the other pathogens. Although pyuria may be present for drug resistance mutations continues to fall. Many experts reasons other than infection, its absence strongly indicates 149

Answers and Critiques FFI no infection. t-lospitalized patients and those with severe regimen (isoniazid, rifampin, pyrazinamide, ethambutol) 1ll in1".tion require ltlood cultures. Reasonable initial antibiotic (Option C). Although a tuberculin skin test has not been c0NI .h,,i.es fbr severely ill patients with acute prostatitis include performed and the flnal sputum culture is pending, the an intrar,'enotts broacl spectrunr parenteral antibiotic. such as patient has a signiflcant personal history that increases an cxtende<i spectrum penicillin or cephalosporin. rvith tlte her risk of tuberculosis; she works in a high-risk setting possible addition of' an irnrinoglycoside. (prison). She has several key symptoms and signs of pul- Intravettotts ampicillin (Option A) might be considered monary tuberculosis, including weight loss, fever, night it' the urine Gram stain clenlonstrated gri"lll1 positive cocci sweats, productive cough, malaise, and fatigue; the chest in chains suggesting an etlterococcal irlf'ectiou. However, radiograph is compatible with active tuberculosis, and she ampicillin resistant etlterococci do exist. and anlpicillin has a classic sputum acid fast bacilli (AFB) stain. When a wclulcl t-tclt be efl'ective ag:rinst the more cofillrloll causes of' sputum smear result is positive for AFB, nucleic acid ampli- acute bacterial prosttititis in olcler metl. flcation testing (NAAT) is highty recommended to verify D For sttspected Psettdontoticls rieruginoso inf'ectiot-t. the organism. The positive predictive value of a NAAT on a J vt cef'epirne u,ottlcl be approlrriate; l.tulvever. tl-ris patient smear-positive sputum sample is 95%. When active tuber- cloes not have suspected P oerugitrosci inf'ection. lrmpiric culosis is verified, in vitro susceptibility testing of the initial = .D - UI treatment with doxycycline or a nlacrolicle and testing isolate should be done for the flrst-line agents (isoniazid, o, ) fbr serually tratismittecl pathogens sttcl.t ;ts Cltlumgdia rifampin, pyrazinamide, and ethambutol) which should CL trcic'honiotis would be inclicitted ir-r youllger tnetl w'itl-t be initiated as soon as possible to prevent further disease a-l rl lcute prostatte inf'ections, as r.toulcl Neisseria gonor progression and transmission. -t -D rhoeae, but in older patients. these inf'ections would be Clarithromycin and ethambutol (Option A) is the pre It -a

FFI no infection. t-lospitalized patients and those with severe regimen (isoniazid, rifampin, pyrazinamide, ethambutol) 1ll in1".tion require ltlood cultures. Reasonable initial antibiotic (Option C). Although a tuberculin skin test has not been c0NI .h,,i.es fbr severely ill patients with acute prostatitis include performed and the flnal sputum culture is pending, the an intrar,'enotts broacl spectrunr parenteral antibiotic. such as patient has a signiflcant personal history that increases an cxtende<i spectrum penicillin or cephalosporin. rvith tlte her risk of tuberculosis; she works in a high-risk setting possible addition of' an irnrinoglycoside. (prison). She has several key symptoms and signs of pul- Intravettotts ampicillin (Option A) might be considered monary tuberculosis, including weight loss, fever, night it' the urine Gram stain clenlonstrated gri"lll1 positive cocci sweats, productive cough, malaise, and fatigue; the chest in chains suggesting an etlterococcal irlf'ectiou. However, radiograph is compatible with active tuberculosis, and she ampicillin resistant etlterococci do exist. and anlpicillin has a classic sputum acid fast bacilli (AFB) stain. When a wclulcl t-tclt be efl'ective ag:rinst the more cofillrloll causes of' sputum smear result is positive for AFB, nucleic acid ampli- acute bacterial prosttititis in olcler metl. flcation testing (NAAT) is highty recommended to verify D For sttspected Psettdontoticls rieruginoso inf'ectiot-t. the organism. The positive predictive value of a NAAT on a J vt cef'epirne u,ottlcl be approlrriate; l.tulvever. tl-ris patient smear-positive sputum sample is 95%. When active tuber- cloes not have suspected P oerugitrosci inf'ection. lrmpiric culosis is verified, in vitro susceptibility testing of the initial = .D - UI treatment with doxycycline or a nlacrolicle and testing isolate should be done for the flrst-line agents (isoniazid, o, ) fbr serually tratismittecl pathogens sttcl.t ;ts Cltlumgdia rifampin, pyrazinamide, and ethambutol) which should CL trcic'honiotis would be inclicitted ir-r youllger tnetl w'itl-t be initiated as soon as possible to prevent further disease a-l rl lcute prostatte inf'ections, as r.toulcl Neisseria gonor progression and transmission. -t -D rhoeae, but in older patients. these inf'ections would be Clarithromycin and ethambutol (Option A) is the pre It -a E (D Llrlconlmon. so cefepime and doxycycline (Option B) are ferred regimen for Mycobacterium auium complex, not la not itrdicatecl. Mycobacterium tuberculosis. This would be insufficient l.luoroquinokxtes (such as levo{loxacin) (Option D) treatment for M. tuberculosis infection. should be avoicled as initial antibiotic therapy in patients Although it is one of the antimicrobials used to treat with severe inf'ection \ /arrilnting hospitalization when krcal tuberculosis, isoniazid alone (Option B) is not indicated resistance rates exceecl 10'},,, or when other patient specific for active tuberculosis. It is only indicated as monotherapy resistance risk fiictors erist. sttch as recent hospitalization for treatment of latent tuberculosis. Isoniazid monotherapy or fluoroquirrolone use, as in this patient. Assuming tlre in active tuberculosis could promote the development of crusative bacterial pathogen has been determined to be isoniazid resistance. susceptible to these antibiotics and clinical intproventent In the United States, the incidence of isoniazid resis- is lcl-rieved. transition to oral levofloxacin or ciprofloxacin tance ranges from 4.7o1, to 14.4%; global resistance rates are would be approlrriate. higher. The regimen of rifampin, ethambutol, pyrazinamide, and levofloxacin (Option D) is a safe and reasonable option KEY POIt{T5 for patients with proven isoniazid resistance. At this time, . Reasonable initial antibiotic choices for severely ill the patient has no indication of isoniazid resistance, and iso- patients with acute prostatitis include an intravenous niazid, rifampin, pyrazinamide, and ethambutol is guideline broad-spectrum parenteral antibiotic, such as an recommended as flrst-line therapy. extended-spectrum penicillin or cephalosporin, with rEY POIT{T or without the addition of an aminoglycoside. o Fluoroquinolones should not be used as initial antibi- . When active tuberculosis is verified, in vitro suscepti- bihty testing of the initial isolate should be done for the otic therapy in patients with severe infection that fi rst-line agents (isoniazid, rifampin, pyrazinamide, warrants hospitalization when local resistance rates and ethambutol), which should be started as soon as exceed 10u/,, or when other patient-specific resistance possible. risk factors (e.g., recent hospitalization or fluoro quinolone use) exist. Bibliography Lewinsohn DM, Leonard MK, LoBue PA. et al. Official American Thoracic Bibliography Society/lnfectious Diseases Society of America/Centers for Disease Gill BC, Shoskes DA. Bacterial prostatitis. Curr Opin Infect Dis. 2016;29 Control and Prevention clinical practice guidelines: diagnosis of tubercu- 86 91. [PMID: 26555038] doi:10.1097/QCO.0000000000000222 losis in adults and children. Clin Infect Dis. 2017;64:111 ll5. [PMIO, zaoszg 0z) doi: 10. 1093 /cid/ciw77B

E (D Llrlconlmon. so cefepime and doxycycline (Option B) are ferred regimen for Mycobacterium auium complex, not la not itrdicatecl. Mycobacterium tuberculosis. This would be insufficient l.luoroquinokxtes (such as levo{loxacin) (Option D) treatment for M. tuberculosis infection. should be avoicled as initial antibiotic therapy in patients Although it is one of the antimicrobials used to treat with severe inf'ection \ /arrilnting hospitalization when krcal tuberculosis, isoniazid alone (Option B) is not indicated resistance rates exceecl 10'},,, or when other patient specific for active tuberculosis. It is only indicated as monotherapy resistance risk fiictors erist. sttch as recent hospitalization for treatment of latent tuberculosis. Isoniazid monotherapy or fluoroquirrolone use, as in this patient. Assuming tlre in active tuberculosis could promote the development of crusative bacterial pathogen has been determined to be isoniazid resistance. susceptible to these antibiotics and clinical intproventent In the United States, the incidence of isoniazid resis- is lcl-rieved. transition to oral levofloxacin or ciprofloxacin tance ranges from 4.7o1, to 14.4%; global resistance rates are would be approlrriate. higher. The regimen of rifampin, ethambutol, pyrazinamide, and levofloxacin (Option D) is a safe and reasonable option KEY POIt{T5 for patients with proven isoniazid resistance. At this time, . Reasonable initial antibiotic choices for severely ill the patient has no indication of isoniazid resistance, and iso- patients with acute prostatitis include an intravenous niazid, rifampin, pyrazinamide, and ethambutol is guideline broad-spectrum parenteral antibiotic, such as an recommended as flrst-line therapy. extended-spectrum penicillin or cephalosporin, with rEY POIT{T or without the addition of an aminoglycoside. o Fluoroquinolones should not be used as initial antibi- . When active tuberculosis is verified, in vitro suscepti- bihty testing of the initial isolate should be done for the otic therapy in patients with severe infection that fi rst-line agents (isoniazid, rifampin, pyrazinamide, warrants hospitalization when local resistance rates and ethambutol), which should be started as soon as exceed 10u/,, or when other patient-specific resistance possible. risk factors (e.g., recent hospitalization or fluoro quinolone use) exist. Bibliography Lewinsohn DM, Leonard MK, LoBue PA. et al. Official American Thoracic Bibliography Society/lnfectious Diseases Society of America/Centers for Disease Gill BC, Shoskes DA. Bacterial prostatitis. Curr Opin Infect Dis. 2016;29 Control and Prevention clinical practice guidelines: diagnosis of tubercu- 86 91. [PMID: 26555038] doi:10.1097/QCO.0000000000000222 losis in adults and children. Clin Infect Dis. 2017;64:111 ll5. [PMIO, zaoszg 0z) doi: 10. 1093 /cid/ciw77B Item 23 Answer: C Item 24 Answer: E Educational Objective: Treat pulmonary tuberculosis Ed ucationa I Objective: Identiff appropriate vaccines infection. for patients with HIV infection. The patient has active pulmonary tuberculosis requir- This patient has no contraindications to routinely adminis- ing treatment with the four drug tuberculosis treatment tered vaccines (Option E). Live vaccines, including varicella,

Item 23 Answer: C Item 24 Answer: E Educational Objective: Treat pulmonary tuberculosis Ed ucationa I Objective: Identiff appropriate vaccines infection. for patients with HIV infection. The patient has active pulmonary tuberculosis requir- This patient has no contraindications to routinely adminis- ing treatment with the four drug tuberculosis treatment tered vaccines (Option E). Live vaccines, including varicella, 150

Answers and Critiques varicella zoster, measles-mumps-rubella, and influenza are Item 25 not recommended for patients who are severely immuno_ Answer: B Ed ucatio na I Obiective: Prevent anthrax following compromised. Contraindications to live vaccines include potential exposure. persons with HIV with CD4 cell count <2OOlStL; pregnancy or probable pregnancy within 4 weeks; immunosuppres- Doxycycline and anthrax vaccination are the most appropriate sant therapy, including high-dose glucocorticoids; leukemia, management options for this patient (Option B). Although lymphoma, or other bone marrow and lymphatic system he is asymptomatic, it should be assumed that he was inten- malignancies; cellular immunodeflciency; solid organ trans tionally exposed to anthrax spores. Postexposure prophylactic plant recipient; and recent hematopoietic stem cell trans- antibiotic therapy must begin immediately after any local plantation. or systemic infection has been excluded. Ciprofloxacin and The live-attenuated influenza vaccine is contraindi- doxycycline are the preferred flrst-line agents. Doxycycline is cated in patients with HIV inf'ection regardless of CD4 cell the safer choice in this patient, who has a history of tendon count, but the inactivated vaccine can be given (Option repair, because of the association of ciprofloxacin and other UI (u B). Numerous other immunizations are recommended fluoroquinolone options (levofloxacin and moxifloxacin) with for all persons with HIV including COVID 19, 13-valent the risk of tendinopathy. Because antibiotics are only active ET y a-

varicella zoster, measles-mumps-rubella, and influenza are Item 25 not recommended for patients who are severely immuno_ Answer: B Ed ucatio na I Obiective: Prevent anthrax following compromised. Contraindications to live vaccines include potential exposure. persons with HIV with CD4 cell count <2OOlStL; pregnancy or probable pregnancy within 4 weeks; immunosuppres- Doxycycline and anthrax vaccination are the most appropriate sant therapy, including high-dose glucocorticoids; leukemia, management options for this patient (Option B). Although lymphoma, or other bone marrow and lymphatic system he is asymptomatic, it should be assumed that he was inten- malignancies; cellular immunodeflciency; solid organ trans tionally exposed to anthrax spores. Postexposure prophylactic plant recipient; and recent hematopoietic stem cell trans- antibiotic therapy must begin immediately after any local plantation. or systemic infection has been excluded. Ciprofloxacin and The live-attenuated influenza vaccine is contraindi- doxycycline are the preferred flrst-line agents. Doxycycline is cated in patients with HIV inf'ection regardless of CD4 cell the safer choice in this patient, who has a history of tendon count, but the inactivated vaccine can be given (Option repair, because of the association of ciprofloxacin and other UI (u B). Numerous other immunizations are recommended fluoroquinolone options (levofloxacin and moxifloxacin) with for all persons with HIV including COVID 19, 13-valent the risk of tendinopathy. Because antibiotics are only active ET y a- pneumococcal conjugate, and 23-valent pneumococcal against vegetative bacilli, they are administered for 60 days, a- L rJ polysaccharide vaccines. Patients who are not already helping to ensure that late germination of spores lying dor !ts immune or infected with hepatitis B virus should receive mant in the lungs and macrophages does not evolve into aq - the hepatitis B vaccine series. Tetanus diphtheria active disease. Postexposure protocols for anthrax include ttt L pertussis, hepatitis A, and human papillomavirus (HPV) immunization along with antibiotics. The approved vaccine C'

pneumococcal conjugate, and 23-valent pneumococcal against vegetative bacilli, they are administered for 60 days, a- L rJ polysaccharide vaccines. Patients who are not already helping to ensure that late germination of spores lying dor !ts immune or infected with hepatitis B virus should receive mant in the lungs and macrophages does not evolve into aq - the hepatitis B vaccine series. Tetanus diphtheria active disease. Postexposure protocols for anthrax include ttt L pertussis, hepatitis A, and human papillomavirus (HPV) immunization along with antibiotics. The approved vaccine C' vaccinations are indicated as for the general popula should be given within 10 days of exposure and is adminis- ttl = F

vaccinations are indicated as for the general popula should be given within 10 days of exposure and is adminis- ttl = F tion (Option A). The Advisory Committee on Immuni tered subcutaneously on weeks O,2, and 4. zation Practices (ACtp) has expanded the age indications When given early in combination with antibacterial for HPV vaccination to 45 years, recommending that therapy, the toxin-neutralizing human monoclonal anti- the decision to vaccinate between ages 26 and 45 years bodies raxibacumab (Option A) and obiltoxaximab are ben- be determined through shared decision making with eflcial in the treatment of systemic anthrax, as is anthrax patients. The ACIP recommends that all persons with immune giobulin. They are only intended for use in post HIV infection be vaccinated for meningococcal disease exposure prophylaxis when alternative preventive therapies with the quadrivalent meningococcal vaccine, including are unavailable or inappropriate. boosters every 5 years. Initial multidrug antimicrobial therapy with a fluor- For prevention of varicella-zoster, live-attenuated and oquinolone or doxycycline, a second active agent (e.g., pen- recombinant vaccines are available; the inactivated recombi- icillin, meropenem, vancomycin), and a protein synthesis nant vaccine is preferred and recommended for patients aged inhibitor (e.g., linezolid, clindamycin) (Option C) is standard 50 years and older, even if the patient previously received the treatment of anthrax with systemic manifestations. It should live varicella-zoster vaccine. For patients without immu- also be initially prescribed for patients with nonsevere cuta nity, selected live vaccines such as the measles-mumps- neous disease when intentional release of anthrax spores is rubella and varicella vaccines can be given to patients with suspected. HIV infection as long as the CD4 cell count is greater than Person-to person transmission of anthrax does not 200lytL (Option C, D). occur, so it is unnecessary for the patient to be isolated (Option D). TEY POIT{TS Although he had no direct contact with the ill cowork- o Selected live vaccines, including the varicella and ers, concern for a common covert anthrax exposure is an measles-mumps-rubella vaccines, are safe to admin- indication for postexposure prophylaxis. Therefore, clinical ister to nonimmune persons with HIV infection observation alone would be inappropriate (Option E). whose CD4 cell count has consistently been greater r(EY POtf{TS than 200/pL. o The live influenza vaccine is contraindicated in o In patients potentially exposed to anthrax spores and immunocompromised patients and those with HIV without local or systemic infection, prophylaxis with doxycycline or ciprofloxacin plus anthrax immuniza- regardless of CD4 cell count. tion should be provided. Bibliography o Initial multidrug antimicrobial therapy with a fluor- Panel on Opportunistic Infections in HIV Infected Adults and Adolescents. oquinolone or doxycycline, a second active agent Guidelines for the prevention and treatment of opportunistic infec (e.g., penicillin, meropenem, vancomycin), and a pro- tions in HIV infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention. the National Institutes tein synthesis inhibitor (e.g., linezolid, clindamycin) of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated April 17, 2020. Available at https://aid- is standard treatment of anthrax with systemic man sinfo. nih. gov/guidelines /html/4 /adult-and adolescent-opportunistic ifestations. infection/0.

tion (Option A). The Advisory Committee on Immuni tered subcutaneously on weeks O,2, and 4. zation Practices (ACtp) has expanded the age indications When given early in combination with antibacterial for HPV vaccination to 45 years, recommending that therapy, the toxin-neutralizing human monoclonal anti- the decision to vaccinate between ages 26 and 45 years bodies raxibacumab (Option A) and obiltoxaximab are ben- be determined through shared decision making with eflcial in the treatment of systemic anthrax, as is anthrax patients. The ACIP recommends that all persons with immune giobulin. They are only intended for use in post HIV infection be vaccinated for meningococcal disease exposure prophylaxis when alternative preventive therapies with the quadrivalent meningococcal vaccine, including are unavailable or inappropriate. boosters every 5 years. Initial multidrug antimicrobial therapy with a fluor- For prevention of varicella-zoster, live-attenuated and oquinolone or doxycycline, a second active agent (e.g., pen- recombinant vaccines are available; the inactivated recombi- icillin, meropenem, vancomycin), and a protein synthesis nant vaccine is preferred and recommended for patients aged inhibitor (e.g., linezolid, clindamycin) (Option C) is standard 50 years and older, even if the patient previously received the treatment of anthrax with systemic manifestations. It should live varicella-zoster vaccine. For patients without immu- also be initially prescribed for patients with nonsevere cuta nity, selected live vaccines such as the measles-mumps- neous disease when intentional release of anthrax spores is rubella and varicella vaccines can be given to patients with suspected. HIV infection as long as the CD4 cell count is greater than Person-to person transmission of anthrax does not 200lytL (Option C, D). occur, so it is unnecessary for the patient to be isolated (Option D). TEY POIT{TS Although he had no direct contact with the ill cowork- o Selected live vaccines, including the varicella and ers, concern for a common covert anthrax exposure is an measles-mumps-rubella vaccines, are safe to admin- indication for postexposure prophylaxis. Therefore, clinical ister to nonimmune persons with HIV infection observation alone would be inappropriate (Option E). whose CD4 cell count has consistently been greater r(EY POtf{TS than 200/pL. o The live influenza vaccine is contraindicated in o In patients potentially exposed to anthrax spores and immunocompromised patients and those with HIV without local or systemic infection, prophylaxis with doxycycline or ciprofloxacin plus anthrax immuniza- regardless of CD4 cell count. tion should be provided. Bibliography o Initial multidrug antimicrobial therapy with a fluor- Panel on Opportunistic Infections in HIV Infected Adults and Adolescents. oquinolone or doxycycline, a second active agent Guidelines for the prevention and treatment of opportunistic infec (e.g., penicillin, meropenem, vancomycin), and a pro- tions in HIV infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention. the National Institutes tein synthesis inhibitor (e.g., linezolid, clindamycin) of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated April 17, 2020. Available at https://aid- is standard treatment of anthrax with systemic man sinfo. nih. gov/guidelines /html/4 /adult-and adolescent-opportunistic ifestations. infection/0. 151

Answers and Critiques Bibliography f,EY POII{I5 Hendricks KA, Wright ME, Shadomy SV et al; Workgroup on Anthrax o Cytomegalovirus infection remains a risk in solid Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in organ transplant recipients after prophylaxis discon- Emerg Infect Dis. 2014;20. [PMID: 24447897] doi:10'3201/ ^Arttt. eid2002.130687 tinuation if they were seronegative for the virus and received an organ from a seropositive donor. . Cytomegalovirus infection can cause retinitis, pneu- Item 25 Answer: A monitis, hepatitis, bone marrow suppression, colitis, Ed ucational Objective : Diagnose c5rtomegalovirus esophagitis, and adrenalitis in immunocompromised infection in a patient who has undergone solid organ persons. transplantation. Cytomegalovirus is the most likely infection present in this Bibliography D patient (Option A). Several factors influence determining a Fishman JA. Infection in organ transplantation. Am J Transplant. 2Ol7;17 J 856 - 879. [pl,t tO, ZA]]^Z g q q) doi: 10. 1111 /ajt. 14208 UI causative pathogen in an organ transplant recipient. Know E ing the timeline of common posttransplant infections is { (D UI helpful, as is donor and recipient serostatus for infections Item 27 Answer: D o, J like cytomegalovirus. The degree of risk and probability Educationa I Objective: Diagnose common variable TL rl of an infection can also be determined by the patient's immunodeflciency. - current prophylaxis. Because this patient was cytomegalo lt=. virus negative and the donor was seropositive, the patient Pneumococcal and tetanus antibodies should be measured E (D was at very high risk for cytomegalovirus infection and its before and after vaccination (Option D). This patient has had UI recurrent sinopulmonary infections and has low quantita- end-organ complications. He received 6 months of pro- phylaxis, which helped prevent early onset cytomegalovi- tive immunoglobulin levels, which suggests common variable rus infection and disease from the donor organ. However, immunodeflciency (CVID). Several diagnostic criteria have when prophylaxis is stopped and immunosuppression is been proposed for CVID, but all require documentation of ongoing, late-onset cytomegalovirus infection and disease low IgG levels, with variable presence of decreased IgA and is a risk. Cytomegalovirus infection can cause retinitis, IgM antibody, and demonstration of impaired antibody pro- pneumonitis, hepatitis, bone marrow suppression, coli- duction to antigenic stimulation. Antibody synthesis should tis, esophagitis, and adrenalitis in immunocompromised be assessed by measuring antibody levels before and after persons. Therefore, new-onset fever and malaise with lab- pneumococcal polysaccharide and tetanus vaccinations. CVID oratory evidence of cytopenia and liver enzyme elevation increases risk of upper and lower respiratory tract infections should prompt consideration for primary cytomegalovirus caused by encapsulated bacteia, Mycoplasma species, and infection. respiratory viruses. Chronic diarrhea with malabsorption Pneumocystis jirouecii infections, especially pneumo- suggests giardiasis or chronic norovirus infection. Addition- nia, are a concern in organ transplant recipients. However, ally, patients with CVID are at increased risk of autoimmune with the patient's ongoing trimethoprim-sulfamethoxazole disease, inflammatory bowel disease, granulomatous disease prophylaxis, the likelihood of Pneumocystis infection is very (noncaseating granulomas in the lymphoid or solid organs), low (Option B). bronchiectasis, and malignancy. Unlike many primary immu- Polyomaviruses (BK and JC) contribute to morbidity nodeflciencies, CVID is often diagnosed in adults rather than in immunosuppressed patients, including organ trans- during childhood. Diagnosing CVID is important because plant recipients (Option C, D). However, these infections immunoglobulin replacement therapy decreases the risk of tend to present 12 months or more after transplantation. subsequent infections. BK virus typically causes more localized complications Severe combined immunodeflciency (SCID) is an in kidney transplant recipients, especially tubulointer- inherited primary immunodeflciency involving humoral stitial nephritis and nephropathy. Similarly, syndromes and cellular immunity. Typical manifestations include caused by JC virus tend to be localized to the central chronic mucocutaneous candidiasis, recurrent, chronic nervous system. Progressive multifocal leukoenceph- diarrhea, and severe opportunistic infections such as alopathy is the most common presentation of JC virus Pneumocystis jirouecii. SCID is a pediatric disease, with infection; however, these infections are rare and are patients rarely surviving to adulthood; therefore, CD4 only seen in patients who have had more intense immu- T-cell subset measurement is not necessary in this patient nosuppression related to advancing age, other comor- (Option A). bidities, and frequent episodes of rejection. Patients Patients with CVID should receive appropriate present with focal neurologic deficits or seizures and immunizations with inactivated vaccines, recognizing have characteristic white matter changes on brain MRI. that the immunologic response is likely to be blunted. Polyomaviruses are unlikely to cause a syndrome like The measles vaccine is a live attenuated virus and is con- cytomegalovirus infection, including cytopenia and traindicated in patients with immunodeficiency, includ- Iiver enzyme elevation. ing CVID (Option B).

Bibliography f,EY POII{I5 Hendricks KA, Wright ME, Shadomy SV et al; Workgroup on Anthrax o Cytomegalovirus infection remains a risk in solid Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in organ transplant recipients after prophylaxis discon- Emerg Infect Dis. 2014;20. [PMID: 24447897] doi:10'3201/ ^Arttt. eid2002.130687 tinuation if they were seronegative for the virus and received an organ from a seropositive donor. . Cytomegalovirus infection can cause retinitis, pneu- Item 25 Answer: A monitis, hepatitis, bone marrow suppression, colitis, Ed ucational Objective : Diagnose c5rtomegalovirus esophagitis, and adrenalitis in immunocompromised infection in a patient who has undergone solid organ persons. transplantation. Cytomegalovirus is the most likely infection present in this Bibliography D patient (Option A). Several factors influence determining a Fishman JA. Infection in organ transplantation. Am J Transplant. 2Ol7;17 J 856 - 879. [pl,t tO, ZA]]^Z g q q) doi: 10. 1111 /ajt. 14208 UI causative pathogen in an organ transplant recipient. Know E ing the timeline of common posttransplant infections is { (D UI helpful, as is donor and recipient serostatus for infections Item 27 Answer: D o, J like cytomegalovirus. The degree of risk and probability Educationa I Objective: Diagnose common variable TL rl of an infection can also be determined by the patient's immunodeflciency. - current prophylaxis. Because this patient was cytomegalo lt=. virus negative and the donor was seropositive, the patient Pneumococcal and tetanus antibodies should be measured E (D was at very high risk for cytomegalovirus infection and its before and after vaccination (Option D). This patient has had UI recurrent sinopulmonary infections and has low quantita- end-organ complications. He received 6 months of pro- phylaxis, which helped prevent early onset cytomegalovi- tive immunoglobulin levels, which suggests common variable rus infection and disease from the donor organ. However, immunodeflciency (CVID). Several diagnostic criteria have when prophylaxis is stopped and immunosuppression is been proposed for CVID, but all require documentation of ongoing, late-onset cytomegalovirus infection and disease low IgG levels, with variable presence of decreased IgA and is a risk. Cytomegalovirus infection can cause retinitis, IgM antibody, and demonstration of impaired antibody pro- pneumonitis, hepatitis, bone marrow suppression, coli- duction to antigenic stimulation. Antibody synthesis should tis, esophagitis, and adrenalitis in immunocompromised be assessed by measuring antibody levels before and after persons. Therefore, new-onset fever and malaise with lab- pneumococcal polysaccharide and tetanus vaccinations. CVID oratory evidence of cytopenia and liver enzyme elevation increases risk of upper and lower respiratory tract infections should prompt consideration for primary cytomegalovirus caused by encapsulated bacteia, Mycoplasma species, and infection. respiratory viruses. Chronic diarrhea with malabsorption Pneumocystis jirouecii infections, especially pneumo- suggests giardiasis or chronic norovirus infection. Addition- nia, are a concern in organ transplant recipients. However, ally, patients with CVID are at increased risk of autoimmune with the patient's ongoing trimethoprim-sulfamethoxazole disease, inflammatory bowel disease, granulomatous disease prophylaxis, the likelihood of Pneumocystis infection is very (noncaseating granulomas in the lymphoid or solid organs), low (Option B). bronchiectasis, and malignancy. Unlike many primary immu- Polyomaviruses (BK and JC) contribute to morbidity nodeflciencies, CVID is often diagnosed in adults rather than in immunosuppressed patients, including organ trans- during childhood. Diagnosing CVID is important because plant recipients (Option C, D). However, these infections immunoglobulin replacement therapy decreases the risk of tend to present 12 months or more after transplantation. subsequent infections. BK virus typically causes more localized complications Severe combined immunodeflciency (SCID) is an in kidney transplant recipients, especially tubulointer- inherited primary immunodeflciency involving humoral stitial nephritis and nephropathy. Similarly, syndromes and cellular immunity. Typical manifestations include caused by JC virus tend to be localized to the central chronic mucocutaneous candidiasis, recurrent, chronic nervous system. Progressive multifocal leukoenceph- diarrhea, and severe opportunistic infections such as alopathy is the most common presentation of JC virus Pneumocystis jirouecii. SCID is a pediatric disease, with infection; however, these infections are rare and are patients rarely surviving to adulthood; therefore, CD4 only seen in patients who have had more intense immu- T-cell subset measurement is not necessary in this patient nosuppression related to advancing age, other comor- (Option A). bidities, and frequent episodes of rejection. Patients Patients with CVID should receive appropriate present with focal neurologic deficits or seizures and immunizations with inactivated vaccines, recognizing have characteristic white matter changes on brain MRI. that the immunologic response is likely to be blunted. Polyomaviruses are unlikely to cause a syndrome like The measles vaccine is a live attenuated virus and is con- cytomegalovirus infection, including cytopenia and traindicated in patients with immunodeficiency, includ- Iiver enzyme elevation. ing CVID (Option B). 152

Answers and Critiques Measurement of IgG subsets would not provide useful Cefazolir-r (Option B) is an appropriate antibiotic if'the information in this setting when the total IgG level is low and isolate is determined to be methicillin-susceptible S. ourcus. would not change management in this patient (Option C). but it should not be used as entpiric therapy in this setting. Antibiotic therapy is indicated for active infections, but Vertebral osteomyelitis can be caused by gram-negative prophylaxis is not routinely recommended in patients with organisms. A broad-spectrum. gram,negative agent such as CVID because it can select for increasingly resistant organ- cefepime can be added to vancomycin (Option D) as empiric isms (Option E). Prophylaxis is recommended in patients therapy for vertebral osteomyelitis in patients with signs of with CD4 cell counts less than 2OOlltLorwith chronic gran- sepsis pending f'urther microbiologic data, but this patient ulomatous disease. has multiple blood cultures growing only gram-positive t(EY POll{TS organisms, so gram-negative coverage is unnecessary. . Common variable immunodeficiency increases the I(EY POI ilTS risk of upper and lower respiratory tract infections . StaphAlococcus aureus is the most likely pathogen in vt caused by encapsulated bactefia, Mycoplasma adults with vertebral osteomyelitis. C, d species, and respiratory viruses as well as chronic ET o In patients with vertebral osteomyelitis and positive F diarrhea caused by giardiasis or chronic norovirus blood cultures for a typical pathogen, bone biopsy is L rJ infection. generally not indicated. -t? o Common variable immunodeficiency can be diag- IE l,I nosed in persons with documented low IgG levels, Bibliography L (, impaired antibody production to pneumococcal or Berbari EFi, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of Ut tetanus vaccines, and variably decreased IgA and IgM America (IDSA) clinical practice guidelines for the diagnosis and treat- = E ment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015; antibody levels. 67 : e26 - 46. [PM I O, 26229122) doi : 1 0. 1 09 3 /c id I civ 482

Measurement of IgG subsets would not provide useful Cefazolir-r (Option B) is an appropriate antibiotic if'the information in this setting when the total IgG level is low and isolate is determined to be methicillin-susceptible S. ourcus. would not change management in this patient (Option C). but it should not be used as entpiric therapy in this setting. Antibiotic therapy is indicated for active infections, but Vertebral osteomyelitis can be caused by gram-negative prophylaxis is not routinely recommended in patients with organisms. A broad-spectrum. gram,negative agent such as CVID because it can select for increasingly resistant organ- cefepime can be added to vancomycin (Option D) as empiric isms (Option E). Prophylaxis is recommended in patients therapy for vertebral osteomyelitis in patients with signs of with CD4 cell counts less than 2OOlltLorwith chronic gran- sepsis pending f'urther microbiologic data, but this patient ulomatous disease. has multiple blood cultures growing only gram-positive t(EY POll{TS organisms, so gram-negative coverage is unnecessary. . Common variable immunodeficiency increases the I(EY POI ilTS risk of upper and lower respiratory tract infections . StaphAlococcus aureus is the most likely pathogen in vt caused by encapsulated bactefia, Mycoplasma adults with vertebral osteomyelitis. C, d species, and respiratory viruses as well as chronic ET o In patients with vertebral osteomyelitis and positive F diarrhea caused by giardiasis or chronic norovirus blood cultures for a typical pathogen, bone biopsy is L rJ infection. generally not indicated. -t? o Common variable immunodeficiency can be diag- IE l,I nosed in persons with documented low IgG levels, Bibliography L (, impaired antibody production to pneumococcal or Berbari EFi, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of Ut tetanus vaccines, and variably decreased IgA and IgM America (IDSA) clinical practice guidelines for the diagnosis and treat- = E ment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015; antibody levels. 67 : e26 - 46. [PM I O, 26229122) doi : 1 0. 1 09 3 /c id I civ 482 Bibliography Ameratunga R, Woon ST. Perspective: evolving concepts in the diagnosis Item 29 Answer: C and understanding of common variable immunodeficiency disorders (CVID). Clin Rev Allergz Immunol. 2019. [PMID: StZZOgZt] doi:10.1007i Educational Objective: Prevent HIV infection in a s12016 019 08765-6 person who injects drugs.

Bibliography Ameratunga R, Woon ST. Perspective: evolving concepts in the diagnosis Item 29 Answer: C and understanding of common variable immunodeficiency disorders (CVID). Clin Rev Allergz Immunol. 2019. [PMID: StZZOgZt] doi:10.1007i Educational Objective: Prevent HIV infection in a s12016 019 08765-6 person who injects drugs. The most appropriate additional management is to initiate Item 28 tr Answer: C Ed ucationa I O bjective: Treat vertebral osteomyelitis HIV pre-exposure prophylaxis (PrEP) with tenofovir diso- proxil fumarate (TDF) and emtricitabine (Option C). Persons at high risk of HIV acquisition who should be considered for with a positive blood culture. PrEP include men who have sex with fl1€rl; fir€rl and women Vancomycin is the most appropriate initial management with a serodiscordant sexual partner; inconsistent condom for this patient (Option C). He has MRI evidence of disci- use with a partner whose HIV status is unknown or is at tis (increased signal intensity. disk space narrovr,'ing at the high risk; slphilis or gonorrhea infection within the previous L3 L4 disk space) with vertebral osteonryelitis (loss of end 6 months; and persons who share drug injection equipment. plate definition) and positive blood cultures. Although he is This patient shares drug injection equipment and should be hemodynamically stable, antibiotic therapy should be started considered for PrEP with the two-drug combination of TDF promptly based on the blood culture results. Patients receiving and emtricitabine, taken once daily. hemodialysis are at increased risk for ver-tebral osteomyelitis Persons taking PrEP who test positive for HIV should because of an increased risk of bacteremia from their clialysis have a third drug (either ritonavir-boosted darunavir or access. Staphylococcus aureus is the rnost likely pathogen dolutegravir) added to the two-drug PrEP regimen pending in adults with vertebral osteomyelitis, and the preliminary results of HIV RNA and viral resistance testing (Option A). A identification of the organism as coagulase-positive staphylo- three drug regimen cannot be recommended for this patient cocci supports this diagnosis. S. ourcus infections in patients who has no evidence of HIV infection. receiving hemodialysis are health care associated infbctions, In 2019, once-daily tenofovir alafenamide (TAF) and so the risk of methicillin resistant isolates is increased: vsn emtricitabine was approved for HIV PrEP for men at high comycin is appropriate empiric therapy pending additional risk. The efficacy of TAF-emtricitabine for PrEP in women susceptibility testing of the blood culture isolate. who engage in receptive vaginal sex and persons who inject In patients with vertebral osteomyelitis and positive drugs is unknown, so it is not recommended at this time. blood cultures for a typical pathogen, bone biopsy is gener- Additionally, tenofovir and emtricitabine-based regimens ally not indicated (Option A). Bone biopsy may still be rec- have been shown to have higher efflcacy than tenofovir ommended in persons who inject drugs. even with positive alone for PrEP; neither TDF nor TAF monotherapy is recom- blood cultures; these persons have frequent bacteremias, so mended for PrEP (Option B). the pathogen isolated in the blood stream may be different PrEP has been associated with a reduction in HIV trans- from that isolated from the vertebral infection. mission in groups of persons at high HIV risk, including

The most appropriate additional management is to initiate Item 28 tr Answer: C Ed ucationa I O bjective: Treat vertebral osteomyelitis HIV pre-exposure prophylaxis (PrEP) with tenofovir diso- proxil fumarate (TDF) and emtricitabine (Option C). Persons at high risk of HIV acquisition who should be considered for with a positive blood culture. PrEP include men who have sex with fl1€rl; fir€rl and women Vancomycin is the most appropriate initial management with a serodiscordant sexual partner; inconsistent condom for this patient (Option C). He has MRI evidence of disci- use with a partner whose HIV status is unknown or is at tis (increased signal intensity. disk space narrovr,'ing at the high risk; slphilis or gonorrhea infection within the previous L3 L4 disk space) with vertebral osteonryelitis (loss of end 6 months; and persons who share drug injection equipment. plate definition) and positive blood cultures. Although he is This patient shares drug injection equipment and should be hemodynamically stable, antibiotic therapy should be started considered for PrEP with the two-drug combination of TDF promptly based on the blood culture results. Patients receiving and emtricitabine, taken once daily. hemodialysis are at increased risk for ver-tebral osteomyelitis Persons taking PrEP who test positive for HIV should because of an increased risk of bacteremia from their clialysis have a third drug (either ritonavir-boosted darunavir or access. Staphylococcus aureus is the rnost likely pathogen dolutegravir) added to the two-drug PrEP regimen pending in adults with vertebral osteomyelitis, and the preliminary results of HIV RNA and viral resistance testing (Option A). A identification of the organism as coagulase-positive staphylo- three drug regimen cannot be recommended for this patient cocci supports this diagnosis. S. ourcus infections in patients who has no evidence of HIV infection. receiving hemodialysis are health care associated infbctions, In 2019, once-daily tenofovir alafenamide (TAF) and so the risk of methicillin resistant isolates is increased: vsn emtricitabine was approved for HIV PrEP for men at high comycin is appropriate empiric therapy pending additional risk. The efficacy of TAF-emtricitabine for PrEP in women susceptibility testing of the blood culture isolate. who engage in receptive vaginal sex and persons who inject In patients with vertebral osteomyelitis and positive drugs is unknown, so it is not recommended at this time. blood cultures for a typical pathogen, bone biopsy is gener- Additionally, tenofovir and emtricitabine-based regimens ally not indicated (Option A). Bone biopsy may still be rec- have been shown to have higher efflcacy than tenofovir ommended in persons who inject drugs. even with positive alone for PrEP; neither TDF nor TAF monotherapy is recom- blood cultures; these persons have frequent bacteremias, so mended for PrEP (Option B). the pathogen isolated in the blood stream may be different PrEP has been associated with a reduction in HIV trans- from that isolated from the vertebral infection. mission in groups of persons at high HIV risk, including 153

Answers and Critiques persons who inject drugs. PrEP, along with access to clean inr,olves the apical-posterior segments of the upper lobes needles and equipment and referral to substance abuse in most patients. However, rnicrobiologic differentiation treatment, is indicated in this patient rather than no addi- befween organisms is imperative because treatment differs' tional management (OPtion D). Streptococcus pneumoniae (Option D) is a gram- positive, lancet-shaped bacteria that is the most com I(EY POITT mon bacterial cause of community-acquired pneumonia' . Tenofovir disoproxil fumarate and emtricitabine, taken However, it usually produces an acute infectious process. once daily, is the preferred regimen for women at high including acute pneumonia, bacteremia, sepsis. and not risk for HIV infection who engage in receptive vaginal ir-rfrequently death. It does not produce a chronic lung infec intercourse and for persons who inject drugs using tion or lung disease. Nonetheless, it is commonly seen as an shared equipment. acute infection in persons with underlying lung disease'

persons who inject drugs. PrEP, along with access to clean inr,olves the apical-posterior segments of the upper lobes needles and equipment and referral to substance abuse in most patients. However, rnicrobiologic differentiation treatment, is indicated in this patient rather than no addi- befween organisms is imperative because treatment differs' tional management (OPtion D). Streptococcus pneumoniae (Option D) is a gram- positive, lancet-shaped bacteria that is the most com I(EY POITT mon bacterial cause of community-acquired pneumonia' . Tenofovir disoproxil fumarate and emtricitabine, taken However, it usually produces an acute infectious process. once daily, is the preferred regimen for women at high including acute pneumonia, bacteremia, sepsis. and not risk for HIV infection who engage in receptive vaginal ir-rfrequently death. It does not produce a chronic lung infec intercourse and for persons who inject drugs using tion or lung disease. Nonetheless, it is commonly seen as an shared equipment. acute infection in persons with underlying lung disease' I(EY POIilI' D J Bibliography . MAcobacterium auium complex infection is a cavitary UT US Preventive Services Task Force, Owens DK. Davidson KW, Krist AH. et al. Preexposure prophylaxis for the prevention of HIV infection: US lung disease classically seen in older adult White men (D = rt Preventive Services Task Force Recommendation Statement. JAMA. 2019 with underlying lung disease (e.g., COPD) and a vt Jun il r321 (22\ :2203-2213. PMID: 31184747 o, smoking history. J CL o Fibrocavitary lung disease is a common radiographic rl -,tt Item 3O Answer: A .El ? tr Educational Objective: Diagnose a patient with presentatio n of My cobacterium au ium complex infection. .D UI pulmonary My cob acterium av ium complex infection. Bibliography 'lhe nrost likely diagnosis in this patient is Mycobacterium Daley CL. Mycobacterium avium complex disease. Microbiol Spectr. 2017r5 auiurn complex (MAC) infection (Option A). MAC is the most IPn'ltO, 28429 67 9) doi:10.1128/microbiolspec.TNMIT-0045-2017 common cause of chronic lung infection worldwide. Cavitary lung disease is seen classically in White, middle-aged, or older adult men, especially those with underlying lung disease. Item 31 Answer: A such as COPD, who smoke cigarettes. Additionally, because Educational Objective: Diagnose a deep/organ space of the relatively indolent nature of MAC lung disease. lung surgical site infection. destruction may be quite extetrsive at the time of diagnosis rvith very large cavities on chest radiograph. The infection This patient likely has a deep incisional or deep/organ space is fiequently associated with r,teight loss and night sr.tieats. infection, which should be evaluated by abdominal CT The chest radiograph generally reveals classic flbrocavitary (Option A). The risk of surgical site infection (SSI) associated changes, and respiratory secretions stain positive for acid-fast with laparoscopic cholecystectomy is lower than that with bacilli. The patient's negatire interferon yrelease assay (IGRA) open cholecystectomy, but acute cholecystitis or common bile further supports a diagnosis of nontuberculous mycobac duct stones signiflcantly increases the risk of SSI with laparo- terial infection. The dellnitive diagnosis would be achie"ad scopic cholecystectomy. Most SSIs occur within 30 days fol- by nucleic acid amplification testing or molecular probe to lowing surgery (oo days for surgery involving placement of an further identi$, the mycobacteria and grorn, the organism fbr implant). SSIs are categorized as superficial incisional, deep susceptibility testing. A variant of MAC lung disease seen in incisional, and deepiorgan space infections. Deep incisional \ ,'omen older than 50 years r,r'ho derrelop bronchiectasis is (involving fascia andior muscle layers) SSIs and deep/organ termed nodular or bronchiectatic MAC because nodules and space (tissue deep to the fascia) infections usually present bronchiectasis are typically seen on chest radiograph. with systemic signs of infection such as fever and leukocyto- Mycobacteriurn rnarinum (Option B) rnould be sis. Differentiating between the two types of infection based unlikely in this patient. It is a slow-growing. nontuberculous on examination alone can be difficult, so imaging is necessary. mycobacterium associated with handling flsh and cleaning CT is useful for identiffing deep/organ space SSI abscesses and aquariums. M. marinunr is in the same group as MAC, M. planning necessary drainage procedures, including obtaining ulcerans, and M. scrofulaceum; however, this organism is material for culture to guide deflnitive antibiotic therapy. Bac generally associated with ulcerative cutaneous infections teremia may occur with deepiorgan space infections, so blood and skin and soft tissne infections. not lung disease. cultures should also be considered. Although Mycobacteriunt tuberculosis (Option C) A superflcial incisional infection involves the under should be an initial consideration in the differential diagno- lying soft tissue and presents with inflammatory changes sis, the patient's medical history and negative IGRA indicate at the incision site (e.g., erythema, tenderness), with or likely MAC infection rather than M. tuberculosis. Addition without purulent drainage, and few if any systemic signs of ally, in primary pulmonary tuberculosis infection. common infection such as fever. Cephalexin (Option B) is an accept radiographic changes include hilar lymphadenopathy and able antibiotic option for a superflcial incisional infection, pulmonary infiltrates. Reactivation tuberculosis typically which commonly involves skin flora, but it is best to wait

I(EY POIilI' D J Bibliography . MAcobacterium auium complex infection is a cavitary UT US Preventive Services Task Force, Owens DK. Davidson KW, Krist AH. et al. Preexposure prophylaxis for the prevention of HIV infection: US lung disease classically seen in older adult White men (D = rt Preventive Services Task Force Recommendation Statement. JAMA. 2019 with underlying lung disease (e.g., COPD) and a vt Jun il r321 (22\ :2203-2213. PMID: 31184747 o, smoking history. J CL o Fibrocavitary lung disease is a common radiographic rl -,tt Item 3O Answer: A .El ? tr Educational Objective: Diagnose a patient with presentatio n of My cobacterium au ium complex infection. .D UI pulmonary My cob acterium av ium complex infection. Bibliography 'lhe nrost likely diagnosis in this patient is Mycobacterium Daley CL. Mycobacterium avium complex disease. Microbiol Spectr. 2017r5 auiurn complex (MAC) infection (Option A). MAC is the most IPn'ltO, 28429 67 9) doi:10.1128/microbiolspec.TNMIT-0045-2017 common cause of chronic lung infection worldwide. Cavitary lung disease is seen classically in White, middle-aged, or older adult men, especially those with underlying lung disease. Item 31 Answer: A such as COPD, who smoke cigarettes. Additionally, because Educational Objective: Diagnose a deep/organ space of the relatively indolent nature of MAC lung disease. lung surgical site infection. destruction may be quite extetrsive at the time of diagnosis rvith very large cavities on chest radiograph. The infection This patient likely has a deep incisional or deep/organ space is fiequently associated with r,teight loss and night sr.tieats. infection, which should be evaluated by abdominal CT The chest radiograph generally reveals classic flbrocavitary (Option A). The risk of surgical site infection (SSI) associated changes, and respiratory secretions stain positive for acid-fast with laparoscopic cholecystectomy is lower than that with bacilli. The patient's negatire interferon yrelease assay (IGRA) open cholecystectomy, but acute cholecystitis or common bile further supports a diagnosis of nontuberculous mycobac duct stones signiflcantly increases the risk of SSI with laparo- terial infection. The dellnitive diagnosis would be achie"ad scopic cholecystectomy. Most SSIs occur within 30 days fol- by nucleic acid amplification testing or molecular probe to lowing surgery (oo days for surgery involving placement of an further identi$, the mycobacteria and grorn, the organism fbr implant). SSIs are categorized as superficial incisional, deep susceptibility testing. A variant of MAC lung disease seen in incisional, and deepiorgan space infections. Deep incisional \ ,'omen older than 50 years r,r'ho derrelop bronchiectasis is (involving fascia andior muscle layers) SSIs and deep/organ termed nodular or bronchiectatic MAC because nodules and space (tissue deep to the fascia) infections usually present bronchiectasis are typically seen on chest radiograph. with systemic signs of infection such as fever and leukocyto- Mycobacteriurn rnarinum (Option B) rnould be sis. Differentiating between the two types of infection based unlikely in this patient. It is a slow-growing. nontuberculous on examination alone can be difficult, so imaging is necessary. mycobacterium associated with handling flsh and cleaning CT is useful for identiffing deep/organ space SSI abscesses and aquariums. M. marinunr is in the same group as MAC, M. planning necessary drainage procedures, including obtaining ulcerans, and M. scrofulaceum; however, this organism is material for culture to guide deflnitive antibiotic therapy. Bac generally associated with ulcerative cutaneous infections teremia may occur with deepiorgan space infections, so blood and skin and soft tissne infections. not lung disease. cultures should also be considered. Although Mycobacteriunt tuberculosis (Option C) A superflcial incisional infection involves the under should be an initial consideration in the differential diagno- lying soft tissue and presents with inflammatory changes sis, the patient's medical history and negative IGRA indicate at the incision site (e.g., erythema, tenderness), with or likely MAC infection rather than M. tuberculosis. Addition without purulent drainage, and few if any systemic signs of ally, in primary pulmonary tuberculosis infection. common infection such as fever. Cephalexin (Option B) is an accept radiographic changes include hilar lymphadenopathy and able antibiotic option for a superflcial incisional infection, pulmonary infiltrates. Reactivation tuberculosis typically which commonly involves skin flora, but it is best to wait 154

Answers and Critiques until culture results are available to initiate antibiotics. More infection. Not following these measures increases the risk for importantly, this patient does not have a superflcial inci development of a CLABSI. sional infection, but a deep incisional or deep/organ space Random blood cultures from the f'emoral catheter infection, for which cephalexin would be inadequate. (Option A) are not appropriate fbr monitoring fbr the clevel A superflcial incisional infection may need to be opment of CVC infections. The risk of blood culture con reopened to determine the extent of infection, allow com- tamination is high. making the results difficult to interpret plete drainage, and obtain proper specimens for Gram stain (colonization vs infbction). and culture to guide antibiotic therapy. A superflcial swab Monitoring patients fbr CLABSIs (Option B) is impor of the incision site drainage (Option C) is not adequate for tant but is not a substitute for replacing a CVC that r,vas determining organisms causing deeper infections. inserted emergently <tr under less than optirnal conditions. Empiric therapy with piperacillin-tazobactam (Option Guidelines recommend against changing CVCs over a D) is not warranted in a stable patient before deep tissue/ guidewire (Option C) because this increases the risk of abscess cultures have been obtained. bloodstream infection by introducing bacteria fronr the skin ta o, t(EY P0l]tTS at the time of insertion. - J ET .I

until culture results are available to initiate antibiotics. More infection. Not following these measures increases the risk for importantly, this patient does not have a superflcial inci development of a CLABSI. sional infection, but a deep incisional or deep/organ space Random blood cultures from the f'emoral catheter infection, for which cephalexin would be inadequate. (Option A) are not appropriate fbr monitoring fbr the clevel A superflcial incisional infection may need to be opment of CVC infections. The risk of blood culture con reopened to determine the extent of infection, allow com- tamination is high. making the results difficult to interpret plete drainage, and obtain proper specimens for Gram stain (colonization vs infbction). and culture to guide antibiotic therapy. A superflcial swab Monitoring patients fbr CLABSIs (Option B) is impor of the incision site drainage (Option C) is not adequate for tant but is not a substitute for replacing a CVC that r,vas determining organisms causing deeper infections. inserted emergently <tr under less than optirnal conditions. Empiric therapy with piperacillin-tazobactam (Option Guidelines recommend against changing CVCs over a D) is not warranted in a stable patient before deep tissue/ guidewire (Option C) because this increases the risk of abscess cultures have been obtained. bloodstream infection by introducing bacteria fronr the skin ta o, t(EY P0l]tTS at the time of insertion. - J ET .I o Most surgical site infections occur within 30 days fol- t(EV POtilTt .Z L lowing surgery (eO days for surgery involving placement o Central venous catheters inserted under emergency t, E of an implant). conditions should be removed as soon as possible (no E .E . Deep/organ space surgical site infections usually longer than 48 hours after insertion) and replaced at a UT L new site. c, present with systemic signs of infection such as fever UI and leukocytosis, and imaging with CT is necessary to o The need for continued use of central venous catheters = L identiff abscesses and plan drainage and specimen should be reviewed and documented daily. collection. Bibliography Bibliography Patel PK, Olmsted RN, Hung L, et al. A tiered approach for preventing central line-associated bloodstream infection. Ann Intern Med. 2019;171:516- Garner BH, Anderson DJ. Surgical site infections: an update. Infect Dis Clin S22. [PMID: SLSOSZZS) doi:10.7326lM18 3469 North Am. 2016;30:909-929. [PMID: ZZArctqZ] doi:10.1016/j.idc.2016. 07.010

o Most surgical site infections occur within 30 days fol- t(EV POtilTt .Z L lowing surgery (eO days for surgery involving placement o Central venous catheters inserted under emergency t, E of an implant). conditions should be removed as soon as possible (no E .E . Deep/organ space surgical site infections usually longer than 48 hours after insertion) and replaced at a UT L new site. c, present with systemic signs of infection such as fever UI and leukocytosis, and imaging with CT is necessary to o The need for continued use of central venous catheters = L identiff abscesses and plan drainage and specimen should be reviewed and documented daily. collection. Bibliography Bibliography Patel PK, Olmsted RN, Hung L, et al. A tiered approach for preventing central line-associated bloodstream infection. Ann Intern Med. 2019;171:516- Garner BH, Anderson DJ. Surgical site infections: an update. Infect Dis Clin S22. [PMID: SLSOSZZS) doi:10.7326lM18 3469 North Am. 2016;30:909-929. [PMID: ZZArctqZ] doi:10.1016/j.idc.2016. 07.010 Item 33 tr Item 32 Answer: D Answer: C Educational Objective: Treat disseminated tr Educational Objective: Prevent central venous catheter- histoplasmosis. associated bloodstream infection. The most appropriate treatment for this patient is liposo Central venous catheters (CVCs) inserted under emergency mal amphotericin t3 (Option C) for disseminated histo conditions should be removed as soon as possible (no longer plasnrosis. The Histoplasma urinary antigen assay has a than 48 hours after insertion) and replaced at a new site sensitivity and specificity of greater than 85'1, in acute and (Option D). Femoral 'uenous catheters are associated with disseminated ir-rfection but less than 50'/,, in chronic infec- higher rates of infection and should be avoided. if possible. tion. ldentiflcation of the fungus by tissue culture can be Aseptic technique and following the CVC insertion bundle a lengthy process but is indicated for clinically suspected decrease the risk of central line-associated bloodstream cases in which the urinary antigen assay result is negative. infections (CLABSIs), but these strategies are not assured The peripheral blood smear alscl shows yeast cells within a when a CVC is placed emergently. The CVC insertion bundle leukocyte, characteristic of disseminated histoplasmosis. includes hand hygiene; use of full barrier precautions (large Furthermore, the patient has several risk f:rctors, inclucling full bodl' sterile drape to cover the patient during cathe living in an endemic area and takir-rg immunosuppres ter insertion) and personal protective equipment (mask, sant medication; treatment with tumor necrosis factor-cr cap, sterile gown, and gloves); chlorhexidine skin antisepsis inhibitors (e.9., infliximab. etanercept, adalimurnab) is an (allow' antiseptic to air dry before beginning procedure); increasingly recognized cause of disseminated histoplas optimal site selection and catheter type (e.g., minimum mosis in patients with rheumatoid arthritis. The abnormal number of ports or lumens needed): sterile dressing; and chest radiograph with bilateral infiltrates and hepatospleno daily review of necessity, with prompt removal of unneces- megaly also indicate infection with Histoplosnio. Finally, sary catheters. The daily review of line necessity and docu- thrombocytopenia and anemia are also characteristic of' mentation can be achieved with multidisciplinary rounds, histoplasmosis. If disseminated histoplasntosis is not diag daily reminders, and automated alerts. These practices are nosed and treated early. patients can develop septic shock. important in decreasing the risk of developing CLABSIs. which has a mortality rate as high as 90'X,. The treatment Additionally, hand hygiene before manipulation of the intra of choice remains liposomal amphotericin B; however, oral venous system, care of injection ports, and proper catheter itraconazole can be used to complete therapy after improve site dressing monitoring and dressing changes reduce risk of ment is shown.

Item 33 tr Item 32 Answer: D Answer: C Educational Objective: Treat disseminated tr Educational Objective: Prevent central venous catheter- histoplasmosis. associated bloodstream infection. The most appropriate treatment for this patient is liposo Central venous catheters (CVCs) inserted under emergency mal amphotericin t3 (Option C) for disseminated histo conditions should be removed as soon as possible (no longer plasnrosis. The Histoplasma urinary antigen assay has a than 48 hours after insertion) and replaced at a new site sensitivity and specificity of greater than 85'1, in acute and (Option D). Femoral 'uenous catheters are associated with disseminated ir-rfection but less than 50'/,, in chronic infec- higher rates of infection and should be avoided. if possible. tion. ldentiflcation of the fungus by tissue culture can be Aseptic technique and following the CVC insertion bundle a lengthy process but is indicated for clinically suspected decrease the risk of central line-associated bloodstream cases in which the urinary antigen assay result is negative. infections (CLABSIs), but these strategies are not assured The peripheral blood smear alscl shows yeast cells within a when a CVC is placed emergently. The CVC insertion bundle leukocyte, characteristic of disseminated histoplasmosis. includes hand hygiene; use of full barrier precautions (large Furthermore, the patient has several risk f:rctors, inclucling full bodl' sterile drape to cover the patient during cathe living in an endemic area and takir-rg immunosuppres ter insertion) and personal protective equipment (mask, sant medication; treatment with tumor necrosis factor-cr cap, sterile gown, and gloves); chlorhexidine skin antisepsis inhibitors (e.9., infliximab. etanercept, adalimurnab) is an (allow' antiseptic to air dry before beginning procedure); increasingly recognized cause of disseminated histoplas optimal site selection and catheter type (e.g., minimum mosis in patients with rheumatoid arthritis. The abnormal number of ports or lumens needed): sterile dressing; and chest radiograph with bilateral infiltrates and hepatospleno daily review of necessity, with prompt removal of unneces- megaly also indicate infection with Histoplosnio. Finally, sary catheters. The daily review of line necessity and docu- thrombocytopenia and anemia are also characteristic of' mentation can be achieved with multidisciplinary rounds, histoplasmosis. If disseminated histoplasntosis is not diag daily reminders, and automated alerts. These practices are nosed and treated early. patients can develop septic shock. important in decreasing the risk of developing CLABSIs. which has a mortality rate as high as 90'X,. The treatment Additionally, hand hygiene before manipulation of the intra of choice remains liposomal amphotericin B; however, oral venous system, care of injection ports, and proper catheter itraconazole can be used to complete therapy after improve site dressing monitoring and dressing changes reduce risk of ment is shown. 155

Answers and Critiques m Fluconazole (Option A) has been used in patients cause of vertebral osteomyelitis in adults is Stophylococ- lll n'ho could not take amphotericin B 1f i11 histoplasmosis cus aLtreus: streptococcal species, Enterobacteriaceae. and CONT or itraconazole. However. fluconazole is not as eflective as Candida species can also be seen. However, this older man either amphotericin B or itraconazole and clears fungemia rt ith benign prostatic hyperplasia and risk for urinary tract more slowly. The der,elopment of resistance also makes flu infections could be infected with gram-negative patho- conazole a much less desirable therapy. gens. so empiric antibiotics with broad coverage for gram- Itraconazole (Option B) can be used as monother- positive and gram-negative pathogens, such as vancomycin apy for patients with mild to moderate disease caused and ceftriaxone (Option D), would be more appropriate than by histoplasmosis. However, itraconazole does not clear vancomlcin alone (Option C) if empiric antibiotics were fungemia as quickly as amphotericin B and is. therefore. indicated. not a first-line agent in patients with severe or dissemi- t(EY P0tilTS nated histoplasmosis. Posaconazole (Option D) is a triazole antifungal used to o Initiation of antibiotic therapy for uncomplicated ver- D )UI- treat many invasive fungal inf'ections. including aspergillosis tebral osteomyelitis is based on culture results. E (D and mucormycosis. Flowever. it has not been fully evaluated o Image-guided biopsy has a diagnostic yield of approx- - UI in any form of histoplasmosis. It may be useful in certain imately 60o/o for vertebral osteomyelitis and should be o, situations when itraconazole or liposomal amphotericin B J used in patients with negative blood culture results. CL cannot be used. but it is not a flrst line treatment choice. n ql Bibliography r+ -a I(EY POITIS ll -a o The Histoplosmo urinary antigen assay has a sensitivity Berbari EE, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of E (D America (IDSA) clinical practice guidelines for the diagnosis and treat UI and specificity of greater than 85% in acute and dis- ment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61: e26 - 46. [ptr,tlO, 26229722] doi:10.1093 /cid/civ482 seminated infection. o The treatment of choice for disseminated histoplasmosis is liposomal amphotericin B. Item 35 Answer: B : Diagnose Comp ylobacter- Ed u cati o n a I O bi ective Bibliography related Guillain -Barrd syndrome. Wheat Ll, Azar MM, Bahr NC, et al. Histoplasmosis. Infect Dis CIin North Am. 2016;30: 2o7 -27. [PMID: 26897068] doi:10.1016/j.idc.2015.10.009 This patient has developed Guillain-Barrd syndrome (GBS) after a gastrointestinal infection; Campylobacter is the most commonly diagnosed trigger of GBS (Option B). In the United Item 34 tr Answer: A Ed ucational Objective: Evaluate vertebral osteomyelitis States, an estimated 10% to 40% of GBS results from Campy- lobacter or Campylobacter-like diarrheal illness. This acute demyelinating polyradiculoneuropathy is thought to result with needle biopsy. from autoantibodies directed against the infecting organism Disk space aspiration and biopsy is the most appropriate next that also cross-react with neuronal tissue. Other less common step in the management of this patient with evidence of disci- infectious triggers include Epstein-Barr virus, cytomegalovi- tis and osteomyelitis involving the spine (Option A). Although rus, Zika virus, and HIV as well as respiratory influenza-like mildly febrile with leukocytosis. he is hemodynamically sta infections. GBS symptoms usually develop 1to 3 weeks after ble. so antibiotic therapy may be safely withheld until a speci- Campylobocter-associated diarrhea begins. Symmetric weak- men is obtained for culture. Because the treatment duration is ness typically begins in the lower extremities before ascending long. generally 6 weeks, and the risk of adverse events is high, to the upper limbs and respiratory and bulbar muscles. Low especially in older patients. every eflort should be made to back pain and paresthesias are common, and patients may ensure that the antibiotic selected is optimal for the organism exhibit dysautonomiawith arrhythmias and labile blood pres causing the infection. If blood cultures return positive for a sures; respiratory failure may develop. In addition to flaccid typical pathogen, the need for biopsy could be reassessed. If paralysis, the physical examination typically reveals diffuse neurologic compromise or radiographic evidence of spinal areflexia and little sensory loss. Treatment consists of either instability were present. urgent surgical intervention may be plasmapheresis or intravenous immune globulin. needed. Botulism (Option A) is a toxin-mediated disease The yield of percutaneous biopsy in this setting is acquired from ingestion or wound contamination. Within around 60"/,,. lf the first biopsy is negative, a second attempt 5 days of exposure, patients develop a classic triad of at percutaneous biopsy can be made before considering descending flaccid paralysis with prominent bulbar palsies, open biopsy (Option B). normal mental status, and normal body temperature. Bulbar Indications to begin empiric antibiotic therapy include signs include the "4 Ds": dysarthria, dysphonia, dysphagia, hemodynamic instability. epidural abscess, signs of spi- and diplopia. Diagnostic conflrmation relies on identi$zing nal instability, and progressive neurologic deflcit, none of the botulinum toxin. Antitoxin therapy and supportive care which are present in this patient. The most likely microbial should be provided.

m Fluconazole (Option A) has been used in patients cause of vertebral osteomyelitis in adults is Stophylococ- lll n'ho could not take amphotericin B 1f i11 histoplasmosis cus aLtreus: streptococcal species, Enterobacteriaceae. and CONT or itraconazole. However. fluconazole is not as eflective as Candida species can also be seen. However, this older man either amphotericin B or itraconazole and clears fungemia rt ith benign prostatic hyperplasia and risk for urinary tract more slowly. The der,elopment of resistance also makes flu infections could be infected with gram-negative patho- conazole a much less desirable therapy. gens. so empiric antibiotics with broad coverage for gram- Itraconazole (Option B) can be used as monother- positive and gram-negative pathogens, such as vancomycin apy for patients with mild to moderate disease caused and ceftriaxone (Option D), would be more appropriate than by histoplasmosis. However, itraconazole does not clear vancomlcin alone (Option C) if empiric antibiotics were fungemia as quickly as amphotericin B and is. therefore. indicated. not a first-line agent in patients with severe or dissemi- t(EY P0tilTS nated histoplasmosis. Posaconazole (Option D) is a triazole antifungal used to o Initiation of antibiotic therapy for uncomplicated ver- D )UI- treat many invasive fungal inf'ections. including aspergillosis tebral osteomyelitis is based on culture results. E (D and mucormycosis. Flowever. it has not been fully evaluated o Image-guided biopsy has a diagnostic yield of approx- - UI in any form of histoplasmosis. It may be useful in certain imately 60o/o for vertebral osteomyelitis and should be o, situations when itraconazole or liposomal amphotericin B J used in patients with negative blood culture results. CL cannot be used. but it is not a flrst line treatment choice. n ql Bibliography r+ -a I(EY POITIS ll -a o The Histoplosmo urinary antigen assay has a sensitivity Berbari EE, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of E (D America (IDSA) clinical practice guidelines for the diagnosis and treat UI and specificity of greater than 85% in acute and dis- ment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61: e26 - 46. [ptr,tlO, 26229722] doi:10.1093 /cid/civ482 seminated infection. o The treatment of choice for disseminated histoplasmosis is liposomal amphotericin B. Item 35 Answer: B : Diagnose Comp ylobacter- Ed u cati o n a I O bi ective Bibliography related Guillain -Barrd syndrome. Wheat Ll, Azar MM, Bahr NC, et al. Histoplasmosis. Infect Dis CIin North Am. 2016;30: 2o7 -27. [PMID: 26897068] doi:10.1016/j.idc.2015.10.009 This patient has developed Guillain-Barrd syndrome (GBS) after a gastrointestinal infection; Campylobacter is the most commonly diagnosed trigger of GBS (Option B). In the United Item 34 tr Answer: A Ed ucational Objective: Evaluate vertebral osteomyelitis States, an estimated 10% to 40% of GBS results from Campy- lobacter or Campylobacter-like diarrheal illness. This acute demyelinating polyradiculoneuropathy is thought to result with needle biopsy. from autoantibodies directed against the infecting organism Disk space aspiration and biopsy is the most appropriate next that also cross-react with neuronal tissue. Other less common step in the management of this patient with evidence of disci- infectious triggers include Epstein-Barr virus, cytomegalovi- tis and osteomyelitis involving the spine (Option A). Although rus, Zika virus, and HIV as well as respiratory influenza-like mildly febrile with leukocytosis. he is hemodynamically sta infections. GBS symptoms usually develop 1to 3 weeks after ble. so antibiotic therapy may be safely withheld until a speci- Campylobocter-associated diarrhea begins. Symmetric weak- men is obtained for culture. Because the treatment duration is ness typically begins in the lower extremities before ascending long. generally 6 weeks, and the risk of adverse events is high, to the upper limbs and respiratory and bulbar muscles. Low especially in older patients. every eflort should be made to back pain and paresthesias are common, and patients may ensure that the antibiotic selected is optimal for the organism exhibit dysautonomiawith arrhythmias and labile blood pres causing the infection. If blood cultures return positive for a sures; respiratory failure may develop. In addition to flaccid typical pathogen, the need for biopsy could be reassessed. If paralysis, the physical examination typically reveals diffuse neurologic compromise or radiographic evidence of spinal areflexia and little sensory loss. Treatment consists of either instability were present. urgent surgical intervention may be plasmapheresis or intravenous immune globulin. needed. Botulism (Option A) is a toxin-mediated disease The yield of percutaneous biopsy in this setting is acquired from ingestion or wound contamination. Within around 60"/,,. lf the first biopsy is negative, a second attempt 5 days of exposure, patients develop a classic triad of at percutaneous biopsy can be made before considering descending flaccid paralysis with prominent bulbar palsies, open biopsy (Option B). normal mental status, and normal body temperature. Bulbar Indications to begin empiric antibiotic therapy include signs include the "4 Ds": dysarthria, dysphonia, dysphagia, hemodynamic instability. epidural abscess, signs of spi- and diplopia. Diagnostic conflrmation relies on identi$zing nal instability, and progressive neurologic deflcit, none of the botulinum toxin. Antitoxin therapy and supportive care which are present in this patient. The most likely microbial should be provided. 156

Answers and Critiques West Nile virus (Option C) is transmitted by Culex inhibiting the adherence of Escherichia coli to uroepithe- mosquitoes during the summer or early fall. Neuroinvasive lial cells, lack randomized clinical trial conflrmation. disease occurs in less than 17, of infected persons, usually in Adhesion blockers such as D-mannose (Option B), the- those older than 50 years or immunocompromised trans orized to block E. coli adhesion to mannosylated uroepithe- plant recipients. The clinical presentation may manifest as lial receptors, have not been tested in clinical trials. an encephalitis, meningitis, or acute asymmetric flaccid Antimicrobial prophylaxis should be reserved paralysis with associated respiratory failure that resembles for women with frequent recurrent cystitis, deflned as poliomyelitis. three or more infections within 12 months, that has not Zika virus infection (Option D) is transmitted by Aedes lessened after attempts using nonantimicrobial strategies. mosquitoes or through sexual contact. Symptomatic infec Placebo-controlled trials using nightly doses of antibiotics tion is associated with fever, rash, headache, and arthralgia; demonstrated an approximate 95'ln reduction in infection conjunctivitis is often noted. Most patients have self-limited recurrence. A 6-month trial is recommended; however, illness lasting about 1 week, although some patients may the previous pattern of recurrent infection occurs in UI develop GBS. It is unlikely that this patient, who has been nearly 50% of women when antibiotic prophylaxis is o d ET sexually abstinent and without a history of travel, has Zika discontinued. Preferred prophylactic regimens include P .E virus infection. nitrofurantoin (50-100 mg), trimethoprim-sulfamethoxazole L L' (single strength), and cephalexin (12s-250 mg). Ciprofloxacin 'E I(EY POI IT s (Option C) or other fluoroquinolone antibiotics are no longer llt . CampAlobacteris the most commonly diagnosed trigger recommended because of long-term safety concerns. Ut L of Guillain-Barre qrndrome; less common infectious (l, Urination soon after sexual intercourse (Option E) is triggers include Epstein-Barr virus, cytomegalovirus, often recommended but is an unproven strategz to prevent U) = ? Zika virus, and HIV recurrent UTI.

West Nile virus (Option C) is transmitted by Culex inhibiting the adherence of Escherichia coli to uroepithe- mosquitoes during the summer or early fall. Neuroinvasive lial cells, lack randomized clinical trial conflrmation. disease occurs in less than 17, of infected persons, usually in Adhesion blockers such as D-mannose (Option B), the- those older than 50 years or immunocompromised trans orized to block E. coli adhesion to mannosylated uroepithe- plant recipients. The clinical presentation may manifest as lial receptors, have not been tested in clinical trials. an encephalitis, meningitis, or acute asymmetric flaccid Antimicrobial prophylaxis should be reserved paralysis with associated respiratory failure that resembles for women with frequent recurrent cystitis, deflned as poliomyelitis. three or more infections within 12 months, that has not Zika virus infection (Option D) is transmitted by Aedes lessened after attempts using nonantimicrobial strategies. mosquitoes or through sexual contact. Symptomatic infec Placebo-controlled trials using nightly doses of antibiotics tion is associated with fever, rash, headache, and arthralgia; demonstrated an approximate 95'ln reduction in infection conjunctivitis is often noted. Most patients have self-limited recurrence. A 6-month trial is recommended; however, illness lasting about 1 week, although some patients may the previous pattern of recurrent infection occurs in UI develop GBS. It is unlikely that this patient, who has been nearly 50% of women when antibiotic prophylaxis is o d ET sexually abstinent and without a history of travel, has Zika discontinued. Preferred prophylactic regimens include P .E virus infection. nitrofurantoin (50-100 mg), trimethoprim-sulfamethoxazole L L' (single strength), and cephalexin (12s-250 mg). Ciprofloxacin 'E I(EY POI IT s (Option C) or other fluoroquinolone antibiotics are no longer llt . CampAlobacteris the most commonly diagnosed trigger recommended because of long-term safety concerns. Ut L of Guillain-Barre qrndrome; less common infectious (l, Urination soon after sexual intercourse (Option E) is triggers include Epstein-Barr virus, cytomegalovirus, often recommended but is an unproven strategz to prevent U) = ? Zika virus, and HIV recurrent UTI. t(EY POt ltTS Bibliography Halpin AL, Gu W, Wise ME, et al. Post Campylobacter Guillain Barre o In women with recurrent cystitis, self-treatment with Syndrome in the USA: secondary analysis of surveillance data collected a first-line, short-course regimen (such as nitrofuran- during the 2009-2010 novel Influenza A (H1N1) vaccination campaign. Epidemiol Infect. 2018; 146:174O -1745. [PMID: 299867771 doi:10.1017/ toin) is an appropriate initial strategr. s0950268818001802 . Nightly antimicrobial prophylaxis should be reserved for women with three or more urinary tract infections Item 36 Answer: D within 12 months. Ed ucationa I Objective: Treat recurrent cystitis. Bibliography Self treatment of each infection with nitrofurantoin is Kolman KB. Cystitis and pyelonephritis: diagnosis, treatment, and preven- appropriate for this patient (Option D). One-quarter to one- tion. Prim Care. 2Ot9 ;46:797-202. [PMID: STOSOSZO] doi:10.1016/j.pop. 2019.01.001 third of women who recover from an episode of cystitis will develop another symptomatic infection within 6 months. Recurrent infections that return within 2 weeks of flnishing Item 37 Answer: E appropriate antibiotic therapy for uncomplicated cystitis Educational Objective: Manage influenza with and involve the same cultured bacteria are categorized as supportive care. relapsed. Recurrent UTIs occurring weeks after successful antibiotic treatment and often involving bacterial strains The most appropriate management is supportive care (Option different from the original are termed reinfection This type E). This otherwise healthy patient at low risk of complications of recurrent UTI is deflned by three culture positive infec does not meet any indication for influenza testing or anti- tions in the previous 12 months or two infections within biotic or antiviral therapy. She will recover with attention to 6 months. Contributing factors for reinfection in premeno- hydration, antipyretics, and simple analgesia as needed. pausal women include sexual activity, diaphragm and Acute bronchitis is most commonly caused by a viral spermicide use, delayed urinary habits, and douching. infection, and treatment with antibiotics such as azilhro- Diminished estrogen levels and, to a lesser extent, increases mycin (Option A) does not hasten resolution of symptoms in residual bladder urine volume and incontinence play but can be associated with numerous deleterious outcomes, much larger roles in UTIs in postmenopausal women. Epi- including nausea, vomiting, diarrhea, rash, headache, vag- sodic self-diagnosis and treatment with a flrst-line, short- initis, and anaphylaxis. The number needed to harm with course regimen such as nitrofurantoin is an appropriate antibiotic prescribing has been calculated to be 24. initial strategz. Single-dose, postcoital antibiotics are effective The Infectious Disease Society of America (IDSA) recom- in reducing bladder infections if infection is temporally related mends that clinicians start antiviral treatment in outpatients to coitus; avoidance of spermicides has also proven beneflcial. of any age with severe or progressive illness, regardless of ill- Anecdotal claims of the beneflts of ingestion of daily ness duration; outpatients who are at high risk of complica- cranberry juice or tablets (Option A), presumably by tions from influenza, including those with chronic medical

t(EY POt ltTS Bibliography Halpin AL, Gu W, Wise ME, et al. Post Campylobacter Guillain Barre o In women with recurrent cystitis, self-treatment with Syndrome in the USA: secondary analysis of surveillance data collected a first-line, short-course regimen (such as nitrofuran- during the 2009-2010 novel Influenza A (H1N1) vaccination campaign. Epidemiol Infect. 2018; 146:174O -1745. [PMID: 299867771 doi:10.1017/ toin) is an appropriate initial strategr. s0950268818001802 . Nightly antimicrobial prophylaxis should be reserved for women with three or more urinary tract infections Item 36 Answer: D within 12 months. Ed ucationa I Objective: Treat recurrent cystitis. Bibliography Self treatment of each infection with nitrofurantoin is Kolman KB. Cystitis and pyelonephritis: diagnosis, treatment, and preven- appropriate for this patient (Option D). One-quarter to one- tion. Prim Care. 2Ot9 ;46:797-202. [PMID: STOSOSZO] doi:10.1016/j.pop. 2019.01.001 third of women who recover from an episode of cystitis will develop another symptomatic infection within 6 months. Recurrent infections that return within 2 weeks of flnishing Item 37 Answer: E appropriate antibiotic therapy for uncomplicated cystitis Educational Objective: Manage influenza with and involve the same cultured bacteria are categorized as supportive care. relapsed. Recurrent UTIs occurring weeks after successful antibiotic treatment and often involving bacterial strains The most appropriate management is supportive care (Option different from the original are termed reinfection This type E). This otherwise healthy patient at low risk of complications of recurrent UTI is deflned by three culture positive infec does not meet any indication for influenza testing or anti- tions in the previous 12 months or two infections within biotic or antiviral therapy. She will recover with attention to 6 months. Contributing factors for reinfection in premeno- hydration, antipyretics, and simple analgesia as needed. pausal women include sexual activity, diaphragm and Acute bronchitis is most commonly caused by a viral spermicide use, delayed urinary habits, and douching. infection, and treatment with antibiotics such as azilhro- Diminished estrogen levels and, to a lesser extent, increases mycin (Option A) does not hasten resolution of symptoms in residual bladder urine volume and incontinence play but can be associated with numerous deleterious outcomes, much larger roles in UTIs in postmenopausal women. Epi- including nausea, vomiting, diarrhea, rash, headache, vag- sodic self-diagnosis and treatment with a flrst-line, short- initis, and anaphylaxis. The number needed to harm with course regimen such as nitrofurantoin is an appropriate antibiotic prescribing has been calculated to be 24. initial strategz. Single-dose, postcoital antibiotics are effective The Infectious Disease Society of America (IDSA) recom- in reducing bladder infections if infection is temporally related mends that clinicians start antiviral treatment in outpatients to coitus; avoidance of spermicides has also proven beneflcial. of any age with severe or progressive illness, regardless of ill- Anecdotal claims of the beneflts of ingestion of daily ness duration; outpatients who are at high risk of complica- cranberry juice or tablets (Option A), presumably by tions from influenza, including those with chronic medical 157

Answers and Critiques conditions and immunocompromise; and pregnant women cryptococcal infection can also occur in otherwise healthy and those within 2 weeks postpartum. Antiviral treatment persons. The central nervous system is the most common can be considered for adult outpatients not at high risk for site of infection. CSF flndings include an increased leukocyte complications and illness onset no more than 2 days before count (mainly lymphocytes), an increased protein level, a low presentation. Other considerations for treatment include to normal glucose level, and the presence of cryptococcal anti- symptomatic outpatients who are household contacts of gen. Serum cryptococcal antigen is positive in greater than persons who are at high risk, particularly those who are 95o/,, of infected patients. Because the mortality rate is more severely immunocompromised, and symptomatic health than 50'/n in healthy patients, combination antifungal therapy care providers who care for patients who are at high risk, should be initiated immediately. After successful induction particularly those who are severely immunocompromised. therapy rryith amphotericin B and flucy'tosine, consolidation The patient is an otherwise healthy outpatient and will not therapy with fluconazole can be initiated. Many symptoms beneflt from treatment with either baloxavir or oseltamivir of increased intracranial pressure may be improved by CSF (Option B, D). removal through daily lumbar puncture or insertion of a J UI For the diagnosis of influenza, polymerase chain reac- shunt. Aggressive reduction of intracranial pressure reduces E tion testing (Option C) is preferred to rapid antigen test- early morbidity and mortality. .D - UT ing. The IDSA recommends that clinicians test for influenza This patient has a cryptococcal infection. Acyclovir q, - in patients at high risk, including immunocompromised (Option A) is used for infections caused by herpesviruses. CL persons who present with influenza-like illness, pneumo- including herpes simplex virus meningoencephalitis. n { nia, or nonspeciflc respiratory illness, if the testing result Caspofungin (Option B) is an echinocandin antifungal at'' -a

conditions and immunocompromise; and pregnant women cryptococcal infection can also occur in otherwise healthy and those within 2 weeks postpartum. Antiviral treatment persons. The central nervous system is the most common can be considered for adult outpatients not at high risk for site of infection. CSF flndings include an increased leukocyte complications and illness onset no more than 2 days before count (mainly lymphocytes), an increased protein level, a low presentation. Other considerations for treatment include to normal glucose level, and the presence of cryptococcal anti- symptomatic outpatients who are household contacts of gen. Serum cryptococcal antigen is positive in greater than persons who are at high risk, particularly those who are 95o/,, of infected patients. Because the mortality rate is more severely immunocompromised, and symptomatic health than 50'/n in healthy patients, combination antifungal therapy care providers who care for patients who are at high risk, should be initiated immediately. After successful induction particularly those who are severely immunocompromised. therapy rryith amphotericin B and flucy'tosine, consolidation The patient is an otherwise healthy outpatient and will not therapy with fluconazole can be initiated. Many symptoms beneflt from treatment with either baloxavir or oseltamivir of increased intracranial pressure may be improved by CSF (Option B, D). removal through daily lumbar puncture or insertion of a J UI For the diagnosis of influenza, polymerase chain reac- shunt. Aggressive reduction of intracranial pressure reduces E tion testing (Option C) is preferred to rapid antigen test- early morbidity and mortality. .D - UT ing. The IDSA recommends that clinicians test for influenza This patient has a cryptococcal infection. Acyclovir q, - in patients at high risk, including immunocompromised (Option A) is used for infections caused by herpesviruses. CL persons who present with influenza-like illness, pneumo- including herpes simplex virus meningoencephalitis. n { nia, or nonspeciflc respiratory illness, if the testing result Caspofungin (Option B) is an echinocandin antifungal at'' -a st -a will influence clinical management. Influenza testing can agent. It is the drug of choice for candidemia and invasive g be considered for patients not at high risk if the results candidiasis, but it has no activity against C. neoformans. .D tt might influence antiviral treatment decisions, reduce use of Additionally, echinocandins do not have adequate pene- unnecessary antibiotics, further diagnostic testing, or if the tration into the CSF or vitreous fluid to be effective for any results might influence antiviral treatment or chemoprophy- fungal central nervous system or ocular infection. laxis decisions for high-risk household contacts. Because the The combination of intravenous vancomycin and cef- patient lives alone, does not work in the health care environ triaxone (Option D) is recommended as empiric therapy for ment, and antiviral agents will not be initiated, the patient young, immunocompetent patients with possible community- has no indications for testing. acquired bacterial meningitis. However, this patient's Gram stain of the CSF revealed yeast, which eliminates the need for I( EY PO I TTS bacterial coverage. o Influenza testing can be considered for patients not at high risk for influenza complications if the results might influence antiviral treatment decisions. o Induction therapy for cryptococcal meningitis is lipo- o Antiviral influenza treatment can be considered for somal amphotericin B and flucfiosine; after successful adult outpatients not at high risk for complications induction therapy, fluconazole can be initiated for and illness onset no more than 2 days before presen- consolidation therapy. tation. o Aggressive reduction of intracranial pressure reduces early morbidity and mortality in patients with crypto- Bibliography coccal meningitis. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treat- ment, chemoprophylaxis, and institutional outbreak management of Bibliography seasonal influenza. Clin Infect Dis. 2019;68:el e47. [PMIO: SOSOOSOZ] Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2016;30: doi:10.1093 /cid/ciy866 77 9 20 6. [PMID : ZOegZ O 021 doi:10.1016 /j. idc. 2015. 10. 006

st -a will influence clinical management. Influenza testing can agent. It is the drug of choice for candidemia and invasive g be considered for patients not at high risk if the results candidiasis, but it has no activity against C. neoformans. .D tt might influence antiviral treatment decisions, reduce use of Additionally, echinocandins do not have adequate pene- unnecessary antibiotics, further diagnostic testing, or if the tration into the CSF or vitreous fluid to be effective for any results might influence antiviral treatment or chemoprophy- fungal central nervous system or ocular infection. laxis decisions for high-risk household contacts. Because the The combination of intravenous vancomycin and cef- patient lives alone, does not work in the health care environ triaxone (Option D) is recommended as empiric therapy for ment, and antiviral agents will not be initiated, the patient young, immunocompetent patients with possible community- has no indications for testing. acquired bacterial meningitis. However, this patient's Gram stain of the CSF revealed yeast, which eliminates the need for I( EY PO I TTS bacterial coverage. o Influenza testing can be considered for patients not at high risk for influenza complications if the results might influence antiviral treatment decisions. o Induction therapy for cryptococcal meningitis is lipo- o Antiviral influenza treatment can be considered for somal amphotericin B and flucfiosine; after successful adult outpatients not at high risk for complications induction therapy, fluconazole can be initiated for and illness onset no more than 2 days before presen- consolidation therapy. tation. o Aggressive reduction of intracranial pressure reduces early morbidity and mortality in patients with crypto- Bibliography coccal meningitis. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treat- ment, chemoprophylaxis, and institutional outbreak management of Bibliography seasonal influenza. Clin Infect Dis. 2019;68:el e47. [PMIO: SOSOOSOZ] Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2016;30: doi:10.1093 /cid/ciy866 77 9 20 6. [PMID : ZOegZ O 021 doi:10.1016 /j. idc. 2015. 10. 006 tr Item 38 Answer: C Ed ucationa I Objective: Treat cr5rptococcal meningitis in Item 39 Answer: A Educational Objective: Treat a patient with moderate tr a non-HIV infected patient. nonpurulent cellulitis. The most appropriate treatment for this patient is liposomal The most appropriate antibiotic therapy for this patient is amphotericin B and flucytosine (Option C). He has cryp- cefazolin (Option A). He has systemic signs of infection (fever, tococcal meningitis; stains of the cerebrospinal fluid (CSF) tachycardia, leukocytosis) indicating moderate severiSr non- show encapsulated yeast cells, characteristic of Crgptococ- purulent cellulitis of the left lower extremity. For moderate cus neoformans. Cryptococcal infection most often occurs in severity cellulitis, the Infectious Diseases Society of Amer, immunocompromised persons, such as those with HIV solid ica recommends intravenous antibiotics directed against organ transplant or stem cell transplant recipients. those tak, B-hemolytic streptococci, including penicillin, ceftriaxone, ing glucocorticoids, or those with diabetes mellitus. However, cefazolin, or clindamycin. Nonpurulent skin infections

tr Item 38 Answer: C Ed ucationa I Objective: Treat cr5rptococcal meningitis in Item 39 Answer: A Educational Objective: Treat a patient with moderate tr a non-HIV infected patient. nonpurulent cellulitis. The most appropriate treatment for this patient is liposomal The most appropriate antibiotic therapy for this patient is amphotericin B and flucytosine (Option C). He has cryp- cefazolin (Option A). He has systemic signs of infection (fever, tococcal meningitis; stains of the cerebrospinal fluid (CSF) tachycardia, leukocytosis) indicating moderate severiSr non- show encapsulated yeast cells, characteristic of Crgptococ- purulent cellulitis of the left lower extremity. For moderate cus neoformans. Cryptococcal infection most often occurs in severity cellulitis, the Infectious Diseases Society of Amer, immunocompromised persons, such as those with HIV solid ica recommends intravenous antibiotics directed against organ transplant or stem cell transplant recipients. those tak, B-hemolytic streptococci, including penicillin, ceftriaxone, ing glucocorticoids, or those with diabetes mellitus. However, cefazolin, or clindamycin. Nonpurulent skin infections 158

Answers and Critiques lll include erysipelas and cellulitis. Erysipelas refers to infection Item 40 Answer: D ff of the epidermis, upper dermis, and superflcial lymphatics. Educational Objective: Manage "hot tub" folliculitis. "''' Llsually involving the face or lower extremities, this infection is brightly erythematous with distinct, elevated borders and Observation is appropriate at this time (Option D). This associated fever, lymphangrtis, and regional lymphadenopa patient has folliculitis. Folliculitis results from inflamma- thy. Cellulitis refers to infection involving the deeper dermis tion of the hair follicles. It typically presents as perifol- and subcutaneous fat tissue. Inflammatory signs of infection licular erythematous papules and pustules over the face, are similar to erysipelas, but the area of involvement is less scalp, trunk, and thigh; however, it can appear over any well demarcated. For immunocompetent patients with cel- hair bearing area of skin. The diagnosis of folliculitis can Iulitis or erysipelas who have no systemic signs or symptoms be made from history and clinical presentation. Bacterial (i.e., mild infection), oral therapy, including penicillin VK, cultures can be performed from pustules but are usu, cephalexin, dicloxacillin, or clindamycin, directed against ally unnecessary. Skin biopsies can be performed when streptococci is recommended. causes other than bacterial infection, such as fungal or UI In addition to incision and drainage, empiric therapy herpetic infections, are suspected. This patient most likely o J

lll include erysipelas and cellulitis. Erysipelas refers to infection Item 40 Answer: D ff of the epidermis, upper dermis, and superflcial lymphatics. Educational Objective: Manage "hot tub" folliculitis. "''' Llsually involving the face or lower extremities, this infection is brightly erythematous with distinct, elevated borders and Observation is appropriate at this time (Option D). This associated fever, lymphangrtis, and regional lymphadenopa patient has folliculitis. Folliculitis results from inflamma- thy. Cellulitis refers to infection involving the deeper dermis tion of the hair follicles. It typically presents as perifol- and subcutaneous fat tissue. Inflammatory signs of infection licular erythematous papules and pustules over the face, are similar to erysipelas, but the area of involvement is less scalp, trunk, and thigh; however, it can appear over any well demarcated. For immunocompetent patients with cel- hair bearing area of skin. The diagnosis of folliculitis can Iulitis or erysipelas who have no systemic signs or symptoms be made from history and clinical presentation. Bacterial (i.e., mild infection), oral therapy, including penicillin VK, cultures can be performed from pustules but are usu, cephalexin, dicloxacillin, or clindamycin, directed against ally unnecessary. Skin biopsies can be performed when streptococci is recommended. causes other than bacterial infection, such as fungal or UI In addition to incision and drainage, empiric therapy herpetic infections, are suspected. This patient most likely o J against Staphylococcus aureus (MRSA) with doxycycline has Pseudomonas aeruginosa folliculitis, which is associ- ET P ated with the use of hot tubs, swimming pools, saunas, and .I or trimethoprim-sulfamethoxazole (Option B, C) is recom- L

against Staphylococcus aureus (MRSA) with doxycycline has Pseudomonas aeruginosa folliculitis, which is associ- ET P ated with the use of hot tubs, swimming pools, saunas, and .I or trimethoprim-sulfamethoxazole (Option B, C) is recom- L mended for moderate purulent skin infections with systemic whirlpools. It is typically self-limited, resolving within 7 to t, ?t ? signs of infection, which is not apparent in this case. 10 days. Anyone exposed to water containing P aeruginosa .E Vancomycin (Option D) provides coverage against can develop this infection, particularly in areas where the t L q, streptococci and MRSA and is recommended when non skin is in contact with water for prolonged periods of time purulent cellulitis requiring intravenous antibiotics is (i.e., under swimsuits). In addition to multiple erythem- UI = ? associated with penetrating trauma, nasal coionization or atous pruritic papulopustular or nodular lesions, patients infection with MRSA elsewhere, or injection drug use. None may also develop slight temperature elevations and mal- of these conditions is evident in this patient, so vancomycin aise. Appropriate pH and chlorine disinfectant levels can is not indicated. decrease the risk for this infection. The incubation period Necrotizing soft tissue infections, which involve subder- is usually about 2 days. mal compartments (fascia and possibly muscle) are uncom- Cephalexin (Option A), a first-generation oral mon but potentially life threatening. Necrotizing fasciitis cephalosporin, is active against gram-positive pathogens initially resembles cellulitis before potentially rapid progres- like staphylococci and streptococci and some gram-negative sion with edema, severe pain, hemorrhagic bullous lesions, Enterobacteriaceae but not P aeruginosa. skin necrosis, and local crepitus. Systemic toxicity manifests If the rash is persistent, severe, or occurs in an with fever, hypotension, tachycardia, mental status changes, immunocompromised patient, then targeted antibiotic and tachypnea. A hallmark of infection is "woody" indu- therapy against P. aeruginoso with a quinolone like cip- ration appreciated by palpation of involved subcutaneous rofloxacin (Option B) or levofloxacin can be considered. tissues. Pending culture results, empiric antibiotic treatment This patient has no indication for antibiotic treatment at includes broad-spectrum coverage for aerobic and anaero- this time. bic organisms (including MRSA) and consists of vancomy- In nonaquatic settings, Stophylococcus oureus is a cin, daptomycin, or linezolid plus piperacillin-tazobactam common cause of folliculitis. Treatment is not usually (Option E); a carbapenem; ceftriaxone plus metronidazole; indicated when only a few lesions are present because or a fluoroquinolone plus metronidazole. This patient has no these infections are usually self-limited. More extensive flndings of a necrotizing skin infection. staphylococcal folliculitis infection may require treatment with topical agents such as clindamycin or mupirocin or oral agents such as dicloxacillin or cephalexin (if sensitive o Empiric treatment of moderate severity nonpurulent to methicillin); trimethoprim sulfamethoxazole or dox- cellulitis (fever, tachycardia, leukocytosis) includes ycycline (Option C) can be used for methicillin-resistant intravenous penicillin, ceftriaxone, cefazolin, or clin- strains. damycin. . Empiric antibiotic treatment of moderate severity o "Hot tub" folliculitis is a self-limited skin infection purulent cellulitis (with systemic signs of infection) associated with the use of hot tubs, swimming pools, includes oral doxycycline or trimethoprim- saunas, and whirlpools containing Pseudomonas sulfamethoxazole. aeruginosa.

mended for moderate purulent skin infections with systemic whirlpools. It is typically self-limited, resolving within 7 to t, ?t ? signs of infection, which is not apparent in this case. 10 days. Anyone exposed to water containing P aeruginosa .E Vancomycin (Option D) provides coverage against can develop this infection, particularly in areas where the t L q, streptococci and MRSA and is recommended when non skin is in contact with water for prolonged periods of time purulent cellulitis requiring intravenous antibiotics is (i.e., under swimsuits). In addition to multiple erythem- UI = ? associated with penetrating trauma, nasal coionization or atous pruritic papulopustular or nodular lesions, patients infection with MRSA elsewhere, or injection drug use. None may also develop slight temperature elevations and mal- of these conditions is evident in this patient, so vancomycin aise. Appropriate pH and chlorine disinfectant levels can is not indicated. decrease the risk for this infection. The incubation period Necrotizing soft tissue infections, which involve subder- is usually about 2 days. mal compartments (fascia and possibly muscle) are uncom- Cephalexin (Option A), a first-generation oral mon but potentially life threatening. Necrotizing fasciitis cephalosporin, is active against gram-positive pathogens initially resembles cellulitis before potentially rapid progres- like staphylococci and streptococci and some gram-negative sion with edema, severe pain, hemorrhagic bullous lesions, Enterobacteriaceae but not P aeruginosa. skin necrosis, and local crepitus. Systemic toxicity manifests If the rash is persistent, severe, or occurs in an with fever, hypotension, tachycardia, mental status changes, immunocompromised patient, then targeted antibiotic and tachypnea. A hallmark of infection is "woody" indu- therapy against P. aeruginoso with a quinolone like cip- ration appreciated by palpation of involved subcutaneous rofloxacin (Option B) or levofloxacin can be considered. tissues. Pending culture results, empiric antibiotic treatment This patient has no indication for antibiotic treatment at includes broad-spectrum coverage for aerobic and anaero- this time. bic organisms (including MRSA) and consists of vancomy- In nonaquatic settings, Stophylococcus oureus is a cin, daptomycin, or linezolid plus piperacillin-tazobactam common cause of folliculitis. Treatment is not usually (Option E); a carbapenem; ceftriaxone plus metronidazole; indicated when only a few lesions are present because or a fluoroquinolone plus metronidazole. This patient has no these infections are usually self-limited. More extensive flndings of a necrotizing skin infection. staphylococcal folliculitis infection may require treatment with topical agents such as clindamycin or mupirocin or oral agents such as dicloxacillin or cephalexin (if sensitive o Empiric treatment of moderate severity nonpurulent to methicillin); trimethoprim sulfamethoxazole or dox- cellulitis (fever, tachycardia, leukocytosis) includes ycycline (Option C) can be used for methicillin-resistant intravenous penicillin, ceftriaxone, cefazolin, or clin- strains. damycin. . Empiric antibiotic treatment of moderate severity o "Hot tub" folliculitis is a self-limited skin infection purulent cellulitis (with systemic signs of infection) associated with the use of hot tubs, swimming pools, includes oral doxycycline or trimethoprim- saunas, and whirlpools containing Pseudomonas sulfamethoxazole. aeruginosa. Bibliography Stevens DL, Bisno AL, Chambers HFl, et al; Infectious Diseases Society of Bibliography America. Practice guidelines for the diagnosis and management of skin Hlavsa MC, Cikesh BL, Roberts VA, et al. Outbreaks associated with treated and soft tissue infections: 2014 update by the Infectious Diseases Society recreational water United States, 2000-2014. MMWR Morb Mortal Wkly of America. Clin Infect Dis. 2014;59:e1O-52. [PMtl, ZqSZSqZZ] doi:10. Rep. 2018;67(19):547-55r. IPMID: ZgZtBzz) doi:10.15585/mmwr. lO93lcidlciu444 mm6719a3

Bibliography Stevens DL, Bisno AL, Chambers HFl, et al; Infectious Diseases Society of Bibliography America. Practice guidelines for the diagnosis and management of skin Hlavsa MC, Cikesh BL, Roberts VA, et al. Outbreaks associated with treated and soft tissue infections: 2014 update by the Infectious Diseases Society recreational water United States, 2000-2014. MMWR Morb Mortal Wkly of America. Clin Infect Dis. 2014;59:e1O-52. [PMtl, ZqSZSqZZ] doi:10. Rep. 2018;67(19):547-55r. IPMID: ZgZtBzz) doi:10.15585/mmwr. lO93lcidlciu444 mm6719a3 159

Answers and Critiques Item 41 Answer: B Educational Objective: Prevent hepatitis B reactivation Item 42 Answer: D Ed ucationa I Objective: Diagnose Powassan virus tr in a patient undergoing immunosuppressive therapy. encephalitis.

Item 41 Answer: B Educational Objective: Prevent hepatitis B reactivation Item 42 Answer: D Ed ucationa I Objective: Diagnose Powassan virus tr in a patient undergoing immunosuppressive therapy. encephalitis. Entecavir is the most appropriate management of this Powassan virus infection is the most likely cause of acute patient's chronic hepatitis B virus (HBV) after transplan- encephalitis in this patient (Option D). Powassan virus is tation (Option B). She is at very high risk for hepati- transmified to humans through the bite of the Ixodes tick. tis B reactivation immediately following transplantation the same vector as Lyme disease, babesiosis. and anaplas- owing to immunosuppressive therapy to prevent rejection mosis. Unsurprisingly, most Powassan virus infections occur of the transplanted organ. Because of the high risk of reac- in regions where this tick species is plentiful. Risk is high- tivation, patients with chronic HBV infection (hepatitis est from late spring to mid fall when /,xodes ticks are most B surface antigen positivity for >6 months) who will be active. Almost all reported cases of Powassan virus pre- receiving immunosuppressive therapy, including immuno- sent with encephalitis, although this may represent a bias J UI suppression immediately after solid organ transplantation, toward testing patients with more severe disease. No specific E should begin potent antiviral therapy (entecavir or teno neurologic, laboratory or radiographic fl ndings differentiate .D rl fovir) directed against HBV. Therapy should be initiated at Powassan virus encephalitis from the many other causes of l,l o, the time of transplantation and be continued indeflnitely encephalitis. Residence in the Northeast or Middle Atlantic J CL afterward. Although this patient was likely in the immune region and seasonality might suggest the diagnosis, but other n Il control phase (normal alanine aminotransferase level, low arboviruses, including Eastern equine encephalitis virus and FT hepatitis B DNA [<zooo U/mL]), negative hepatitis e anti- West Nile virus would share these features as well. Deflni- sr gen) before transplantation and did not require therapy, tive diagnosis of Powassan virus infection requires serologic L (D UI her risk for reactivation now is high, and entecavir should testing. be started. The clinical presentations of other lxodes copatho- Without antiviral therapy, some studies have shown gens are distinct from Powassan virus infection. Fever and that the risk of HBV reactivation in kidney transplant recip- headache are common with anaplasmosis, but meningoen- ients who are hepatitis B surface antigen positive could cephalitis occurs in less than 0.5% of patients (Option A). be 50% to 94"/o. Therefore, monitoring the alanine amino- Leukopenia, thrombocytopenia, and abnormal liver transferase level alone in a high-risk situation is inadequate enzymes, also suggestive of anaplasmosis, are absent in this (Option A). patient. Symptoms of babesiosis include fever, headache, Hepatitis B vaccination and immune globulin are used myalgia, and cough (Option B). Physical examination may to prevent HBV infection in nonimmune persons (negative reveal jaundice and hepatosplenomegaly. The hallmark of surface antigen and positive surface antibody) (Option babesiosis is hemolytic anemia. Babesiosis does not cause C, D). They are unlikely to help this patient. If a patient encephalopathy, and the patient's complete blood count is undergoing pretransplant evaluation had not been vac- not compatible with this diagnosis. cinated against HBV and serology showed nonimmune Neurologic manifestations are reported in as many status, then vaccination is strongly recommended. Hepa- as 10'2, of patients with early disseminated Lyme disease titis B immune globulin is primarily used in postexposure (Option C). Facial nerve palsy is the most common neuro- prophylaxis when a susceptible person has had high-risk logic flnding, followed by meningitis, radiculopathy, other exposure to HBV. It has also been used in some liver trans- cranial nerve palsies, and mononeuritis multiplex. Enceph- plant recipients whose liver disease was related to chronic alitis or encephalomyelitis may occur as an unusual compli- hepatitis B and whose transplanted liver was from an cation of late disseminated Lyme disease, occurring months uninfected donor. to years after acute infection, but this diagnosis is excluded by the negative serologr. KEY POIITS o Patients with chronic hepatitis B infection who will KEY POIl{TS be receiving immunosuppressive therapy should . Ixodes-transmitted infections include Lyme disease, begin antiviral therapy (entecavir or tenofovir) to babesiosis, anaplasmosis, and Powassan virus prevent reactivation. encephalitis. o In patients with chronic hepatitis B infection, anti- o Residence in the Northeast or Middle Atlantic region viral therapy should be initiated at the time of and seasonality might suggest Powassan virus transplantation and be continued indefinitely encephalitis, which closely resembles other causes of afterward. encephalitis.

Entecavir is the most appropriate management of this Powassan virus infection is the most likely cause of acute patient's chronic hepatitis B virus (HBV) after transplan- encephalitis in this patient (Option D). Powassan virus is tation (Option B). She is at very high risk for hepati- transmified to humans through the bite of the Ixodes tick. tis B reactivation immediately following transplantation the same vector as Lyme disease, babesiosis. and anaplas- owing to immunosuppressive therapy to prevent rejection mosis. Unsurprisingly, most Powassan virus infections occur of the transplanted organ. Because of the high risk of reac- in regions where this tick species is plentiful. Risk is high- tivation, patients with chronic HBV infection (hepatitis est from late spring to mid fall when /,xodes ticks are most B surface antigen positivity for >6 months) who will be active. Almost all reported cases of Powassan virus pre- receiving immunosuppressive therapy, including immuno- sent with encephalitis, although this may represent a bias J UI suppression immediately after solid organ transplantation, toward testing patients with more severe disease. No specific E should begin potent antiviral therapy (entecavir or teno neurologic, laboratory or radiographic fl ndings differentiate .D rl fovir) directed against HBV. Therapy should be initiated at Powassan virus encephalitis from the many other causes of l,l o, the time of transplantation and be continued indeflnitely encephalitis. Residence in the Northeast or Middle Atlantic J CL afterward. Although this patient was likely in the immune region and seasonality might suggest the diagnosis, but other n Il control phase (normal alanine aminotransferase level, low arboviruses, including Eastern equine encephalitis virus and FT hepatitis B DNA [<zooo U/mL]), negative hepatitis e anti- West Nile virus would share these features as well. Deflni- sr gen) before transplantation and did not require therapy, tive diagnosis of Powassan virus infection requires serologic L (D UI her risk for reactivation now is high, and entecavir should testing. be started. The clinical presentations of other lxodes copatho- Without antiviral therapy, some studies have shown gens are distinct from Powassan virus infection. Fever and that the risk of HBV reactivation in kidney transplant recip- headache are common with anaplasmosis, but meningoen- ients who are hepatitis B surface antigen positive could cephalitis occurs in less than 0.5% of patients (Option A). be 50% to 94"/o. Therefore, monitoring the alanine amino- Leukopenia, thrombocytopenia, and abnormal liver transferase level alone in a high-risk situation is inadequate enzymes, also suggestive of anaplasmosis, are absent in this (Option A). patient. Symptoms of babesiosis include fever, headache, Hepatitis B vaccination and immune globulin are used myalgia, and cough (Option B). Physical examination may to prevent HBV infection in nonimmune persons (negative reveal jaundice and hepatosplenomegaly. The hallmark of surface antigen and positive surface antibody) (Option babesiosis is hemolytic anemia. Babesiosis does not cause C, D). They are unlikely to help this patient. If a patient encephalopathy, and the patient's complete blood count is undergoing pretransplant evaluation had not been vac- not compatible with this diagnosis. cinated against HBV and serology showed nonimmune Neurologic manifestations are reported in as many status, then vaccination is strongly recommended. Hepa- as 10'2, of patients with early disseminated Lyme disease titis B immune globulin is primarily used in postexposure (Option C). Facial nerve palsy is the most common neuro- prophylaxis when a susceptible person has had high-risk logic flnding, followed by meningitis, radiculopathy, other exposure to HBV. It has also been used in some liver trans- cranial nerve palsies, and mononeuritis multiplex. Enceph- plant recipients whose liver disease was related to chronic alitis or encephalomyelitis may occur as an unusual compli- hepatitis B and whose transplanted liver was from an cation of late disseminated Lyme disease, occurring months uninfected donor. to years after acute infection, but this diagnosis is excluded by the negative serologr. KEY POIITS o Patients with chronic hepatitis B infection who will KEY POIl{TS be receiving immunosuppressive therapy should . Ixodes-transmitted infections include Lyme disease, begin antiviral therapy (entecavir or tenofovir) to babesiosis, anaplasmosis, and Powassan virus prevent reactivation. encephalitis. o In patients with chronic hepatitis B infection, anti- o Residence in the Northeast or Middle Atlantic region viral therapy should be initiated at the time of and seasonality might suggest Powassan virus transplantation and be continued indefinitely encephalitis, which closely resembles other causes of afterward. encephalitis. Bibliography Bibliography Te H, Doucette K. Viral hepatitis: guidelines by the American Society of Krow-Lucal ER, Lindsey NP, Fischer M, et al. Powassan virus disease in the Transplantation Infectious Disease Community of Practice. CIin Transplant. United States, 2006-2016. Vector Borne Zoonotic Dis. 2018:18:286-290. 2019 ; 33 :e13514. [PMID' 3OBI7 047) doi: 10. 111i /ctr. 13514 IPMID : Zq 1SZOqZl doi: 10. 1089 /vb 2.2017 .2239

Bibliography Bibliography Te H, Doucette K. Viral hepatitis: guidelines by the American Society of Krow-Lucal ER, Lindsey NP, Fischer M, et al. Powassan virus disease in the Transplantation Infectious Disease Community of Practice. CIin Transplant. United States, 2006-2016. Vector Borne Zoonotic Dis. 2018:18:286-290. 2019 ; 33 :e13514. [PMID' 3OBI7 047) doi: 10. 111i /ctr. 13514 IPMID : Zq 1SZOqZl doi: 10. 1089 /vb 2.2017 .2239 160

Answers and Critiques Item 43 Answer: A Item 44 Answer: D Educational Objective: Diagnose Japanese Educational Objective: Treat recurrent genital herpes encephalitis. simplex virus infection. This patient has Japanese encephalitis (Option A). Infec Treatment with valacyclovir is most appropriate for this tion follows the bite of the Culex group of mosqui patient (Option D). She has a history of genital ulcer dis toes and is rarely symptomatic, but in patients who ease caused by herpes simplex virus type 2 (HSV 2) and has do develop clinical illness, the initial presentation is clinical flndings consistent with recurrent genital herpes, a nonspecific, febrile, viral-like illness with headache. so she should be provided with antiviral therapy. Recon Neurologic manifestations develop rapidly, encephalitis flrmation of the diagnosis in the setting of a consistent being the most common. Focal neurologic abnormal- clinical presentation is not necessary. Valacyclovir, acy ities, including paresis, cranial nerve palsies, flaccid clovir, and famciclovir are all acceptable antiviral regi- paralysis, and parkinsonian-like movement disorders, mens for management of recurrent genital HSV and will UI frequently accompany the encephalopathic state. Some shorten the duration of this episode. Antiviral therapy for o J patients become comatose. Japanese encephalitis may recurrent infection is recommended within 1 day of lesion .g P also present as mild, febrile, aseptic meningitis. Tha onset or at the onset of prodromal symptoms. Regardless a- L rJ lamic lesions seen on MRI scans are typical; diagnosis of the antiviral agent used, treatment regimens for recur- is confirmed by early detection of IgM antibodies in the rent genital HSV are short (Z-S days). The patient should =, s - atr cerebrospinal fluid, and later in the serum. Although the be counseled that she may experience subsequent recur- UI L (u virus is endemic throughout most of Asia and portions rences, and she can be provided with a prescription for of the Western Pacific, the incidence of infection is low antiviral therapy to begin immediately if she experiences ta = E in travelers to these areas. A vaccine is available that can another recurrence. Long-term suppressive therapy is an produce effective immunity. option if she experiences frequent subsequent recurrences The intracellular bacterium Orientia tsutsugamushi or if she desires to reduce the potential for transmission causes scrub typhus (Option B). Humans acquire the dis- to a future sexual partner who does not have HSV-2 infec- ease through the bite of the larval stage of mites known tion. She should be counseled regarding the importance of as chiggers. It is predominantly present in Asia, although informing future sexual partners of her diagnosis and the infection can also occur in parts of Europe, Africa, and South potential for viral shedding and transmission even without America. A black eschar is often present at the site of inocu- active lesions. HSV-2 seropositive persons are at increased lation; this is followed by fever, rash, and various multiorgan risk for HIV acquisition, so the importance of condoms system symptoms. Central nervous system complications are should be stressed. infrequent. Benzathine penicillin (Option A) is used to treat genital Tick borne encephalitis (Option C) is a flavivirus infec- ulcer disease caused by Treponema pallidum. Syphilitic tion spread by members of the lxodes species of ticks, which, chancres generally present as single, not multiple, lesions, along with rodents, function as viral reservoirs. Character- and they are usually painless. Chancres are a manifestation istically, clinical infection manifests in a biphasic manner, of primary syphilis, but this patient has not been sexually beginning with a febrile viral-like illness, a brief period active for a year, so this diagnosis would be unlikely. of defervescence, and one or more neurologic syndromes. Nucleic acid ampliflcation testing (Option B) is rec- The lack of a biphasic illness makes tick-borne encephalitis ommended to conflrm genital HSV infection in persons unlikely in this patient. who present with initial genital ulcer disease. It would not Aedes aegyptimosquitoes spread the yellow fever virus be indicated in this patient, who was previously diagnosed (Option D) to humans, either from nonhuman primates with HSV. (jungle or sylvatic yellow fever) or by person-to-person Type-speciflc serologic testing (Option C) is not advised spread (urban yellow fever). Fever, headache, myalgia, nau- for diagnosing symptomatic ulcer disease because patients sea, and vomiting are common symptoms in those who can be seropositive for HSV-1 or HSV-2 yet have genital ulcers become symptomatic, some of whom may progress to severe from another cause. multisystem disease manifested by jaundice, kidney injury KEY POI l{T and hemorrhagic shock. . Treatment with valacyclovir, acyclovir, or famciclovir KEY POITT is appropriate for patients with a history of genital . Symptomatic Japanese encephalitis typically manifests ulcer disease caused by herpes simplex virus Upe 2 as a nonspecific febrile, viral-like illness quickly followed and clinical findings consistent with recurrent genital by an encephalopathic state. herpes.

Item 43 Answer: A Item 44 Answer: D Educational Objective: Diagnose Japanese Educational Objective: Treat recurrent genital herpes encephalitis. simplex virus infection. This patient has Japanese encephalitis (Option A). Infec Treatment with valacyclovir is most appropriate for this tion follows the bite of the Culex group of mosqui patient (Option D). She has a history of genital ulcer dis toes and is rarely symptomatic, but in patients who ease caused by herpes simplex virus type 2 (HSV 2) and has do develop clinical illness, the initial presentation is clinical flndings consistent with recurrent genital herpes, a nonspecific, febrile, viral-like illness with headache. so she should be provided with antiviral therapy. Recon Neurologic manifestations develop rapidly, encephalitis flrmation of the diagnosis in the setting of a consistent being the most common. Focal neurologic abnormal- clinical presentation is not necessary. Valacyclovir, acy ities, including paresis, cranial nerve palsies, flaccid clovir, and famciclovir are all acceptable antiviral regi- paralysis, and parkinsonian-like movement disorders, mens for management of recurrent genital HSV and will UI frequently accompany the encephalopathic state. Some shorten the duration of this episode. Antiviral therapy for o J patients become comatose. Japanese encephalitis may recurrent infection is recommended within 1 day of lesion .g P also present as mild, febrile, aseptic meningitis. Tha onset or at the onset of prodromal symptoms. Regardless a- L rJ lamic lesions seen on MRI scans are typical; diagnosis of the antiviral agent used, treatment regimens for recur- is confirmed by early detection of IgM antibodies in the rent genital HSV are short (Z-S days). The patient should =, s - atr cerebrospinal fluid, and later in the serum. Although the be counseled that she may experience subsequent recur- UI L (u virus is endemic throughout most of Asia and portions rences, and she can be provided with a prescription for of the Western Pacific, the incidence of infection is low antiviral therapy to begin immediately if she experiences ta = E in travelers to these areas. A vaccine is available that can another recurrence. Long-term suppressive therapy is an produce effective immunity. option if she experiences frequent subsequent recurrences The intracellular bacterium Orientia tsutsugamushi or if she desires to reduce the potential for transmission causes scrub typhus (Option B). Humans acquire the dis- to a future sexual partner who does not have HSV-2 infec- ease through the bite of the larval stage of mites known tion. She should be counseled regarding the importance of as chiggers. It is predominantly present in Asia, although informing future sexual partners of her diagnosis and the infection can also occur in parts of Europe, Africa, and South potential for viral shedding and transmission even without America. A black eschar is often present at the site of inocu- active lesions. HSV-2 seropositive persons are at increased lation; this is followed by fever, rash, and various multiorgan risk for HIV acquisition, so the importance of condoms system symptoms. Central nervous system complications are should be stressed. infrequent. Benzathine penicillin (Option A) is used to treat genital Tick borne encephalitis (Option C) is a flavivirus infec- ulcer disease caused by Treponema pallidum. Syphilitic tion spread by members of the lxodes species of ticks, which, chancres generally present as single, not multiple, lesions, along with rodents, function as viral reservoirs. Character- and they are usually painless. Chancres are a manifestation istically, clinical infection manifests in a biphasic manner, of primary syphilis, but this patient has not been sexually beginning with a febrile viral-like illness, a brief period active for a year, so this diagnosis would be unlikely. of defervescence, and one or more neurologic syndromes. Nucleic acid ampliflcation testing (Option B) is rec- The lack of a biphasic illness makes tick-borne encephalitis ommended to conflrm genital HSV infection in persons unlikely in this patient. who present with initial genital ulcer disease. It would not Aedes aegyptimosquitoes spread the yellow fever virus be indicated in this patient, who was previously diagnosed (Option D) to humans, either from nonhuman primates with HSV. (jungle or sylvatic yellow fever) or by person-to-person Type-speciflc serologic testing (Option C) is not advised spread (urban yellow fever). Fever, headache, myalgia, nau- for diagnosing symptomatic ulcer disease because patients sea, and vomiting are common symptoms in those who can be seropositive for HSV-1 or HSV-2 yet have genital ulcers become symptomatic, some of whom may progress to severe from another cause. multisystem disease manifested by jaundice, kidney injury KEY POI l{T and hemorrhagic shock. . Treatment with valacyclovir, acyclovir, or famciclovir KEY POITT is appropriate for patients with a history of genital . Symptomatic Japanese encephalitis typically manifests ulcer disease caused by herpes simplex virus Upe 2 as a nonspecific febrile, viral-like illness quickly followed and clinical findings consistent with recurrent genital by an encephalopathic state. herpes. Bibliography Bibliography Pavli A, Maltezou HC. Travel-acquired Japanese encephalitis and vaccination considerations. J Infect Dev Ctries. 2015;9(9):917-924. [PMID: z1+oszst] Gnann IW lr, Whitley RJ. Clinical practice. Genital herpes. N Engl J Med doi:10.3855 /jidc.5108 2Ot6 37 5 :666-Z+. [plvtlp' zt SSZASZ] doi:10.1056/ NEJMcp1603178

Bibliography Bibliography Pavli A, Maltezou HC. Travel-acquired Japanese encephalitis and vaccination considerations. J Infect Dev Ctries. 2015;9(9):917-924. [PMID: z1+oszst] Gnann IW lr, Whitley RJ. Clinical practice. Genital herpes. N Engl J Med doi:10.3855 /jidc.5108 2Ot6 37 5 :666-Z+. [plvtlp' zt SSZASZ] doi:10.1056/ NEJMcp1603178 161

Answers and Critiques Item 45 Answer: B tr Ed ucati o n a I O bj ective : Prevent transmission of varicella- Bibliography Siegel JD. Rhinehart E, Jackson M, Chiarello L, the Healthcare Infection Control Practices Advisory Committee. 2007 Guideline for isolation zoster virus. precautions: Preventing transmission of infectious agents in healthcare settings. Last update: luly 2019. Available at https://www.cdc.gov/infec- Airborne and contact precautions are necessary for this tioncontrol/guidelines/isolation/index.html. Accessed November 9, 2019' patient (Option B). She is immunocompromised and has herpes zoster ir-rfection, which is caused by the varicella- zoster virus (VZV). In imrnunocompetent persons. dis- Item 45 Answer: A seminated herpes zoster is deflned as involvement of more Educational Objective: Manage a patient with influenza. than two dermatomes or vesicular lesions that cross the The most appropriate management is to obtain influenza midline. In immunocompromised persons. the risk for dis- polymerase chain reaction (PCR) testing and start influenza sernination is increased. thus any dermatomal involvement treatment as soon as possible (Option A). Infectious Diseases D is considered disseminated zoster. Disseminated herpes Society of America (IDSA) guidelines recommend initiating J UI zoster inf'ectior-r includes a risk of VZV dissemination to antiviral treatment as soon as possible for adults with docu € the respiratory tractl transmission to nonimmune health tD rl mented or suspected influenza who are hospitalized and for t^ care personnel or other patients (no history of naturally q, outpatients with severe or progressive illness regardless of acquired chickenpox or unvaccinated) can then occur - a by direct contact r,vith vesicles or by small (<5 microns) illness duration. Treatment should also be initiated as soon as n airborne respiratory droplets. Patients with disseminated possible for all other patients at high risk for influenza-related t=. complications such as older adults and immunosuppressed zoster should be cared for using contact (gloves and gown lt-a persons, such as this patient. Treatment can also be con- E for all contact) and airborne (an airborne infection isola .D sidered for otherwise healthy outpatients if started within UI tion room, also referred to as a negative pressure room) 48 hours, household contacts of severely immunosuppressed precautions; health care personnel should also wear fit- patients, and health care workers who care for patients at high tested N95 respirators. risk of developing complications from influenza. Neuramin Airborne precautions alone (Option A), without con idase inhibitors have activity against influenza A and B. They tact precautions, would not provide protection fiom clirect can be given orally (oseltamivir), intranasally (zanamivir), or contact with herpes zoster lesions, which are inf'ectious until intravenously (peramivir). Baloxavir is a polymerase acidic they are dry and crusted over. endonuclease inhibitor that can be given as single-dose ther Active herpes zoster lesions are inf'ectious through apy for uncomplicated influenza. It must be started within direct contact with vesicular fluid. The rash develops in 48 hours of symptom onset and appears to be as eflective as a clusters of vesicles. New vesicles continue to form over 3 S-day course of oseltamivir. to 5 clays and progressively dry and crust over. Whenever The serologic diagnosis of seasonal influenza virus possible, lesions sl-rould be covered. and nonimmune per- infection requires paired acute and convalescent serum sons should not have direct contact r.r,ith active vesicular specimens that must be collected and tested together and lesior-rs. In ir-nrnunocompetent patients, contact precau- cannot inform clinical management. No validated IgM assay tions alone (Option C) would be appropriate with only one exists to diagnose seasonal influenza virus infection in a involved dermatome. However, this patient is immuno single serum specimen (Option B). compromised. and therefbre requires contact and airborne Influenza PCR is recommended over rapid antigen tests precautions. (Option C). Rapid antigen tests of respiratory samples from Droplet precautions provide protection only from large nasopharyngeal swabs can detect influenza A and B, but their droplet nuclei (>5 n-ricrons). For droplet precautions. health sensitivity ranges from 59% Io 93%. Detection of viral nucleic care personnel should wear face or surgical masks when acid by PCR is rapid, has high sensitivity and specificity, and within 3 f'eet of'the patient. Small droplet nuclei, as with can determine the type and subtype of influenza virus. disseminated herpes zoster infection. can be airborne and The IDSA recommends that clinicians not use viral cul- travel nruch larger distances on air currents. Droplet precau ture (Option D) for initial or primary diagnosis of influenza tions :ilone or droplet precautions and contact precautions because results will not be available in a timely manner to combir-red (Option D, E) is not sufficient to protect against inform clinical management. airborne spread of'the virus. KEY POI lIIS t(EY P0tilTS o Influenza polymerase chain reaction testing is recom- o Disseminated herpes zoster is diagnosed in immuno- mended over rapid influenza antigen tests. compromised patients when only one dermatome is o Antiviral treatment is recommended as soon as possible involved. for adults with documented or suspected influenza o Because disseminated herpes zoster may involve the who are hospitalized, for outpatients with severe or respiratory tract, contact and airborne precautions are progressive illness regardless of illness duration, and necessary to prevent the spread ofdisease. for older adults and immunosuppressed patients.

Item 45 Answer: B tr Ed ucati o n a I O bj ective : Prevent transmission of varicella- Bibliography Siegel JD. Rhinehart E, Jackson M, Chiarello L, the Healthcare Infection Control Practices Advisory Committee. 2007 Guideline for isolation zoster virus. precautions: Preventing transmission of infectious agents in healthcare settings. Last update: luly 2019. Available at https://www.cdc.gov/infec- Airborne and contact precautions are necessary for this tioncontrol/guidelines/isolation/index.html. Accessed November 9, 2019' patient (Option B). She is immunocompromised and has herpes zoster ir-rfection, which is caused by the varicella- zoster virus (VZV). In imrnunocompetent persons. dis- Item 45 Answer: A seminated herpes zoster is deflned as involvement of more Educational Objective: Manage a patient with influenza. than two dermatomes or vesicular lesions that cross the The most appropriate management is to obtain influenza midline. In immunocompromised persons. the risk for dis- polymerase chain reaction (PCR) testing and start influenza sernination is increased. thus any dermatomal involvement treatment as soon as possible (Option A). Infectious Diseases D is considered disseminated zoster. Disseminated herpes Society of America (IDSA) guidelines recommend initiating J UI zoster inf'ectior-r includes a risk of VZV dissemination to antiviral treatment as soon as possible for adults with docu € the respiratory tractl transmission to nonimmune health tD rl mented or suspected influenza who are hospitalized and for t^ care personnel or other patients (no history of naturally q, outpatients with severe or progressive illness regardless of acquired chickenpox or unvaccinated) can then occur - a by direct contact r,vith vesicles or by small (<5 microns) illness duration. Treatment should also be initiated as soon as n airborne respiratory droplets. Patients with disseminated possible for all other patients at high risk for influenza-related t=. complications such as older adults and immunosuppressed zoster should be cared for using contact (gloves and gown lt-a persons, such as this patient. Treatment can also be con- E for all contact) and airborne (an airborne infection isola .D sidered for otherwise healthy outpatients if started within UI tion room, also referred to as a negative pressure room) 48 hours, household contacts of severely immunosuppressed precautions; health care personnel should also wear fit- patients, and health care workers who care for patients at high tested N95 respirators. risk of developing complications from influenza. Neuramin Airborne precautions alone (Option A), without con idase inhibitors have activity against influenza A and B. They tact precautions, would not provide protection fiom clirect can be given orally (oseltamivir), intranasally (zanamivir), or contact with herpes zoster lesions, which are inf'ectious until intravenously (peramivir). Baloxavir is a polymerase acidic they are dry and crusted over. endonuclease inhibitor that can be given as single-dose ther Active herpes zoster lesions are inf'ectious through apy for uncomplicated influenza. It must be started within direct contact with vesicular fluid. The rash develops in 48 hours of symptom onset and appears to be as eflective as a clusters of vesicles. New vesicles continue to form over 3 S-day course of oseltamivir. to 5 clays and progressively dry and crust over. Whenever The serologic diagnosis of seasonal influenza virus possible, lesions sl-rould be covered. and nonimmune per- infection requires paired acute and convalescent serum sons should not have direct contact r.r,ith active vesicular specimens that must be collected and tested together and lesior-rs. In ir-nrnunocompetent patients, contact precau- cannot inform clinical management. No validated IgM assay tions alone (Option C) would be appropriate with only one exists to diagnose seasonal influenza virus infection in a involved dermatome. However, this patient is immuno single serum specimen (Option B). compromised. and therefbre requires contact and airborne Influenza PCR is recommended over rapid antigen tests precautions. (Option C). Rapid antigen tests of respiratory samples from Droplet precautions provide protection only from large nasopharyngeal swabs can detect influenza A and B, but their droplet nuclei (>5 n-ricrons). For droplet precautions. health sensitivity ranges from 59% Io 93%. Detection of viral nucleic care personnel should wear face or surgical masks when acid by PCR is rapid, has high sensitivity and specificity, and within 3 f'eet of'the patient. Small droplet nuclei, as with can determine the type and subtype of influenza virus. disseminated herpes zoster infection. can be airborne and The IDSA recommends that clinicians not use viral cul- travel nruch larger distances on air currents. Droplet precau ture (Option D) for initial or primary diagnosis of influenza tions :ilone or droplet precautions and contact precautions because results will not be available in a timely manner to combir-red (Option D, E) is not sufficient to protect against inform clinical management. airborne spread of'the virus. KEY POI lIIS t(EY P0tilTS o Influenza polymerase chain reaction testing is recom- o Disseminated herpes zoster is diagnosed in immuno- mended over rapid influenza antigen tests. compromised patients when only one dermatome is o Antiviral treatment is recommended as soon as possible involved. for adults with documented or suspected influenza o Because disseminated herpes zoster may involve the who are hospitalized, for outpatients with severe or respiratory tract, contact and airborne precautions are progressive illness regardless of illness duration, and necessary to prevent the spread ofdisease. for older adults and immunosuppressed patients. 162

Answers and Critiques Bibliography Bibliography Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Muller DA, Depelsenaire AC, Young pR. Clinical and laboratory diagnosis of Infectious Diseases Society of America: 201g update on diagnosis, treat dengue virus infecrion. J Infect Dis. 2017;215:S89-S95. [pMiD, Ze+OZqql ment, chemoprophylaxis, and institutional outbreak management of doi: 10.1093/infdis/jiw649 seasonal influenza. Clin Infect Dis. 2019;68:et_e47. [pMID: SOsOOSOz] doi:10.1093 /cid/ciy866

Bibliography Bibliography Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Muller DA, Depelsenaire AC, Young pR. Clinical and laboratory diagnosis of Infectious Diseases Society of America: 201g update on diagnosis, treat dengue virus infecrion. J Infect Dis. 2017;215:S89-S95. [pMiD, Ze+OZqql ment, chemoprophylaxis, and institutional outbreak management of doi: 10.1093/infdis/jiw649 seasonal influenza. Clin Infect Dis. 2019;68:et_e47. [pMID: SOsOOSOz] doi:10.1093 /cid/ciy866 Item 48 Item 47 Answer: B Answer: B Educational Objective: Treat bacterial meningitis tr Educational Objective: Diagnose dengue virus infection. empirically. This man has a typical presentation of dengue virus infec- Empiric antibiotic therapy r.t,ith vancomycin, ampicillin, tion (Option B). This flavivirus is endemic in South and ceftriaxone, and dexamethasone is most appropriate fbr Central America (and the Caribbean, the paciflc Islands, this patient (Option B). He has a classic presentation of Southeast Asia, and parts of Africa). It is transmitted by the community-acquired bacterial meningitis. Patients typi- UI q, Aedes mosquito species and is the most common cause of cally have an acute presentation with f'ever. l-readache, stiff' J ET fever in travelers returning from South America. Incubation neck. and altered mental status. The cerebrospinal fluid a- P a-

Item 48 Item 47 Answer: B Answer: B Educational Objective: Treat bacterial meningitis tr Educational Objective: Diagnose dengue virus infection. empirically. This man has a typical presentation of dengue virus infec- Empiric antibiotic therapy r.t,ith vancomycin, ampicillin, tion (Option B). This flavivirus is endemic in South and ceftriaxone, and dexamethasone is most appropriate fbr Central America (and the Caribbean, the paciflc Islands, this patient (Option B). He has a classic presentation of Southeast Asia, and parts of Africa). It is transmitted by the community-acquired bacterial meningitis. Patients typi- UI q, Aedes mosquito species and is the most common cause of cally have an acute presentation with f'ever. l-readache, stiff' J ET fever in travelers returning from South America. Incubation neck. and altered mental status. The cerebrospinal fluid a- P a- (CSF) proflle shons neutrophilic pleocytosis (leukocytes L ranges from a few days to 2 weeks, after which symptom- L' atic illness manifests with the abrupt onset of high fever, >1000iprl I1OOO x t06rll in tr.to thirds of patients), an EF headache, retro-orbital pain, myalgia, arthralgia, and lower elevated protein level (median in bacterial n-reningitis is .E UI back pain. The development of petechiae after deflating a 390 mgidl [3900 mgrll), and severe hypoglycorrhachia; L a, blood pressure cuff (positive tourniquet test) is character- a high serum leukocyte count is also typical. The most UI istic. Fever usually abates after a few days and then mildly common cause of bacterial meningitis is Sfreptococcus -= returns (saddleback pattern), frequently accompanied by a pneuntonioe; sinusitis or otitis media is a clue. In countries maculopapular rash. Leukopenia, thrombocytopenia, and such as the United States n,ith a prevalence of greater than elevated hepatic aminotransferase levels are frequent lab- 7"1, of ceftriaxone-resistant pneumococcus, a combination

(CSF) proflle shons neutrophilic pleocytosis (leukocytes L ranges from a few days to 2 weeks, after which symptom- L' atic illness manifests with the abrupt onset of high fever, >1000iprl I1OOO x t06rll in tr.to thirds of patients), an EF headache, retro-orbital pain, myalgia, arthralgia, and lower elevated protein level (median in bacterial n-reningitis is .E UI back pain. The development of petechiae after deflating a 390 mgidl [3900 mgrll), and severe hypoglycorrhachia; L a, blood pressure cuff (positive tourniquet test) is character- a high serum leukocyte count is also typical. The most UI istic. Fever usually abates after a few days and then mildly common cause of bacterial meningitis is Sfreptococcus -= returns (saddleback pattern), frequently accompanied by a pneuntonioe; sinusitis or otitis media is a clue. In countries maculopapular rash. Leukopenia, thrombocytopenia, and such as the United States n,ith a prevalence of greater than elevated hepatic aminotransferase levels are frequent lab- 7"1, of ceftriaxone-resistant pneumococcus, a combination oratory flndings. of vancomycin and ceftriaxone (Option C) is recommended Chikungunya (Option A) is also spread by the bite of the pendir-rg susceptibility results of the isolate; the addition of Aedes mosquito. Symptomatic infection is uncommon, but ampicillin is recommended in immunosuppressed persons disease signs and symptoms closely mimic those of dengue and patients older than 50 years to provide coverage fbr fever. However, severe joint pain, often involving the hands possible Listeria ntonocytogenes (Option A). Adjunctive and feet, and relapsing arthralgia/arthritis are distinguishing dexamethasone. given concomitantly with the flrst dose features. of antibiotic therapy; reduces morbidity and mortality in Leptospirosis (Option C) is caused by a spirochetal bac- adults with pneumococcal meningitis in developed coun- terium excreted in the urine of infected animals, mainly tries. In patients with a known cause of bacterial menin- rodents. Human illness occurs after direct contact with gitis, dexamethasone treatnlent should be limited to those rodent urine or the ingestion of contaminated food or water. r.t ith S. pneumonioe rneningitis. Dexamethasone should

oratory flndings. of vancomycin and ceftriaxone (Option C) is recommended Chikungunya (Option A) is also spread by the bite of the pendir-rg susceptibility results of the isolate; the addition of Aedes mosquito. Symptomatic infection is uncommon, but ampicillin is recommended in immunosuppressed persons disease signs and symptoms closely mimic those of dengue and patients older than 50 years to provide coverage fbr fever. However, severe joint pain, often involving the hands possible Listeria ntonocytogenes (Option A). Adjunctive and feet, and relapsing arthralgia/arthritis are distinguishing dexamethasone. given concomitantly with the flrst dose features. of antibiotic therapy; reduces morbidity and mortality in Leptospirosis (Option C) is caused by a spirochetal bac- adults with pneumococcal meningitis in developed coun- terium excreted in the urine of infected animals, mainly tries. In patients with a known cause of bacterial menin- rodents. Human illness occurs after direct contact with gitis, dexamethasone treatnlent should be limited to those rodent urine or the ingestion of contaminated food or water. r.t ith S. pneumonioe rneningitis. Dexamethasone should The clinical presentation ranges from a self-limited biphasic be discontinued promptly if the cause is not S. pneumo- febrile illness to a more severe form of infection, known as trioe because it provides no added benefit in inf'ection with Weil disease. Liver, kidney, pulmonary or multisystem fail- other meningeal pathogens and can increase mortality if' ure may occur. Conjunctival erythema and pain in the lower the patient has L. tnonocatogenes. back and calf muscles are characteristic. Vancomycin and cef'epime (or ceftazidime or mero- Most typhoid fever (Option D) diagnosed in the United penem) (Option D) are indicated in patier-rts r,vith health States occurs in persons who have recently traveled to South care-associated r,entriculitis and meningitis to proriide cov- and Southeast Asia. The incubation period is 1 to 2 weeks, erage fbr possible Pseudornonas aeruginosa and Sfophy- and fever presents more slowly and is more progressive and lococclrs eure us or Staphylococcus epiderntidis. Acyclovir longer lasting than in arbovirus infections. Gastrointestinal is not indicated because the clinical presentation and CSF symptoms are common, ranging from diarrhea to constipa- proflle are not consistent with herpes sirnplex encephalitis. tion. A delayed rash arises on the chest or abdomen in about I(EY POIilT5 20% of patients. . Empiric therapy for bacterial meningitis should l(EY P0r1{TS include vancomycin, ceftriaxone, and ampicillin in . Dengue virus infection is the most common cause of adult patients older than 50 years. fever in travelers returning from South America. . Adjunctive dexamethasone is given concomitantly o Dengue infection manifests with the abrupt onset of with the first dose of empiric antibiotic therapy high fever, headache, retro-orbital pain, myalgia, for bacterial meningitis but should be discontinued arthralgia, and lower back pain (break-bone fever); a promptly if the cause is not Streptococcus positive tourniquet test is characteristic. pneumoniae.

The clinical presentation ranges from a self-limited biphasic be discontinued promptly if the cause is not S. pneumo- febrile illness to a more severe form of infection, known as trioe because it provides no added benefit in inf'ection with Weil disease. Liver, kidney, pulmonary or multisystem fail- other meningeal pathogens and can increase mortality if' ure may occur. Conjunctival erythema and pain in the lower the patient has L. tnonocatogenes. back and calf muscles are characteristic. Vancomycin and cef'epime (or ceftazidime or mero- Most typhoid fever (Option D) diagnosed in the United penem) (Option D) are indicated in patier-rts r,vith health States occurs in persons who have recently traveled to South care-associated r,entriculitis and meningitis to proriide cov- and Southeast Asia. The incubation period is 1 to 2 weeks, erage fbr possible Pseudornonas aeruginosa and Sfophy- and fever presents more slowly and is more progressive and lococclrs eure us or Staphylococcus epiderntidis. Acyclovir longer lasting than in arbovirus infections. Gastrointestinal is not indicated because the clinical presentation and CSF symptoms are common, ranging from diarrhea to constipa- proflle are not consistent with herpes sirnplex encephalitis. tion. A delayed rash arises on the chest or abdomen in about I(EY POIilT5 20% of patients. . Empiric therapy for bacterial meningitis should l(EY P0r1{TS include vancomycin, ceftriaxone, and ampicillin in . Dengue virus infection is the most common cause of adult patients older than 50 years. fever in travelers returning from South America. . Adjunctive dexamethasone is given concomitantly o Dengue infection manifests with the abrupt onset of with the first dose of empiric antibiotic therapy high fever, headache, retro-orbital pain, myalgia, for bacterial meningitis but should be discontinued arthralgia, and lower back pain (break-bone fever); a promptly if the cause is not Streptococcus positive tourniquet test is characteristic. pneumoniae. 163

Answers and Critiques bullae are the classic cutaneous manifestation' Infection XEY POITIS usually occurs after consumption of raw shellfish such as o The presence of extended-spectrum B-lactamase oysters or skin trauma incurred in warm sea water or brack- (ESBL)-producing Escherichia coliis suggested by the ish waters where the organism thrives. antibiotic susceptibilis pattern demonstrating resist- I( EY PO I T{T ance to oxyimino-B-lactam substrates (e'g', cefotaxime' o Life-threatening infection with CopnocAtophoga can- ceftazidime, ceftriaxone, cefepime)' imorsus typically occurs after a dog (or cat) bite or . Carbapenems (imipenem, meropenem, doripenem, scratch or exposure to dog saliva in patients with ertapenem) are the preferred agents for treating infec- asplenia, hyposplenism, history of excessive alcohol tions with extended-spectrum B-lactamase-producing use, or cirrhosis. organisms.

imorsus typically occurs after a dog (or cat) bite or . Carbapenems (imipenem, meropenem, doripenem, scratch or exposure to dog saliva in patients with ertapenem) are the preferred agents for treating infec- asplenia, hyposplenism, history of excessive alcohol tions with extended-spectrum B-lactamase-producing use, or cirrhosis. organisms. D Bibliography Bibliography ) UI Butler T. Capnocyophaga canitnorsus: an emerging cause of sepsis. meningitis' Pana ZD, Zaoutis T. Treatment of extended-spectrum 13 lactamase-produc- { ancl posi spteneitomy int'ection after dog bites. Eur J Clin Microbiol Inf'ect ing Enterobacteriaceae (ESBLs) infections: what have we learned until .D rl Dis. 2015r34:1 271 BO. [PMID: 25828064] doi:10. 1007is10096-015-2360-7 no*? f'tooOR.s. 2018;7. [PMtO, gOzzseOs] doi:10.12688ifl O0oresearch' ul t4822.1 o, J EL Item 53 Answer: C a-l *- -a tr Ed ucationa I Objective : Treat a multidrug-resistant Item 54 Answer: A st infection. Educational Obiective: Treat severe malaria. E .D U) Ertapenem is tl-re most appropriate treatment (Option C). Intravenous artesunate is the most appropriate treatment for 'lhis patient has pyelonephritis caused by extended spectntm this patient (Option A). He has severe Plasmodium falci- B lactamase (ESBL)-producing Eschericltia cc:li suggested by parum malaria that is likely mefloquine resistant, which is the antibiotic susceptibility pattern demonstrating resistance becoming increasingly prevalent in various parts of South- to ox.virnino p-lactam substrates (e.g., cefotaxime, ceftazi- east Asia, including Laos and Cambodia. On the peripheral dime. ceftriaxone). l-aboratory identification of ESBl,s is dif- blood smear, thin, often multiple rings on the inner surface ficult because they are a heterogeneous group of enzymes. of young and old erythrocy'tes, as well as banana-shaped HSBL producing gram negative organisms are capable clf gametocytes, are distinctive morphologic characteristics of hydrolyzing higher generation cephalosporins that have an P. falciparum species. Severe malaria primarily occurs with

D Bibliography Bibliography ) UI Butler T. Capnocyophaga canitnorsus: an emerging cause of sepsis. meningitis' Pana ZD, Zaoutis T. Treatment of extended-spectrum 13 lactamase-produc- { ancl posi spteneitomy int'ection after dog bites. Eur J Clin Microbiol Inf'ect ing Enterobacteriaceae (ESBLs) infections: what have we learned until .D rl Dis. 2015r34:1 271 BO. [PMID: 25828064] doi:10. 1007is10096-015-2360-7 no*? f'tooOR.s. 2018;7. [PMtO, gOzzseOs] doi:10.12688ifl O0oresearch' ul t4822.1 o, J EL Item 53 Answer: C a-l *- -a tr Ed ucationa I Objective : Treat a multidrug-resistant Item 54 Answer: A st infection. Educational Obiective: Treat severe malaria. E .D U) Ertapenem is tl-re most appropriate treatment (Option C). Intravenous artesunate is the most appropriate treatment for 'lhis patient has pyelonephritis caused by extended spectntm this patient (Option A). He has severe Plasmodium falci- B lactamase (ESBL)-producing Eschericltia cc:li suggested by parum malaria that is likely mefloquine resistant, which is the antibiotic susceptibility pattern demonstrating resistance becoming increasingly prevalent in various parts of South- to ox.virnino p-lactam substrates (e.g., cefotaxime, ceftazi- east Asia, including Laos and Cambodia. On the peripheral dime. ceftriaxone). l-aboratory identification of ESBl,s is dif- blood smear, thin, often multiple rings on the inner surface ficult because they are a heterogeneous group of enzymes. of young and old erythrocy'tes, as well as banana-shaped HSBL producing gram negative organisms are capable clf gametocytes, are distinctive morphologic characteristics of hydrolyzing higher generation cephalosporins that have an P. falciparum species. Severe malaria primarily occurs with oxyimino side chain such as cefbtaxime. ceftazidime, ceftriax- P. J'alciparum and is deflned by a high degree of parasitemia

D Bibliography Bibliography ) UI Butler T. Capnocyophaga canitnorsus: an emerging cause of sepsis. meningitis' Pana ZD, Zaoutis T. Treatment of extended-spectrum 13 lactamase-produc- { ancl posi spteneitomy int'ection after dog bites. Eur J Clin Microbiol Inf'ect ing Enterobacteriaceae (ESBLs) infections: what have we learned until .D rl Dis. 2015r34:1 271 BO. [PMID: 25828064] doi:10. 1007is10096-015-2360-7 no*? f'tooOR.s. 2018;7. [PMtO, gOzzseOs] doi:10.12688ifl O0oresearch' ul t4822.1 o, J EL Item 53 Answer: C a-l *- -a tr Ed ucationa I Objective : Treat a multidrug-resistant Item 54 Answer: A st infection. Educational Obiective: Treat severe malaria. E .D U) Ertapenem is tl-re most appropriate treatment (Option C). Intravenous artesunate is the most appropriate treatment for 'lhis patient has pyelonephritis caused by extended spectntm this patient (Option A). He has severe Plasmodium falci- B lactamase (ESBL)-producing Eschericltia cc:li suggested by parum malaria that is likely mefloquine resistant, which is the antibiotic susceptibility pattern demonstrating resistance becoming increasingly prevalent in various parts of South- to ox.virnino p-lactam substrates (e.g., cefotaxime, ceftazi- east Asia, including Laos and Cambodia. On the peripheral dime. ceftriaxone). l-aboratory identification of ESBl,s is dif- blood smear, thin, often multiple rings on the inner surface ficult because they are a heterogeneous group of enzymes. of young and old erythrocy'tes, as well as banana-shaped HSBL producing gram negative organisms are capable clf gametocytes, are distinctive morphologic characteristics of hydrolyzing higher generation cephalosporins that have an P. falciparum species. Severe malaria primarily occurs with oxyimino side chain such as cefbtaxime. ceftazidime, ceftriax- P. J'alciparum and is deflned by a high degree of parasitemia one. and cefepime. The carbapenem class of antibiotics (imi- (>10'/,) accompanied by one or more clinical (e.g., pulmonary penem, meropenem. doripenetri. ertapenem) is the preferred edema, seizures and confusion, bleeding, jaundice, shock) group of agents for treating inf'ections rvitl-r ESBl-producing and laboratory (e.g., severe anemia, kidney injury metabolic organisms. Ertapenem has an advantage over the other acidosis, hypoglycemia, hemoglobinuria) criteria. The spleen carbapenems rt ith once-daily oral dosing, but some ESBL- functions to fllter and clear malaria-infected erythrocytes, so proclucing organisms are resistant to it. patients who have undergone splenectomy have an increased An oxyimino cephalosporin (e.g., cef.epime) (Option risk of developing more severe disease and dying from A) shoulcl not be used el,en if an ESBL producing organism this protozoan infection. Artesunate is the drug of choice, appears to be susceptible through laboratory testing. Treat- with transition to an oral antimalarial medication such as ment failures are comrlon, even with higher doses. artemether-lumefantrine, atovaquone-proguanil, doxycycline, Colistin (Option B) is generally reserved for the treat- or quinine sulfate to complete the course of treatment when ment of multidrug-resistant gram-negative infections, signiflcant improvement has been achieved. Intensive med- including those caused by carbapenem-resistant Entero ical care, including hemodynamic and respiratory support, bacteriaceae. Unless a patient has antibiotic allergies that management of fluid and electrolytes, blood replacement, and preclude the use of'a carbapenem or another agent active possibly hemodialysis, is also immediately required. against ESBL producing E. coli. colistin should be avoided. Atovaquone-proguanil (Option B) and quinine sulfate Fosfbmycin (Option D) is a bactericidal, oral ar-rtibiotic can be used to treat all malarial species regardless of chloro- (in the United States) w'ith gram negative :rnd granr positive quine sensitivity, but they are not recommended for severe activity (including nrethicillin resistant Stophylococcus malaria. aureus and vanconrycin-resistant enterococci). It achieves All Plosmodium species invade hepatocytes. However, high concentrations in the urine and n-ray be usecl fbr treating only P uiuax and P ouale have a latent hepatic stage (hyp- uncomplicated urinary tract ir-rfbctions caused by vancontycin nozoites). Following the treatment of the erythrocytic stage, resistant enterococci and other multidrug-resistant uropatho primaquine or tafenoquine (Option C, D) is given to prevent gens. including ESBl-producing gram negative organisms. clinical relapse by eradicating persistent infection in the Because of'limited systemic absorption. fosfbmlain should not liver. These drugs are not used in the treatment of erythro- be used fbr pyelonephritis or bacteremia. cytic malaria or for severe malaria.

one. and cefepime. The carbapenem class of antibiotics (imi- (>10'/,) accompanied by one or more clinical (e.g., pulmonary penem, meropenem. doripenetri. ertapenem) is the preferred edema, seizures and confusion, bleeding, jaundice, shock) group of agents for treating inf'ections rvitl-r ESBl-producing and laboratory (e.g., severe anemia, kidney injury metabolic organisms. Ertapenem has an advantage over the other acidosis, hypoglycemia, hemoglobinuria) criteria. The spleen carbapenems rt ith once-daily oral dosing, but some ESBL- functions to fllter and clear malaria-infected erythrocytes, so proclucing organisms are resistant to it. patients who have undergone splenectomy have an increased An oxyimino cephalosporin (e.g., cef.epime) (Option risk of developing more severe disease and dying from A) shoulcl not be used el,en if an ESBL producing organism this protozoan infection. Artesunate is the drug of choice, appears to be susceptible through laboratory testing. Treat- with transition to an oral antimalarial medication such as ment failures are comrlon, even with higher doses. artemether-lumefantrine, atovaquone-proguanil, doxycycline, Colistin (Option B) is generally reserved for the treat- or quinine sulfate to complete the course of treatment when ment of multidrug-resistant gram-negative infections, signiflcant improvement has been achieved. Intensive med- including those caused by carbapenem-resistant Entero ical care, including hemodynamic and respiratory support, bacteriaceae. Unless a patient has antibiotic allergies that management of fluid and electrolytes, blood replacement, and preclude the use of'a carbapenem or another agent active possibly hemodialysis, is also immediately required. against ESBL producing E. coli. colistin should be avoided. Atovaquone-proguanil (Option B) and quinine sulfate Fosfbmycin (Option D) is a bactericidal, oral ar-rtibiotic can be used to treat all malarial species regardless of chloro- (in the United States) w'ith gram negative :rnd granr positive quine sensitivity, but they are not recommended for severe activity (including nrethicillin resistant Stophylococcus malaria. aureus and vanconrycin-resistant enterococci). It achieves All Plosmodium species invade hepatocytes. However, high concentrations in the urine and n-ray be usecl fbr treating only P uiuax and P ouale have a latent hepatic stage (hyp- uncomplicated urinary tract ir-rfbctions caused by vancontycin nozoites). Following the treatment of the erythrocytic stage, resistant enterococci and other multidrug-resistant uropatho primaquine or tafenoquine (Option C, D) is given to prevent gens. including ESBl-producing gram negative organisms. clinical relapse by eradicating persistent infection in the Because of'limited systemic absorption. fosfbmlain should not liver. These drugs are not used in the treatment of erythro- be used fbr pyelonephritis or bacteremia. cytic malaria or for severe malaria. 166

Answers and Critiques rEY POI IIT be negative. Finally, the presence of splenomegaly makes o Patients with severe malaria should be treated initially streptococci a much less likely possibility. with intravenous artesunate and then transitioned to r(EY P0l]tTS an oral antimalarial regimen when clinically stable. . Infectious mononucleosis, most commonly caused by Epstein-Barr virus, is usually seen in adolescents who Bibliography have been exposed to oral secretions and typically Centers for Disease Control and Prevention. Treatment of malaria: Guidelines for clinicians (United States). Last updated December 11. presents with fever, nonexudative pharyngitis, lym- 2019. Available at https://www.cdc.gov/malariaidiagnosis treatment/ phadenopathy, and splenomegaly. cliniciansl.html. Accessed April 1, 2020. o Patients with three or more Centor criteria (fever by history tonsillar exudates, tender anterior cervical Item 55 Answer: C lymphadenopathy, and absence of cough) should be vt Educational Objective: Diagnose Epstein-Barr virus tested by using a rapid antigen detection test. o infection. a- - GT Bibliography F II This is a classic presentation for infectious mononucleo L AbuSalah MAH, Gan SH, Al Hat:rmleh MAI, et al. Recent advances in diirg t, sis, most commonly caused by Epstein Barr virus (EBV) nostic approaches for epstein-barr virus. Pathogens. 2020;9. IPN4ID' (Option C). tt is usually seen in adolescents who have Sugl sqsl doi 1 0. 339 0,'pathogens9030226 : =t E fE been exposed to oral secretions. Mononucleosis typically ta L (l, presents with fever, nonexudative pharyngitis, lymphade- Item 56 Answer: A nopathy, splenomegaly, and occasionally a maculopapular tt = rash (5%,-15%) in the absence of antibiotic therapy. Atyp- Ed ucationa I Objective : Prevent travel-related infection - G

rEY POI IIT be negative. Finally, the presence of splenomegaly makes o Patients with severe malaria should be treated initially streptococci a much less likely possibility. with intravenous artesunate and then transitioned to r(EY P0l]tTS an oral antimalarial regimen when clinically stable. . Infectious mononucleosis, most commonly caused by Epstein-Barr virus, is usually seen in adolescents who Bibliography have been exposed to oral secretions and typically Centers for Disease Control and Prevention. Treatment of malaria: Guidelines for clinicians (United States). Last updated December 11. presents with fever, nonexudative pharyngitis, lym- 2019. Available at https://www.cdc.gov/malariaidiagnosis treatment/ phadenopathy, and splenomegaly. cliniciansl.html. Accessed April 1, 2020. o Patients with three or more Centor criteria (fever by history tonsillar exudates, tender anterior cervical Item 55 Answer: C lymphadenopathy, and absence of cough) should be vt Educational Objective: Diagnose Epstein-Barr virus tested by using a rapid antigen detection test. o infection. a- - GT Bibliography F II This is a classic presentation for infectious mononucleo L AbuSalah MAH, Gan SH, Al Hat:rmleh MAI, et al. Recent advances in diirg t, sis, most commonly caused by Epstein Barr virus (EBV) nostic approaches for epstein-barr virus. Pathogens. 2020;9. IPN4ID' (Option C). tt is usually seen in adolescents who have Sugl sqsl doi 1 0. 339 0,'pathogens9030226 : =t E fE been exposed to oral secretions. Mononucleosis typically ta L (l, presents with fever, nonexudative pharyngitis, lymphade- Item 56 Answer: A nopathy, splenomegaly, and occasionally a maculopapular tt = rash (5%,-15%) in the absence of antibiotic therapy. Atyp- Ed ucationa I Objective : Prevent travel-related infection - G in an immunocompromised patient. ical lymphocytosis and aminotransferase level elevations are clues to the diagnosis, which is established by the The most appropriate preventive management for this patient presence of heterophile antibodies (Monospot test) or IgM is administration of the hepatitis A and capsular polysaccha to the EBV viral capsid antigen. The Monospot test result ride Szphoid vaccines (Option A). Depending on the level may be negative in the flrst week of illness. Treatment of immune suppression, travel itinerary and trip duration, is supportive; glucocorticoids may be given to patients immunocompromised travelers are at greater risk of dis with autoimmune hemolytic anemia, central nervous sys ease acquisition and more severe illness. Recommended and tem involvement, or tonsillar enlargement with a com required vaccinations must be individualized for each trav- promised airway. Patients with splenomegaly should be eler's immune status. Live vaccines are contraindicated in warned not to participate in contact sports because of the persons with signiflcant immune compromise, either from risk of splenic rupture. disease or immunosuppressive medication. Regardless of Two other viral causes of infectious mononucleosis syn immune status, all susceptible persons can safely receive the dromes are acute infection with cytomegalovirus or acute inactivated hepatitis A vaccine, which should be administered HIV infection (Option A). The clinical presentations for both as early as possible before travel to countries with intermedi viruses are similar to EBV and can only be differentiated ate to high hepatitis A endemicity. Immunization with either by cytomegalovirus or HIV serologies. This patient has had the multidose live-attenuated oral typhoid or the single-dose no known HIV risk exposure, so HIV would be an unlikely intramuscular capsular polysaccharide typhoid vaccine pro- cause of his mononucleosis syndrome. Because this patient vides similar protection; however, the capsular polysaccha- may be reluctant to share accurate information about his ride vaccine is more appropriate in this immunosuppressed sexual history testing is still advisable. transplant recipient. The onset of respiratory diphtheria (Option B) is gradual The dengue vaccine (not available in the United and most typically presents as sore throat, malaise, cervi States) (Option B) is only indicated for persons aged 9 to cal lymphadenopathy, and low-grade fever. As the disease 16 years who have laboratory-conflrmed previous den- advances, gray and white pharyngeal exudate may be noted gue infection. No data exist regarding the saf'ety of the as well as, in some, formation of a pseudomembrane that live attenuated oral cholera vaccine in immunocolrlpro adheres tightly to the underlying tissues. This patient's pre- mised persons, so it should not be administered following sentation is not typical for respiratory diphtheria, and this transplantation. infection would not be expected in a patient with a com- Persons born before 1957 are presumed to have natural pleted vaccination series. immunity to measles, so vaccination is not recommended Group A Streptococcus pAogenes (Option D) is also an for this patient. Immune globulin administered with the unlikely possibility for this patient's illness. Patients with hepatitis A vaccine is reserved for persons older than three or more Centor criteria (fever by history, tonsillar 40 years, those with chronic liver disease, or persons who exudates, tender anterior cervical lymphadenopathy, and are immunocompromised and planning travel in less than absence of cough) should be tested by using a rapid anti- 2 weeks. None of these indications (Option C) apply to this gen detection test. This patient was tested and found to patient.

in an immunocompromised patient. ical lymphocytosis and aminotransferase level elevations are clues to the diagnosis, which is established by the The most appropriate preventive management for this patient presence of heterophile antibodies (Monospot test) or IgM is administration of the hepatitis A and capsular polysaccha to the EBV viral capsid antigen. The Monospot test result ride Szphoid vaccines (Option A). Depending on the level may be negative in the flrst week of illness. Treatment of immune suppression, travel itinerary and trip duration, is supportive; glucocorticoids may be given to patients immunocompromised travelers are at greater risk of dis with autoimmune hemolytic anemia, central nervous sys ease acquisition and more severe illness. Recommended and tem involvement, or tonsillar enlargement with a com required vaccinations must be individualized for each trav- promised airway. Patients with splenomegaly should be eler's immune status. Live vaccines are contraindicated in warned not to participate in contact sports because of the persons with signiflcant immune compromise, either from risk of splenic rupture. disease or immunosuppressive medication. Regardless of Two other viral causes of infectious mononucleosis syn immune status, all susceptible persons can safely receive the dromes are acute infection with cytomegalovirus or acute inactivated hepatitis A vaccine, which should be administered HIV infection (Option A). The clinical presentations for both as early as possible before travel to countries with intermedi viruses are similar to EBV and can only be differentiated ate to high hepatitis A endemicity. Immunization with either by cytomegalovirus or HIV serologies. This patient has had the multidose live-attenuated oral typhoid or the single-dose no known HIV risk exposure, so HIV would be an unlikely intramuscular capsular polysaccharide typhoid vaccine pro- cause of his mononucleosis syndrome. Because this patient vides similar protection; however, the capsular polysaccha- may be reluctant to share accurate information about his ride vaccine is more appropriate in this immunosuppressed sexual history testing is still advisable. transplant recipient. The onset of respiratory diphtheria (Option B) is gradual The dengue vaccine (not available in the United and most typically presents as sore throat, malaise, cervi States) (Option B) is only indicated for persons aged 9 to cal lymphadenopathy, and low-grade fever. As the disease 16 years who have laboratory-conflrmed previous den- advances, gray and white pharyngeal exudate may be noted gue infection. No data exist regarding the saf'ety of the as well as, in some, formation of a pseudomembrane that live attenuated oral cholera vaccine in immunocolrlpro adheres tightly to the underlying tissues. This patient's pre- mised persons, so it should not be administered following sentation is not typical for respiratory diphtheria, and this transplantation. infection would not be expected in a patient with a com- Persons born before 1957 are presumed to have natural pleted vaccination series. immunity to measles, so vaccination is not recommended Group A Streptococcus pAogenes (Option D) is also an for this patient. Immune globulin administered with the unlikely possibility for this patient's illness. Patients with hepatitis A vaccine is reserved for persons older than three or more Centor criteria (fever by history, tonsillar 40 years, those with chronic liver disease, or persons who exudates, tender anterior cervical lymphadenopathy, and are immunocompromised and planning travel in less than absence of cough) should be tested by using a rapid anti- 2 weeks. None of these indications (Option C) apply to this gen detection test. This patient was tested and found to patient. 167

Answers and Critiques The live-attenuated oral typhoid vaccine is contraindi- infection or as part of combination therapy against the pep cated in this immunosuppressed patient; the yellow fever tic ulcer disease-associated pathogen Helicobacter pylori. vaccine is a live virus vaccine and is contraindicated in Fidaxomicin (Option C), a novelmacrocyclic antibiotic transplant recipients and other immunosuppressed patients that inhibits RNA polymerase, is approved for treatment of (Option D). Following vaccine administration, a viremia Clostridioides difficile infection but has little to no activity often develops persisting for 1 to 3 weeks. Yellow fever vac against enteric gram-negative bacteria like Campylobacter -

The live-attenuated oral typhoid vaccine is contraindi- infection or as part of combination therapy against the pep cated in this immunosuppressed patient; the yellow fever tic ulcer disease-associated pathogen Helicobacter pylori. vaccine is a live virus vaccine and is contraindicated in Fidaxomicin (Option C), a novelmacrocyclic antibiotic transplant recipients and other immunosuppressed patients that inhibits RNA polymerase, is approved for treatment of (Option D). Following vaccine administration, a viremia Clostridioides difficile infection but has little to no activity often develops persisting for 1 to 3 weeks. Yellow fever vac against enteric gram-negative bacteria like Campylobacter - cination is strongly contraindicated in those with compro Although metronidazole (Option D) has activity against mised immune systems because it can result in a particularly some gastrointestinal pathogens, including Entamoeba, aggressive infection in these patients. Giardia, H. pylori, and C. dfficile, it is not reliably effective against Campylobacter and would not be considered for KEY PO I f{TS empiric therapy. o Live vaccines are contraindicated in most persons Campylobacter is inherently resistant to vancomycin with immune compromise. (Option E), so this agent would not be considered for treat- -a UI o Inactivated, recombinant, and capsular polysaccharide ment of infection by this organism. Oral vancomycin is vaccines are safe to administer because they are not approved to treat C. dfficile infection. = .D - Ut live vaccines. o, t(EY POll{T5 -a CL . Diarrhea caused by Campylobacter usually resolves n { Bibliography spontaneously. ,+ l.eung DT, LaRocque RC, Ryan ET. Trarel medicine. Ann Intern Med. -a 2018;168:lTC1 -lTC16. [pUIO, ZSzgtoSS] doi 1O.7326 iAITC201801020 o Patients who have severe Campylobocfer-related 4t E diarrhea (bloody stools, bacteremia, high fever, or .D UT prolonged [>t week] symptoms) or are at risk for Item 57 Answer: B severe disease (immunocompromised persons, pregnant patients, or older adults) should receive Ed u cati o na I O bjective : Treat Campylobacter in a patient who is immunocompromised. azithromycin treatment or prophylaxis.

cination is strongly contraindicated in those with compro Although metronidazole (Option D) has activity against mised immune systems because it can result in a particularly some gastrointestinal pathogens, including Entamoeba, aggressive infection in these patients. Giardia, H. pylori, and C. dfficile, it is not reliably effective against Campylobacter and would not be considered for KEY PO I f{TS empiric therapy. o Live vaccines are contraindicated in most persons Campylobacter is inherently resistant to vancomycin with immune compromise. (Option E), so this agent would not be considered for treat- -a UI o Inactivated, recombinant, and capsular polysaccharide ment of infection by this organism. Oral vancomycin is vaccines are safe to administer because they are not approved to treat C. dfficile infection. = .D - Ut live vaccines. o, t(EY POll{T5 -a CL . Diarrhea caused by Campylobacter usually resolves n { Bibliography spontaneously. ,+ l.eung DT, LaRocque RC, Ryan ET. Trarel medicine. Ann Intern Med. -a 2018;168:lTC1 -lTC16. [pUIO, ZSzgtoSS] doi 1O.7326 iAITC201801020 o Patients who have severe Campylobocfer-related 4t E diarrhea (bloody stools, bacteremia, high fever, or .D UT prolonged [>t week] symptoms) or are at risk for Item 57 Answer: B severe disease (immunocompromised persons, pregnant patients, or older adults) should receive Ed u cati o na I O bjective : Treat Campylobacter in a patient who is immunocompromised. azithromycin treatment or prophylaxis. This patient, who is immunocompromised and has diar Bibliography rhea caused by Campylobacter, a microaerophilic gram Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of negative bacilli, should receive empiric azithromycin therapy America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65:e45 e80. [pl,ltO' zgoszlszl (Option B) . Campylobacter- associated infection is usually doi : 10. 1093 /cid,1cix669 foodborne, often following consumption of inadequately cooked poultry. The incubation period is about 3 days, and symptoms typically include diarrhea (visibly bloody in Item 58 Answer: A approximately 15% of patients), crampy abdominal pain, Ed u cati o n a I O bj ective : Diagnose cytomegalovirus colitis. and fever. Stool culture and molecular testing can be used for diagnosis, although culture is needed to determine the Cytomegalovirus is most likely responsible for this patient's antibiotic susceptibilities of the organism. Diarrhea usu illness (Option A). Approximately 60% to 90% of adults have ally resolves spontaneously without antibiotics. However, latent cytomegalovirus infection, with reactivation of disease patients who have severe disease (bloody stools, bacteremia, common in persons who are immunosuppressed (e.g.. patients high fever, or prolonged [>1 week] symptoms) or are at risk with AIDS, transplant recipients, patients taking glucocorti- for severe disease, including immunocompromised persons, coids). Q.tomegalovirus is a signiflcant pathogen in solid organ pregnant patients, or older adults, should receive antibiotic transplant recipients. The risk of cytomegalovirus infection therapy. When indicated, macrolide therapy with azithro- is highest when a seronegative recipient (one who has never mycin is preferred empirically because of increasing fluor- had a cytomegalovirus infection) receives a solid organ from a oquinolone resistance, particularly in certain geographic seropositive donor. Q,tomegalovirus can cause retinitis (espe locations, including Southeast Asia. Drugs that are usually cially in persons with AIDS), pneumonitis, hepatitis, bone mar active against Campylobacter include aminoglycosides and row suppression, colitis with bloody diarrhea (such as in this carbapenems; trimethoprim-sulfamethoxazole and tetracy patient), esophagitis, and adrenalitis. This patient underwent clines may potentially be effective also. Treatment duration liver transplantation and has bloody diarrhea consistent with with azithromycin is typically 3 days, but a longer course cytomegalovirus reactivation. Diagnosis relies on isolation of may be indicated in immunocompromised persons. Other the virus from bodily fluids, such as S€nlrrr; detection of cy.to gastrointestinal illnesses that can potentially be treated with megalovirus p65 antigen in leukocytes; cytopathic demonstra- azithromycin include travelers' diarrhea or diarrhea caused tion of "owl's eye" intracellular inclusions from tissue biopsy; by Vibrio cholerae, Salmonella, or Shigella. polymerase chain reaction; and serologic assays. Campylobocterexhibits high rates of resistance against Epstein-Barr virus (EBV) (Option B) causes posttrans amoxicillin (Option A), making it a less ideal empiric anti plant lymphoproliferative disorder (PTLD). Patients can biotic choice. Amoxicillin can be used to treat Salmonella have fever, pancytopenia, generalized lymphadenopathy,

This patient, who is immunocompromised and has diar Bibliography rhea caused by Campylobacter, a microaerophilic gram Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of negative bacilli, should receive empiric azithromycin therapy America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65:e45 e80. [pl,ltO' zgoszlszl (Option B) . Campylobacter- associated infection is usually doi : 10. 1093 /cid,1cix669 foodborne, often following consumption of inadequately cooked poultry. The incubation period is about 3 days, and symptoms typically include diarrhea (visibly bloody in Item 58 Answer: A approximately 15% of patients), crampy abdominal pain, Ed u cati o n a I O bj ective : Diagnose cytomegalovirus colitis. and fever. Stool culture and molecular testing can be used for diagnosis, although culture is needed to determine the Cytomegalovirus is most likely responsible for this patient's antibiotic susceptibilities of the organism. Diarrhea usu illness (Option A). Approximately 60% to 90% of adults have ally resolves spontaneously without antibiotics. However, latent cytomegalovirus infection, with reactivation of disease patients who have severe disease (bloody stools, bacteremia, common in persons who are immunosuppressed (e.g.. patients high fever, or prolonged [>1 week] symptoms) or are at risk with AIDS, transplant recipients, patients taking glucocorti- for severe disease, including immunocompromised persons, coids). Q.tomegalovirus is a signiflcant pathogen in solid organ pregnant patients, or older adults, should receive antibiotic transplant recipients. The risk of cytomegalovirus infection therapy. When indicated, macrolide therapy with azithro- is highest when a seronegative recipient (one who has never mycin is preferred empirically because of increasing fluor- had a cytomegalovirus infection) receives a solid organ from a oquinolone resistance, particularly in certain geographic seropositive donor. Q,tomegalovirus can cause retinitis (espe locations, including Southeast Asia. Drugs that are usually cially in persons with AIDS), pneumonitis, hepatitis, bone mar active against Campylobacter include aminoglycosides and row suppression, colitis with bloody diarrhea (such as in this carbapenems; trimethoprim-sulfamethoxazole and tetracy patient), esophagitis, and adrenalitis. This patient underwent clines may potentially be effective also. Treatment duration liver transplantation and has bloody diarrhea consistent with with azithromycin is typically 3 days, but a longer course cytomegalovirus reactivation. Diagnosis relies on isolation of may be indicated in immunocompromised persons. Other the virus from bodily fluids, such as S€nlrrr; detection of cy.to gastrointestinal illnesses that can potentially be treated with megalovirus p65 antigen in leukocytes; cytopathic demonstra- azithromycin include travelers' diarrhea or diarrhea caused tion of "owl's eye" intracellular inclusions from tissue biopsy; by Vibrio cholerae, Salmonella, or Shigella. polymerase chain reaction; and serologic assays. Campylobocterexhibits high rates of resistance against Epstein-Barr virus (EBV) (Option B) causes posttrans amoxicillin (Option A), making it a less ideal empiric anti plant lymphoproliferative disorder (PTLD). Patients can biotic choice. Amoxicillin can be used to treat Salmonella have fever, pancytopenia, generalized lymphadenopathy, 168

Answers and Critiques and hepatosplenomegaly. PTLD risk is higher in patients ernpiric therapy fbr both Pseudontonns and MRSA is rec- with a history of pre-existing EBV infection treated with ommended for sev-ere (e.g.. requiring ICU care) CAP Antibi- lymphocyte-depleting agents and in those receiving otic de escalation can be pursuecl if cultures are negatire at sirolimus and tacrolimus compared with those receiv- 48 hours. ing mycophenolate and cyclosporine. This patient has no Vancomycin is unnecessary in this patient u,ho does generalized lymphadenopathy or hepatosplenomegaly, and not have risk factors for MRSA pneunronia (e.g.. previous bloody diarrhea is not a common presentation of PTLD. MRSA gronth in a respiratory specimen. recent hospitaliza- Herpes simplex virus type 1 (Option C) can reactivate tion w'ith parenteral antibiotics, injection drug use), so the after solid organ transplantation, but the most common combination of cefepime. vancomycin, and levofloracin is manifestation is oral ulcers and, occasionally, tracheobron- not indicated (Option B). chitis or esophagitis. Herpes simplex virus does not cause No antifungal therapy is necessary in this patient bloody diarrhea. despite the Gram stain findings. so the reginren containing Polyoma BK virus (Option D) reactivation occurs in micaf'ungin would be unnecessary (Option C). The presence ra q, approximately Sul, of kidney transplant recipients and can of yeast in a respiratory specimen is rarely clinically signifi- - ET cause kidney allograft dysfunction or loss. It would be cant but rather represents oropharyngeal colonization w,ith F unusual to see BK nephropathy in liver transplant recipients. Candida species. Furthermore, the acute onset of symptoms L rJ It can present with a gradual, asymptomatic increase in the in this patient argues against a fungal cause. -te serum creatinine level with tubulointerstitial nephritis or, Ceftaroline (combined with a second agent such as - tE less commonly, ureteral stenosis. Patients may have po$oma azithromycin) could be a CAP therapy option fbr a patient tt L (, BK virus on polymerase chain reaction of the urine or serum who does not have risk factors fbr Pseudomoncs (Option or may have polyoma BK virus inclusion-bearing epithelial D). However. this antibiotic lacks antipseudomonal activ- ;=ut cells called "decoy cells" on urine microscopy. Po$oma BK ity'. so it would not be an appropriate choice fbr this virus does not cause bloody diarrhea as in this patient. patient.

and hepatosplenomegaly. PTLD risk is higher in patients ernpiric therapy fbr both Pseudontonns and MRSA is rec- with a history of pre-existing EBV infection treated with ommended for sev-ere (e.g.. requiring ICU care) CAP Antibi- lymphocyte-depleting agents and in those receiving otic de escalation can be pursuecl if cultures are negatire at sirolimus and tacrolimus compared with those receiv- 48 hours. ing mycophenolate and cyclosporine. This patient has no Vancomycin is unnecessary in this patient u,ho does generalized lymphadenopathy or hepatosplenomegaly, and not have risk factors for MRSA pneunronia (e.g.. previous bloody diarrhea is not a common presentation of PTLD. MRSA gronth in a respiratory specimen. recent hospitaliza- Herpes simplex virus type 1 (Option C) can reactivate tion w'ith parenteral antibiotics, injection drug use), so the after solid organ transplantation, but the most common combination of cefepime. vancomycin, and levofloracin is manifestation is oral ulcers and, occasionally, tracheobron- not indicated (Option B). chitis or esophagitis. Herpes simplex virus does not cause No antifungal therapy is necessary in this patient bloody diarrhea. despite the Gram stain findings. so the reginren containing Polyoma BK virus (Option D) reactivation occurs in micaf'ungin would be unnecessary (Option C). The presence ra q, approximately Sul, of kidney transplant recipients and can of yeast in a respiratory specimen is rarely clinically signifi- - ET cause kidney allograft dysfunction or loss. It would be cant but rather represents oropharyngeal colonization w,ith F unusual to see BK nephropathy in liver transplant recipients. Candida species. Furthermore, the acute onset of symptoms L rJ It can present with a gradual, asymptomatic increase in the in this patient argues against a fungal cause. -te serum creatinine level with tubulointerstitial nephritis or, Ceftaroline (combined with a second agent such as - tE less commonly, ureteral stenosis. Patients may have po$oma azithromycin) could be a CAP therapy option fbr a patient tt L (, BK virus on polymerase chain reaction of the urine or serum who does not have risk factors fbr Pseudomoncs (Option or may have polyoma BK virus inclusion-bearing epithelial D). However. this antibiotic lacks antipseudomonal activ- ;=ut cells called "decoy cells" on urine microscopy. Po$oma BK ity'. so it would not be an appropriate choice fbr this virus does not cause bloody diarrhea as in this patient. patient. KEY POIT{T KEY POIl{T . Cytomegalovirus is a significant pathogen in solid o Empiric therapy for Pseudomonas community-acquired organ transplant recipients and can cause retinitis, pneumonia is recommended in two situations: growth pneumonitis, hepatitis, bone marrow suppression, from a respiratory tract culture in the previous year, colitis with bloody diarrhea, esophagitis, and or hospitalization and parenteral antibiotics in the adrenalitis. preceding 3 months.

KEY POIT{T KEY POIl{T . Cytomegalovirus is a significant pathogen in solid o Empiric therapy for Pseudomonas community-acquired organ transplant recipients and can cause retinitis, pneumonia is recommended in two situations: growth pneumonitis, hepatitis, bone marrow suppression, from a respiratory tract culture in the previous year, colitis with bloody diarrhea, esophagitis, and or hospitalization and parenteral antibiotics in the adrenalitis. preceding 3 months. Bibliography Bibliography Kumar R, Ison MG. Opporlunistic infections in transplant patients. Infect Dis Restrepo MI, Babu BL, Reyes LF, et al; GLIMP. Burden and risk factors for Clin Norlh Am. 2019;33 :1143 -tt57. [PMID: et06stss] doi:10.1016/j.idc. Pseudomonas aeruginosa community-acquired pneumonia: a multina- 201S.0.s.008 tional point prevalence study of hospitalised patients. Eur Respir J. 2018;52. [PMID, ZgSl00St] doi:10.1183/13993003.0119 0-20t7 Item 59 Answer: A Ed ucati ona I O bjective : Treat severe community- Item 6O Answer: D acquired pneumonia in a patient with risk factors for Educational Objective: Screen for sexually transmitted Pseudomonos infection. infections.

Item 59 Answer: A Ed ucati ona I O bjective : Treat severe community- Item 6O Answer: D acquired pneumonia in a patient with risk factors for Educational Objective: Screen for sexually transmitted Pseudomonos infection. infections. The most appropriate initial treatment for this patient This sexually active young woman should be screened for is cefepime and levofloxacin (Option A). She has severe chlamydia, gonorrhea, HIV infection, and syphilis (Option community-acquired pneumonia (CAP) that requires an anti- D). She is younger than 25 years and at high risk for sexually biotic regimen with corerage fbr Pseudomonas aeruginosa. transmitted infections (STIs) because she has multiple part- Guidelines recognize two scenarios when empiric therapy ners and inconsistently uses condoms. Other risk factors for Pseudomonos is indicated: (1) growth from a respiratory include a new sex partner in the previous 60 days; having tract culture in the previous year. or (2) hospitalization and sex with a partner recently treated for an STI; sex for money parenteral antibiotics in the preceding 3 months (w'hich is or drugs; sex with sex workers; sfld sex with anonymous also a risk factor for methicillin-resistant SfcrphylococcLts partners. The U.S. Preventive Services Task Force (USPSTF) aureus [MRSA] CAP). Pseudomonos accounts for less than recommends screening for syphilis in all pregnant women 5'X, of all CAP infections; hou'ever. previous isolation of the and in nonpregnant adults and adolescents at high risk for organism from sputum is associated with a 16 fold increased STIs. Half of STIs diagnosed are in the 15- to 24-year age risk of subsequent infection. Other risk factors fbr Pseudo- range, underscoring the importance of screening in this age monos CAP include previous tracheostomy. bronchiectasis. group. Her age and high-risk STI status necessitate screen- and severe COPD. In patients who have been hospitalized in ing for chlamydia and gonorrhea; HIV testing would also the preceding 3 months and received parenteral antibiotics. be recommended (Option B), as would syphilis screening.

The most appropriate initial treatment for this patient This sexually active young woman should be screened for is cefepime and levofloxacin (Option A). She has severe chlamydia, gonorrhea, HIV infection, and syphilis (Option community-acquired pneumonia (CAP) that requires an anti- D). She is younger than 25 years and at high risk for sexually biotic regimen with corerage fbr Pseudomonas aeruginosa. transmitted infections (STIs) because she has multiple part- Guidelines recognize two scenarios when empiric therapy ners and inconsistently uses condoms. Other risk factors for Pseudomonos is indicated: (1) growth from a respiratory include a new sex partner in the previous 60 days; having tract culture in the previous year. or (2) hospitalization and sex with a partner recently treated for an STI; sex for money parenteral antibiotics in the preceding 3 months (w'hich is or drugs; sex with sex workers; sfld sex with anonymous also a risk factor for methicillin-resistant SfcrphylococcLts partners. The U.S. Preventive Services Task Force (USPSTF) aureus [MRSA] CAP). Pseudomonos accounts for less than recommends screening for syphilis in all pregnant women 5'X, of all CAP infections; hou'ever. previous isolation of the and in nonpregnant adults and adolescents at high risk for organism from sputum is associated with a 16 fold increased STIs. Half of STIs diagnosed are in the 15- to 24-year age risk of subsequent infection. Other risk factors fbr Pseudo- range, underscoring the importance of screening in this age monos CAP include previous tracheostomy. bronchiectasis. group. Her age and high-risk STI status necessitate screen- and severe COPD. In patients who have been hospitalized in ing for chlamydia and gonorrhea; HIV testing would also the preceding 3 months and received parenteral antibiotics. be recommended (Option B), as would syphilis screening. 169

Answers and Critiques Additionally, counseling regarding the importance of con- r.t,illrestore the normal colonic microbiota. Fecal microbiota dom use to decrease STI risk is critical. transplantation is not recommended for the acute treatment Retesting for chlamydia alone (Option A) would be of CDI, regardless of severity. recommended 3 months after treatment of her previous Intravenous vancomycin (Option B) is not recom- infection because of the elevated risk of reinfection. If this mended for treatment of CDI because it is not excreted into was not done, testing at her next appointment would be rec- the large intestine. ommended. Because of the length of time since her infection The 2Ol7 Infectious Diseases Society of America and was treated and her ongoing risk factors, testing for chla- Society for Healthcare Epidemiology of America clinical mydia alone would be inappropriate at this time. practice gr-rideline fbr CDI recommends oral vancomycin Although she is clearly at risk for herpes simplex virus (Option C) or oral fidaxomicin to treat an initial episode of (HSV), the USPSTF recommends against screening with nonse\ere or severe CDI. Nonsevere CDI is deflned as a leu- type-speciflc antibodies for HSV-1 and HSV-2 (Option C) in kocyte count of less than 15,000/pL (15 x 10erl) and a serum asymptomatic adolescents and adults, including pregnant creatinine level less than 1.5 mg/dl (133 pmol/L): severe J UI women. disease is associated with a higher leukocyte count or serLlm E (D The incidence of the three reportable bacterial STIs, syph- creatinine level. If both agents are unavailable or intolerable, - UI ilis, gonorrhea, and chlamydia, has increased at an alarming then oral metronidazole (Option D) can be used but only in o, rate in the United States. The Centers for Disease Control and nonsevere disease. J CL Prevention reported a 79% increase in chlamydia infections, r,} rEY POIl{T - t -o 63o1, increase in gonorrhea infections, and 7l'/nincrease in pri- . Fulminant Clostridioides dfficile infection, which is mary and secondary syphilis between 2014 and 2018. Of grave st -a associated with hypotension, shock, ileus, or megacolon, E (D concern is the increase in congenital syphilis, with 1306 cases la reported in 2018, an increase of 185% compared with 2014. should be treated with a combination of oral vancomycin and intravenous metronidazole. r(tY Por ilrs o Persons at high risk for sexually transmitted infections Bibliography include those who are younger than 25 !€srS; incon- McDonald LC. Gerding DN, Johnson S, et al. Clinical practice guidelines for sistent condom use; having a new sex partner or mul- Clostridium dfficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare tiple sexual partners; having a partner with a recently Epidemiologr of America (SHEA). Clin Infect Dis. 2018;66:987 994. treated sexually transmitted infection; having sex IPMID: ZgSOZZe|l doi:10.1093/cid I ciyl49

Additionally, counseling regarding the importance of con- r.t,illrestore the normal colonic microbiota. Fecal microbiota dom use to decrease STI risk is critical. transplantation is not recommended for the acute treatment Retesting for chlamydia alone (Option A) would be of CDI, regardless of severity. recommended 3 months after treatment of her previous Intravenous vancomycin (Option B) is not recom- infection because of the elevated risk of reinfection. If this mended for treatment of CDI because it is not excreted into was not done, testing at her next appointment would be rec- the large intestine. ommended. Because of the length of time since her infection The 2Ol7 Infectious Diseases Society of America and was treated and her ongoing risk factors, testing for chla- Society for Healthcare Epidemiology of America clinical mydia alone would be inappropriate at this time. practice gr-rideline fbr CDI recommends oral vancomycin Although she is clearly at risk for herpes simplex virus (Option C) or oral fidaxomicin to treat an initial episode of (HSV), the USPSTF recommends against screening with nonse\ere or severe CDI. Nonsevere CDI is deflned as a leu- type-speciflc antibodies for HSV-1 and HSV-2 (Option C) in kocyte count of less than 15,000/pL (15 x 10erl) and a serum asymptomatic adolescents and adults, including pregnant creatinine level less than 1.5 mg/dl (133 pmol/L): severe J UI women. disease is associated with a higher leukocyte count or serLlm E (D The incidence of the three reportable bacterial STIs, syph- creatinine level. If both agents are unavailable or intolerable, - UI ilis, gonorrhea, and chlamydia, has increased at an alarming then oral metronidazole (Option D) can be used but only in o, rate in the United States. The Centers for Disease Control and nonsevere disease. J CL Prevention reported a 79% increase in chlamydia infections, r,} rEY POIl{T - t -o 63o1, increase in gonorrhea infections, and 7l'/nincrease in pri- . Fulminant Clostridioides dfficile infection, which is mary and secondary syphilis between 2014 and 2018. Of grave st -a associated with hypotension, shock, ileus, or megacolon, E (D concern is the increase in congenital syphilis, with 1306 cases la reported in 2018, an increase of 185% compared with 2014. should be treated with a combination of oral vancomycin and intravenous metronidazole. r(tY Por ilrs o Persons at high risk for sexually transmitted infections Bibliography include those who are younger than 25 !€srS; incon- McDonald LC. Gerding DN, Johnson S, et al. Clinical practice guidelines for sistent condom use; having a new sex partner or mul- Clostridium dfficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare tiple sexual partners; having a partner with a recently Epidemiologr of America (SHEA). Clin Infect Dis. 2018;66:987 994. treated sexually transmitted infection; having sex IPMID: ZgSOZZe|l doi:10.1093/cid I ciyl49 with a sex worker; sex with anonymous partners; or Item 62 trading sex for drugs or money. o Patients at high risk for sexually transmitted infections Answer: C Educational Objective: Treat herpes simplex virus tr should be screened for chlamydia, gonorrhea, syphilis, encephalitis. and HIV infection. Acyclovir should be continued and antibiotics discontinued (Option C); additionally, the polymerase chain reaction (PCR) Bibliography for herpes simplex virus (HSV) type 1 should be repeated Ler,y SB, Gunta J, Edemekong P Screening for sexually transmitted diseases. Prim Care. 2079:46:157'173. [PMID: 30704656] doi:10.1016/j.PoP. in 1 lteek. This patient has the ffpical cerebrospinal fluid 2018.10.013 (CSF) findings of HSV encephalitis, including a lymphocytic pleocltosis. an elevated protein level, and a normal glucose level. This patient also has the classic imaging findings of Item 61 tr Answer: E Educational ObjeAive: Treat an initial episode of unilateral temporal lobe enhancement. HSV PCR of the CSF conflrms the diagnosis; however. false-negative results have been reported. If HSV is suspected, a repeat PCR should be fulminant Clostridioides dilficile infection. obtained within l week while continuing acyclovir therapy. This patient has fulminant Clostridioides dfficile infection Antibiotic treatment (Option A, B) should be discon- (CDI) and should be treated with oral vancomycin and intra- tinued because the CSF profile is not consistent with acute venous metronidazole (Option E). Fulminant infection is bacterial meningitis, and CSF Gram stain and culture and defined as CDI with associated hypotension, shock, ileus, or multiplex PCR for bacteria are negative. Bacterial meningitis megacolon. Oral vancomycin (by mouth or nasogastric tube) usually presents acutely (within 1 2 days of symptom initi- plus intravenous metronidazole are recommended for fulmi- ation) r.tith headache. stiffneck. and altered mental status; nant CDI. If an ileus is present, rectal instillation of vanco- laboratory flndings include a CSF leukocyte count greater mycin should be considered. Patients with fulminant disease than 1000/pL (1000 x 106rL) with a neutrophilic predom- warrant surgical evaluation as r.tell. inance in 90'l, of patients, a very high CSF protein level Fecal microbiota transplantation (Option A) has been (too-soo mg/dl ltooo-sooo mg/L1), and severe hypoglycor- recommended as a treatment approach for patients rn ith rhachia <40 mg/dl (Z.Z mmol/L). This patient's findings are multiple relapses of CDI. The rationale is that donor feces not compatible rnith bacterial meningitis.

with a sex worker; sex with anonymous partners; or Item 62 trading sex for drugs or money. o Patients at high risk for sexually transmitted infections Answer: C Educational Objective: Treat herpes simplex virus tr should be screened for chlamydia, gonorrhea, syphilis, encephalitis. and HIV infection. Acyclovir should be continued and antibiotics discontinued (Option C); additionally, the polymerase chain reaction (PCR) Bibliography for herpes simplex virus (HSV) type 1 should be repeated Ler,y SB, Gunta J, Edemekong P Screening for sexually transmitted diseases. Prim Care. 2079:46:157'173. [PMID: 30704656] doi:10.1016/j.PoP. in 1 lteek. This patient has the ffpical cerebrospinal fluid 2018.10.013 (CSF) findings of HSV encephalitis, including a lymphocytic pleocltosis. an elevated protein level, and a normal glucose level. This patient also has the classic imaging findings of Item 61 tr Answer: E Educational ObjeAive: Treat an initial episode of unilateral temporal lobe enhancement. HSV PCR of the CSF conflrms the diagnosis; however. false-negative results have been reported. If HSV is suspected, a repeat PCR should be fulminant Clostridioides dilficile infection. obtained within l week while continuing acyclovir therapy. This patient has fulminant Clostridioides dfficile infection Antibiotic treatment (Option A, B) should be discon- (CDI) and should be treated with oral vancomycin and intra- tinued because the CSF profile is not consistent with acute venous metronidazole (Option E). Fulminant infection is bacterial meningitis, and CSF Gram stain and culture and defined as CDI with associated hypotension, shock, ileus, or multiplex PCR for bacteria are negative. Bacterial meningitis megacolon. Oral vancomycin (by mouth or nasogastric tube) usually presents acutely (within 1 2 days of symptom initi- plus intravenous metronidazole are recommended for fulmi- ation) r.tith headache. stiffneck. and altered mental status; nant CDI. If an ileus is present, rectal instillation of vanco- laboratory flndings include a CSF leukocyte count greater mycin should be considered. Patients with fulminant disease than 1000/pL (1000 x 106rL) with a neutrophilic predom- warrant surgical evaluation as r.tell. inance in 90'l, of patients, a very high CSF protein level Fecal microbiota transplantation (Option A) has been (too-soo mg/dl ltooo-sooo mg/L1), and severe hypoglycor- recommended as a treatment approach for patients rn ith rhachia <40 mg/dl (Z.Z mmol/L). This patient's findings are multiple relapses of CDI. The rationale is that donor feces not compatible rnith bacterial meningitis. 170

Answers and Criti ques H C0NT . o. o :',?T,Ti, #,ff ;i'?J?H: lf,:l : T : ;ff:il : * fl ' cl,rssic presentation fbr autoimmune encephalitis if the ini- : (Option C) is the ntost recent F'DA approved drug to prevent cytomegalovirus inf'ection in bone marro\A/ transplant recip ients. Foscarnet, cidofbvir, and leterntovir are r-rot indicated tial evaluation is negative fbr a viral cause. Repeat HSV pCR in this patient u,ith relatively milcl disease who will ntost has not yet been perfbrmed for this patient, and the clinical likely respond to oral valganciclovir theraplr presentation and imaging findings are not consistent with autoinrmune encephalitis. lhe benefit of glucocorticoids XEY POI lIT in viral encephalitis has not been documented, but some o Intravenous ganciclovir is indicated as initial therapy experts recomfilend their use if significant brain edema or for severe cytomegalovirus infection in immunosup- mass eflbct is present. pressed patients; milder disease can be treated with I( EY POI t{T oral valganciclovir.

cl,rssic presentation fbr autoimmune encephalitis if the ini- : (Option C) is the ntost recent F'DA approved drug to prevent cytomegalovirus inf'ection in bone marro\A/ transplant recip ients. Foscarnet, cidofbvir, and leterntovir are r-rot indicated tial evaluation is negative fbr a viral cause. Repeat HSV pCR in this patient u,ith relatively milcl disease who will ntost has not yet been perfbrmed for this patient, and the clinical likely respond to oral valganciclovir theraplr presentation and imaging findings are not consistent with autoinrmune encephalitis. lhe benefit of glucocorticoids XEY POI lIT in viral encephalitis has not been documented, but some o Intravenous ganciclovir is indicated as initial therapy experts recomfilend their use if significant brain edema or for severe cytomegalovirus infection in immunosup- mass eflbct is present. pressed patients; milder disease can be treated with I( EY POI t{T oral valganciclovir. o Patients with suspected herpes simplex virus enceph_ Bibliography ta alitis with a negative initial polymerase chain reaction Clausen ES, Zaffiri L. Inf'ection prophylaxis and management of viral infec, o J result should undergo repeat lumbar puncture in 3 to tion. Ann Transl Med. 2020;8(6):415. [ptr,llO, SZssseSS] doi:7O.2to37t ET ar atm.2019.11.85 F 7 days; antiviral therapy should be continued until a- L repeat results are available. TJ .E, E Item 64 Answer: C (E Bibliography a L Venkatesan A, Michael BD, Probasco JC, et al. Acute encephalitis in immu Educational Obiective: Evaluate a patient with o nocompetent adults. Lancet. 2019;393:702 ztO. [pMID: nZAZSqq] communit5r-acquired pneumonia for influenza in the vl doi:10.1016/S0140-6736(18)SZSZ0 t outpatient setting. = - The most helpful diagnostic test is the rapid influenza Item 63 tr Answer: D Educational Objective: Treat cytomegalovirus colitis. nucleic acid amplification test (NAAT) (Option C). Molec- ular assays are preferred for the diagnosis of influenza over the older rapid influenza antigen test because of superior The most appropriate empiric therapy is valganciclovir sensitivity (Option B). A history of influenza vaccination (Option D). Cytornegalovirus is an important pathogen in does not preclude an influenza diagnosis. Reasons for infec- transplant recipients. and the risk of cy.tomegalovirus ir-rf'ec- tion despite immunization include an inability to mount tion depends on the serologic status of tl-re patient. The highest an immunologic response or discordance between vaccine risk occurs when a seronegative recipient obtains a graft from strains and those circulating in the community. A positive a c'_vtomegalovims seropositive donor because the recipient influenza test result does not exclude the possibility of a Iacks cy.tomegalovirus-specific immunity that can protect bacterial coinfection, so when influenza is suspected or thern fiom prirnary cytomegalovirus inf'ection from the donor conflrmed, antibiotic therapy should be given in addition to organ. Cy'tomegalovirus inlbction can develop in up to 70'X, of antiviral treatment. Infectious Diseases Society of America patients who are cytomegalovirus seropositive if prophylaxis and American Thoracic Society guidelines for community is not given. Cytomegalovirus infbcticln can cause retinitis, acquired pneumonia (CAP) recommend starting oseltamivir pneumonitis, encephalitis, hepatitis, bone marro\ / suppres in all adults with CAP and laboratory-confirmed influenza sion. colitis r,vith bloodl, diarrhea. esophagitis, and adrenal- independent of symptom duration. Therefore, a positive itis. Cytomegalovirus is an immunomodulatory virus (active rapid influenza NAAT would influence management, and infbction also results in nonspecific changes in immune sys- testing should be performed routinely on patients with tem function), and cytomegalovirus reactivation is associated CAP during seasons when influenza activity is present in rtith organ rejection, secondary infbction, and an increased the community. risl< for graft loss and death. Diagnosis relies on detection of Procalcitonin level has been studied as a biomarker cytomegalovirus by polymerase chain reaction (PCR) (serum. to distinguish viral from bacterial CAP but is not suffi cerebrospinal fluid, bronchioalveolar lavage, or vitreous fluid ciently sensitive to differentiate these causes (Option A). sample), detection of cytomegalovirus p65 antigen in leuko- Because antibiotics are recommended for all patients with cytes, or by cytopathic demonstration of "owl's eye" intracel- CAP regardless of procalcitonin results, testing would not lular inclusions or positive imnrunohistochemical stains fron-r change clinical management and should not be performed. tissue biopsy. Severe infection is treated with intravenous Sputum and blood cultures should be considered in gar-rciclovir; milder disease can be treated r,vith oral valganci hospitalized patients or in patients with risk factors for clovir and avoids the potential hazard of central line infection. methicillin resistant Staphylococcus aureus or Pseudomo- Oral valganciclovir is also used as prophylaxis or pre-emptive nos oeruginoso (Option D). In these cases, results would therapy (treat if the PCR serum testing result converts to pos- inform narrowing or de-escalation of antibiotic therapy. itive) in transplant recipients. Resistant pathogens are less likely in patients with mild Cidoftrvir and foscarnet (Option A, B) can be used in presentations of CAP, and respiratory tract cultures in this instances of ganciclovir resistance or intolerance. Letermovir population have not been shown to improve outcomes.

o Patients with suspected herpes simplex virus enceph_ Bibliography ta alitis with a negative initial polymerase chain reaction Clausen ES, Zaffiri L. Inf'ection prophylaxis and management of viral infec, o J result should undergo repeat lumbar puncture in 3 to tion. Ann Transl Med. 2020;8(6):415. [ptr,llO, SZssseSS] doi:7O.2to37t ET ar atm.2019.11.85 F 7 days; antiviral therapy should be continued until a- L repeat results are available. TJ .E, E Item 64 Answer: C (E Bibliography a L Venkatesan A, Michael BD, Probasco JC, et al. Acute encephalitis in immu Educational Obiective: Evaluate a patient with o nocompetent adults. Lancet. 2019;393:702 ztO. [pMID: nZAZSqq] communit5r-acquired pneumonia for influenza in the vl doi:10.1016/S0140-6736(18)SZSZ0 t outpatient setting. = - The most helpful diagnostic test is the rapid influenza Item 63 tr Answer: D Educational Objective: Treat cytomegalovirus colitis. nucleic acid amplification test (NAAT) (Option C). Molec- ular assays are preferred for the diagnosis of influenza over the older rapid influenza antigen test because of superior The most appropriate empiric therapy is valganciclovir sensitivity (Option B). A history of influenza vaccination (Option D). Cytornegalovirus is an important pathogen in does not preclude an influenza diagnosis. Reasons for infec- transplant recipients. and the risk of cy.tomegalovirus ir-rf'ec- tion despite immunization include an inability to mount tion depends on the serologic status of tl-re patient. The highest an immunologic response or discordance between vaccine risk occurs when a seronegative recipient obtains a graft from strains and those circulating in the community. A positive a c'_vtomegalovims seropositive donor because the recipient influenza test result does not exclude the possibility of a Iacks cy.tomegalovirus-specific immunity that can protect bacterial coinfection, so when influenza is suspected or thern fiom prirnary cytomegalovirus inf'ection from the donor conflrmed, antibiotic therapy should be given in addition to organ. Cy'tomegalovirus inlbction can develop in up to 70'X, of antiviral treatment. Infectious Diseases Society of America patients who are cytomegalovirus seropositive if prophylaxis and American Thoracic Society guidelines for community is not given. Cytomegalovirus infbcticln can cause retinitis, acquired pneumonia (CAP) recommend starting oseltamivir pneumonitis, encephalitis, hepatitis, bone marro\ / suppres in all adults with CAP and laboratory-confirmed influenza sion. colitis r,vith bloodl, diarrhea. esophagitis, and adrenal- independent of symptom duration. Therefore, a positive itis. Cytomegalovirus is an immunomodulatory virus (active rapid influenza NAAT would influence management, and infbction also results in nonspecific changes in immune sys- testing should be performed routinely on patients with tem function), and cytomegalovirus reactivation is associated CAP during seasons when influenza activity is present in rtith organ rejection, secondary infbction, and an increased the community. risl< for graft loss and death. Diagnosis relies on detection of Procalcitonin level has been studied as a biomarker cytomegalovirus by polymerase chain reaction (PCR) (serum. to distinguish viral from bacterial CAP but is not suffi cerebrospinal fluid, bronchioalveolar lavage, or vitreous fluid ciently sensitive to differentiate these causes (Option A). sample), detection of cytomegalovirus p65 antigen in leuko- Because antibiotics are recommended for all patients with cytes, or by cytopathic demonstration of "owl's eye" intracel- CAP regardless of procalcitonin results, testing would not lular inclusions or positive imnrunohistochemical stains fron-r change clinical management and should not be performed. tissue biopsy. Severe infection is treated with intravenous Sputum and blood cultures should be considered in gar-rciclovir; milder disease can be treated r,vith oral valganci hospitalized patients or in patients with risk factors for clovir and avoids the potential hazard of central line infection. methicillin resistant Staphylococcus aureus or Pseudomo- Oral valganciclovir is also used as prophylaxis or pre-emptive nos oeruginoso (Option D). In these cases, results would therapy (treat if the PCR serum testing result converts to pos- inform narrowing or de-escalation of antibiotic therapy. itive) in transplant recipients. Resistant pathogens are less likely in patients with mild Cidoftrvir and foscarnet (Option A, B) can be used in presentations of CAP, and respiratory tract cultures in this instances of ganciclovir resistance or intolerance. Letermovir population have not been shown to improve outcomes. 171

Answers and Critiques Malaria (Option D) is one of the most common diagno- XEY PO I IIIS ses in returning travelers with fever. However, it would be . The rapid influenza nucleic acid amplification test is rare to develop infection while taking tafenoquine chemo- recommended for diagnosis over previous rapid anttgen prophylaxis. tests because of superior sensitivity. I(EY POI ilTS . Influenza testing should be performed routinely on patients with community-acquired pneumonia dur- . Brucellosis is characterized by intermittent fever with periods of remission lasting several weeks or may per- ing seasons when influenza activity is present in the sist for months. community because a positive result would influence treatment. . Brucellosis is commonly associated with hepatosple- nomegaly, arthralgia, and depression. Bibliography D Metlay JB Waterer GW. Long AC. et al. Diagnosis and treatment of adults Bibliography J UI wiih community-acquired pneumonia. An official clinical practice Glowacka P, Zakowska D, Naylor K, et al. Brucella - virulence factors, patho- guideline of the American Thoracic Society and Infectious Diseases genesis and treatment. Poi J Microbiol. 2018;67:151-161. [PMID: goots+Ss] (D Society of America. Am J Respir Crit Care Med. 2019;200:e45 e67. [PMID: = rl 315733501 doi :10.1164/rccm. 201908- I 581ST doi:10.21307/Pjm 2018-029 UI q, J CL a.t -J+ I' Item 65 Answer: A Educational Objective: Diagnose brucellosis. Item 66 Answer: B Educational Obiective: Manage cryptococcal meningitis tr a? in a patient with AIDS. The most likely diagnosis is brucellosis (Option A), commonly .D UI referred to as "undulant fever" because of its up-and-down Lumbar puncture (rn ith documentation of opening pressure fever pattern. Although the incidence of infection with this measurement) to alleviate intracranial pressure (lCP) is the gram-negative, intracellular, coccobacillus is highest in Med- most appropriate next step in management for this patient iterranean countries, it is also commonly encountered in the (Option B). The patient's presentation and the positive serum Middle East and South and Central America. Infection with cryptococcal antigen test indicate he has cryptococcal menin- tkre Brucello species that cause illness in humans (8. abortus, gitis. Cryptococcosis-related increased ICP may result it-t sttd- B. melitensis, B. suis, B. conis) generally follows ingestion of den blindness, deafness, or coma. Apgressive reduction of ICP undercooked meat, raw milk, or contaminated milk products with lumbar puncture reduces early morbidity and mortality. or through direct contact with secretions and excretions of Early repeat lumbar puncture should be performed in patients infected animals. Symptom onset may be sudden, with chills with persistent symptoms during antifungal induction ther- and fever, severe headache, joint and back pain, malaise, and apy and for recurrent symptoms after initial improvement. overall lethargr. Intermittent fever with periods of remission Although he has another fungal opportunistic infbction lasting several weeks is common and may persist for months. (oral c:rndidiasis), which is often treated with fluconazole, Depression is commonly reported. Hepatosplenomegaly and the prescribed amphotericin B will manage it (Option A). lymphadenopathy are frequently detected on physical exam- Fluconazole is fungistatic against cryptococcal inf'ections ination. Cl.topenias and abnormal liver chemistry results are and has been shown to be inferior to initial treatment witl-t nonspeciflc laboratory flndings. Diagnosis is best made by iso combination amphotericin B and flucytosine, which is fun- lation of the bacteria from blood cultures; however, the rate of gicidal. detection is variable. The organism may also be isolated from In patients with recently diagr-rosed HIV infection and bone marrow culture, especially in chronic disease. Serologic concomitant cryptococcal rneningitis, early initiation of testing is often relied on when cultures are negative. antiretroviral tl-rerapy (ART) (within 2 weeks) contpared Coxiella burnetii is the causative agent of Q fever with delayed initiation has been shown to increase mortality (Option B). Inhalation of aerosolized soil contaminated with at 30 days and at 6 months (Option C, D). The difference in excrement or birth by-products from infected goats, sheep, mortality is even higher if the cerebrospinal fluid leukocyte and cattle is the major mode of transmission to humans. A count is less than 5 cells/pL (s x tot'lL). Risks related to early mild, self-limited febrile illness, sometimes with pneumonia ART initiation are higl-rer in resource-lirnited settings. In the and hepatitis, is the most frequent clinical presentation, and United States and at centers with access to optimal antifirn- endocarditis is a major chronic manifestation. This patient's gal therapy (amphotericin B) and the ability to monitor clin- chronic febrile illness is not typical for Q fever. ical status and intracranial pressure (inclucling assessntents Most patients infected with Histoplasma capsulatum for repeat lumbar puncture for drainage), ART cnn be started (Option C) experience fever, a nonproductive cough, and between 2 and 10 weeks of HIV diagnosis while the patient chest discomfort as the most common manifestations. In receives antifungal therapy. However, cautious monitoring those who develop chronic infection, lung involvement is {br cornplicatior-rs, ir-rcludir-rg ICP and immune reconstitu- predominant. Cavitary lesions and mediastinal lymphade- tion inflammatory syndrome, would be paramount in these nopathy are typical flndings, which are not present in this cases. If that is not f'easible, ART initiation should be delayed patient. until 10 weeks of cryptococcal meningitis treatment has

Malaria (Option D) is one of the most common diagno- XEY PO I IIIS ses in returning travelers with fever. However, it would be . The rapid influenza nucleic acid amplification test is rare to develop infection while taking tafenoquine chemo- recommended for diagnosis over previous rapid anttgen prophylaxis. tests because of superior sensitivity. I(EY POI ilTS . Influenza testing should be performed routinely on patients with community-acquired pneumonia dur- . Brucellosis is characterized by intermittent fever with periods of remission lasting several weeks or may per- ing seasons when influenza activity is present in the sist for months. community because a positive result would influence treatment. . Brucellosis is commonly associated with hepatosple- nomegaly, arthralgia, and depression. Bibliography D Metlay JB Waterer GW. Long AC. et al. Diagnosis and treatment of adults Bibliography J UI wiih community-acquired pneumonia. An official clinical practice Glowacka P, Zakowska D, Naylor K, et al. Brucella - virulence factors, patho- guideline of the American Thoracic Society and Infectious Diseases genesis and treatment. Poi J Microbiol. 2018;67:151-161. [PMID: goots+Ss] (D Society of America. Am J Respir Crit Care Med. 2019;200:e45 e67. [PMID: = rl 315733501 doi :10.1164/rccm. 201908- I 581ST doi:10.21307/Pjm 2018-029 UI q, J CL a.t -J+ I' Item 65 Answer: A Educational Objective: Diagnose brucellosis. Item 66 Answer: B Educational Obiective: Manage cryptococcal meningitis tr a? in a patient with AIDS. The most likely diagnosis is brucellosis (Option A), commonly .D UI referred to as "undulant fever" because of its up-and-down Lumbar puncture (rn ith documentation of opening pressure fever pattern. Although the incidence of infection with this measurement) to alleviate intracranial pressure (lCP) is the gram-negative, intracellular, coccobacillus is highest in Med- most appropriate next step in management for this patient iterranean countries, it is also commonly encountered in the (Option B). The patient's presentation and the positive serum Middle East and South and Central America. Infection with cryptococcal antigen test indicate he has cryptococcal menin- tkre Brucello species that cause illness in humans (8. abortus, gitis. Cryptococcosis-related increased ICP may result it-t sttd- B. melitensis, B. suis, B. conis) generally follows ingestion of den blindness, deafness, or coma. Apgressive reduction of ICP undercooked meat, raw milk, or contaminated milk products with lumbar puncture reduces early morbidity and mortality. or through direct contact with secretions and excretions of Early repeat lumbar puncture should be performed in patients infected animals. Symptom onset may be sudden, with chills with persistent symptoms during antifungal induction ther- and fever, severe headache, joint and back pain, malaise, and apy and for recurrent symptoms after initial improvement. overall lethargr. Intermittent fever with periods of remission Although he has another fungal opportunistic infbction lasting several weeks is common and may persist for months. (oral c:rndidiasis), which is often treated with fluconazole, Depression is commonly reported. Hepatosplenomegaly and the prescribed amphotericin B will manage it (Option A). lymphadenopathy are frequently detected on physical exam- Fluconazole is fungistatic against cryptococcal inf'ections ination. Cl.topenias and abnormal liver chemistry results are and has been shown to be inferior to initial treatment witl-t nonspeciflc laboratory flndings. Diagnosis is best made by iso combination amphotericin B and flucytosine, which is fun- lation of the bacteria from blood cultures; however, the rate of gicidal. detection is variable. The organism may also be isolated from In patients with recently diagr-rosed HIV infection and bone marrow culture, especially in chronic disease. Serologic concomitant cryptococcal rneningitis, early initiation of testing is often relied on when cultures are negative. antiretroviral tl-rerapy (ART) (within 2 weeks) contpared Coxiella burnetii is the causative agent of Q fever with delayed initiation has been shown to increase mortality (Option B). Inhalation of aerosolized soil contaminated with at 30 days and at 6 months (Option C, D). The difference in excrement or birth by-products from infected goats, sheep, mortality is even higher if the cerebrospinal fluid leukocyte and cattle is the major mode of transmission to humans. A count is less than 5 cells/pL (s x tot'lL). Risks related to early mild, self-limited febrile illness, sometimes with pneumonia ART initiation are higl-rer in resource-lirnited settings. In the and hepatitis, is the most frequent clinical presentation, and United States and at centers with access to optimal antifirn- endocarditis is a major chronic manifestation. This patient's gal therapy (amphotericin B) and the ability to monitor clin- chronic febrile illness is not typical for Q fever. ical status and intracranial pressure (inclucling assessntents Most patients infected with Histoplasma capsulatum for repeat lumbar puncture for drainage), ART cnn be started (Option C) experience fever, a nonproductive cough, and between 2 and 10 weeks of HIV diagnosis while the patient chest discomfort as the most common manifestations. In receives antifungal therapy. However, cautious monitoring those who develop chronic infection, lung involvement is {br cornplicatior-rs, ir-rcludir-rg ICP and immune reconstitu- predominant. Cavitary lesions and mediastinal lymphade- tion inflammatory syndrome, would be paramount in these nopathy are typical flndings, which are not present in this cases. If that is not f'easible, ART initiation should be delayed patient. until 10 weeks of cryptococcal meningitis treatment has 172

Answers and Critiques tr CONI been completed. Additionally. patients who are prescribed abacavir must first undergo testing to show they are HLA_ Liver biopsy (Option C) is considered when liver chem- istry tests are abnormal and an abdominal CT scan suggests 8"57:01 negative to reduce the risk of l-rypersensitivity. an abnormality; testing is therefore not indicated in this KEY POIT{TS patient. o Cryptococcal meningitis-related increased intracranial t(EY P0lt{Ts pressure may result in sudden blindness, deafness, or o In patients with classic fever of unknown origin (fever coma. >38.3 'C [100.9 'F] for >3 weeks that remains undiag- . Aggressive reduction of intracranial pressure with nosed after careful extensive evaluation and two visits lumbar puncture reduces cryptococcal meningitis- in the ambulatory setting), no further testing or treat- related early morbidity and mortality. ment is indicated. o The prognosis for fever of unknown origin is good for Bibliography adults who remain undiagnosed after extensive evalu UI Panel on Opportunistic Infections in HIV Infected Adults and Adolescents. o ation. CT J Guidelines for the prevention and treatment of opportunistic infections a-

tr CONI been completed. Additionally. patients who are prescribed abacavir must first undergo testing to show they are HLA_ Liver biopsy (Option C) is considered when liver chem- istry tests are abnormal and an abdominal CT scan suggests 8"57:01 negative to reduce the risk of l-rypersensitivity. an abnormality; testing is therefore not indicated in this KEY POIT{TS patient. o Cryptococcal meningitis-related increased intracranial t(EY P0lt{Ts pressure may result in sudden blindness, deafness, or o In patients with classic fever of unknown origin (fever coma. >38.3 'C [100.9 'F] for >3 weeks that remains undiag- . Aggressive reduction of intracranial pressure with nosed after careful extensive evaluation and two visits lumbar puncture reduces cryptococcal meningitis- in the ambulatory setting), no further testing or treat- related early morbidity and mortality. ment is indicated. o The prognosis for fever of unknown origin is good for Bibliography adults who remain undiagnosed after extensive evalu UI Panel on Opportunistic Infections in HIV Infected Adults and Adolescents. o ation. CT J Guidelines for the prevention and treatment of opportunistic infections a- in HIV infected adults and adolescents: recommendations from the f a- L Centers for Disease Control and Prevention, the National Institutes of Bibliography IJ Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated lune 26, 2019. Available at https://aidsinfo. Wright WF, Auwaerter PG. Fever and fever of unknown origin: review =, L nih.gov/guidelines/htmll 4/adult-and adolescent-opportunistic-infec recent advances, and lingering dogma. Open Forum Infect Dis. 2O2O;7: TE ofaa1S2. Iptr,ltn, 324 620$] doi: 10. 1093 /ofi d/of aa1 32 ta tion/333/cryptococcosis. Accessed February 24, 2020. L q, vt Item 68 Answer: C = E Item 67 Answer: D Ed ucationa I Objective : Diagnose Legionello pneumonia. Educational Objective: Evaluate fever of unknown orign. Despite the negative Legionella urine antigen test, the most Clinical observation is the most appropriate management at likely diagnosis in this patient is Legionello pneumonia this time (Option D). The patient meets the criteria for clas- (Option C). Legionello causes 2% to 15'ln of community- sic fever of unknown origin (pUO)' fever greater than 38.3 'C acquired pneumonia (CAP) illnesses but is likely under- (tOO.g'F) for more than 3 weeks that remains undiagnosed recognized. Several clinical and epidemiologic clues suggest a after two visits in the ambulatory setting. A careful, detailed Legionella pneumonia diagnosis in this patient. Most impor- history is the flrst step in evaluating a patient with FUO. The tant is the clustering of infections among cotravelers exposed history should be repeated at each visit because subtle clues to a common water source. Legionella has been associated may be revealed onlywith repeated questioning. A complete with inhalation of infectious aerosols from water sources, medical, occupational, and social history should be elicited including air conditioning cooling units, spas, pools, foun- followed by a careful comprehensive examination to guide tains, and showers. Features that are variably present but may further testing. When the initial evaluation is unrevealing, suggest Legionella include gastrointestinal symptoms (includ- CT of the abdomen and pelvis (with and without contrast) ing diarrhea), altered mentation, pulse-temperature dissoci- should be obtained. When imaging results are normal, con- ation, increased liver en4zmes, and hyponatremia. The 2019 tinued clinical observation is the appropriate next step. The Infectious Diseases Society of America and American Thoracic prognosis is good for adults who remain undiagnosed after Society guidelines recommend conditional testing for Legio- extensive evaluation (nearly half of patients remain undiag- nello urinary antigen when suggestive epidemiologic features nosed), and fever often spontaneously resolves in weeks to are present, such as an outbreak, or in cases of severe pneumo- months. nia. This test only detects L. pneumophilo serogroup 1, which Bone marrow biopsy (Option A) is generally considered accounts for between 7Oo/n and 90% of laboratory diagnosed when the complete blood count is abnormal. It is helpful in CAP in the United States; other species or serogroups would be establishing the diagnosis of disseminated granulomatosis missed through urinary antigen testing but may be identifled (e.g., tuberculosis, histoplasmosis) or malignancy (e.g., leu- by culture of respiratory specimens on selective media. kemia, lymphoma). Wrestlers are at risk for herpes gladiatorum, a cutane- Empiric trials of systemic glucocorticoids (Option B), ous infection with herpes simplex virus Upe 1, but not her- antibiotics, or NSAIDs are rarely indicated for FUO. Such pes simplex pneumonia, which typically occurs in severely empiric trials do not establish a diagnosis and may delay immunocompromised patients (Option A). determining the correct diagnosis. Empiric glucocorticoids Histoplasmosis is an important endemic mycosis in are only considered if suspicion is strong for a rheumato- Indiana and the Ohio and Mississippi River Valleys but logic cause such as temporal arteritis but should not replace causes a more indolent pulmonary infection and would not obtaining the appropriate biopsies for diagnosis. Biopsy of improve with standard treatment for CAP (Option B). the temporal artery may be indicated in older adult patients Pseudomonos and Mycobacterium auium complex who have an elevated erythrocyte sedimentation rate with- (MAC) are associated with respiratory infection and gran- out localizing symptoms. ulomatous lung disease ("hot tub lung"), respectively,

in HIV infected adults and adolescents: recommendations from the f a- L Centers for Disease Control and Prevention, the National Institutes of Bibliography IJ Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated lune 26, 2019. Available at https://aidsinfo. Wright WF, Auwaerter PG. Fever and fever of unknown origin: review =, L nih.gov/guidelines/htmll 4/adult-and adolescent-opportunistic-infec recent advances, and lingering dogma. Open Forum Infect Dis. 2O2O;7: TE ofaa1S2. Iptr,ltn, 324 620$] doi: 10. 1093 /ofi d/of aa1 32 ta tion/333/cryptococcosis. Accessed February 24, 2020. L q, vt Item 68 Answer: C = E Item 67 Answer: D Ed ucationa I Objective : Diagnose Legionello pneumonia. Educational Objective: Evaluate fever of unknown orign. Despite the negative Legionella urine antigen test, the most Clinical observation is the most appropriate management at likely diagnosis in this patient is Legionello pneumonia this time (Option D). The patient meets the criteria for clas- (Option C). Legionello causes 2% to 15'ln of community- sic fever of unknown origin (pUO)' fever greater than 38.3 'C acquired pneumonia (CAP) illnesses but is likely under- (tOO.g'F) for more than 3 weeks that remains undiagnosed recognized. Several clinical and epidemiologic clues suggest a after two visits in the ambulatory setting. A careful, detailed Legionella pneumonia diagnosis in this patient. Most impor- history is the flrst step in evaluating a patient with FUO. The tant is the clustering of infections among cotravelers exposed history should be repeated at each visit because subtle clues to a common water source. Legionella has been associated may be revealed onlywith repeated questioning. A complete with inhalation of infectious aerosols from water sources, medical, occupational, and social history should be elicited including air conditioning cooling units, spas, pools, foun- followed by a careful comprehensive examination to guide tains, and showers. Features that are variably present but may further testing. When the initial evaluation is unrevealing, suggest Legionella include gastrointestinal symptoms (includ- CT of the abdomen and pelvis (with and without contrast) ing diarrhea), altered mentation, pulse-temperature dissoci- should be obtained. When imaging results are normal, con- ation, increased liver en4zmes, and hyponatremia. The 2019 tinued clinical observation is the appropriate next step. The Infectious Diseases Society of America and American Thoracic prognosis is good for adults who remain undiagnosed after Society guidelines recommend conditional testing for Legio- extensive evaluation (nearly half of patients remain undiag- nello urinary antigen when suggestive epidemiologic features nosed), and fever often spontaneously resolves in weeks to are present, such as an outbreak, or in cases of severe pneumo- months. nia. This test only detects L. pneumophilo serogroup 1, which Bone marrow biopsy (Option A) is generally considered accounts for between 7Oo/n and 90% of laboratory diagnosed when the complete blood count is abnormal. It is helpful in CAP in the United States; other species or serogroups would be establishing the diagnosis of disseminated granulomatosis missed through urinary antigen testing but may be identifled (e.g., tuberculosis, histoplasmosis) or malignancy (e.g., leu- by culture of respiratory specimens on selective media. kemia, lymphoma). Wrestlers are at risk for herpes gladiatorum, a cutane- Empiric trials of systemic glucocorticoids (Option B), ous infection with herpes simplex virus Upe 1, but not her- antibiotics, or NSAIDs are rarely indicated for FUO. Such pes simplex pneumonia, which typically occurs in severely empiric trials do not establish a diagnosis and may delay immunocompromised patients (Option A). determining the correct diagnosis. Empiric glucocorticoids Histoplasmosis is an important endemic mycosis in are only considered if suspicion is strong for a rheumato- Indiana and the Ohio and Mississippi River Valleys but logic cause such as temporal arteritis but should not replace causes a more indolent pulmonary infection and would not obtaining the appropriate biopsies for diagnosis. Biopsy of improve with standard treatment for CAP (Option B). the temporal artery may be indicated in older adult patients Pseudomonos and Mycobacterium auium complex who have an elevated erythrocyte sedimentation rate with- (MAC) are associated with respiratory infection and gran- out localizing symptoms. ulomatous lung disease ("hot tub lung"), respectively, 173

Answers and Critiques following hot tub exposure in an enclosed area (Option D, infection in persons with HIV. Moreover, many of the E). Neither of these pathogens is likely, given the clinical manifestations of MAC and tuberculosis are similar' MAC is course. Pseudomonos would not improve without effec- generally diagnosed by bone marrow biopsy or blood cul- tive antibiotic therapy, and hot tub-associated pneumonia ture for mycobacterial organisms. However, MAC is rarely is very rare. MAC-related disease, thought to be a hyper- seen in patients with HIV with CD4 cell counts greater sensitivity reaction rather than true infection, usually than 50/ptl. occurs following prolonged hot tub exposure and is more t(EY POI llls indolent in presentation. . Risk factors for Mycobacterium tuberculosis infection I(EY POI flIS include HIV infection, substance abuse, and residing o Legionello pneumonia should be suspected in groups in congregate settings. of patients who have recently been exposed to a com- o Active pulmonary tuberculosis should be strongly mon water source. suspected in persons with chronic symptoms of fever, - Vt o Legionello urinary antigen detects L. pneumophila night sweats, weight loss, and productive cough. E serogroup 1; other species or serogroups would be .D -l UI missed through urinary antigen testing. Bibliography q, - a Mendez-samperio P. Diagnosis of tuberculosis in HIV co-infected individu- als: current status, challenges and opportunities for the future. Scand l rl IT Bibliography Immunol. 2OI7 ;86 :7 6 - 82. IPMID : 2851 38651 doi :10. 11i1 /sj i.12567 * -a Chahin A, Opal SM. Severe pneumonia caused by Legionella pneumophila: differential diagnosis and therapeutic considerations. Infect Dis Clin Its North Am. 2017r31 :111 121. IPMID: ZStSStZt] doi:10.i016/j.idc.2016.10.009 Item 7O (D UI Answer: C Educational Objective: Diagnose Heartland virus tr Item 69 Answer: D infection. Educationa I Objective: Diagnose active tuberculosis the patient most likely has Heartland virus, a tick borne infection in a patient with HIV. Phlebot,irtLs (Option C). The Lone Star tick is the vector fbr The most likely organism causing this patient's illness is I{ear1land vims. r.tith human infbctions reported in the Mid Mycobacterium tuberculosis (Option D). He has several westenr and southenr United States. Ehrlichia cholpensis is risk factors for active pulmonary tuberculosis, including transmitted by the same tickr therefbre. the regional distri HIV infection, alcohol use disorder, and history of incar bution of these infections is similar and they are clinically ceration. His complex of symptoms, including ongoing indistinguishable, with common nonspecific symptoms, fever, night sweats, weight loss, and productive cough, also including f'evet headache, rnyalgia, arthralgia, and malaise indicate likely tuberculosis. Although a tuberculin skin test (Option B). Both typically present with leukopeni:t (and, or interferon-y release assay would be useful and should nlore specifically, lymphopeniii), thrombocytopenia, and be performed for all suspected tuberculosis infections, it elevated arninotransf'erase levels. I.leartland virus does not may not be positive in this patient with a CD4 cell count responcl to doxycvcline, and the treatment for this inf'ection of 200/pL. is supportive care, whereas rapid defervescence with doxy In immunocompetent patients, symptoms of pulmo- cycline is an almost universal f'eature fbr ehrlichiosis, ana' nary histoplasmosis (Option A) are typically mild, with plasmosis, ancl spotted f'ever grollp rickettsioses. including headache, fever, and cough, which usually resolve after a Rocky Mount;rin spotted f'ever (RMSF). Lack of improvenrent few weeks. Although data are limited, patients with HIV r,r,ithin 48 honrs of dorlzcycline initiation suggests an alter infection and CD4 cell counts of 200/pL or greater may pre native diagr-rosis. [r-r patients r.t,ith a presentation consistent sent similarly to immunocompetent persons. In this patient, r,r,ith ehrlichiosis who do not improve with doxycyclir-re ther with a more protracted and symptomatic course, negative apy. testing for Heartlancl virus by the Centers fbr Disease yeast following bronchoalveolar lavage, and positive acid Control ancl Prevention can be requested through the state fast bacilli stain, pulmonary tuberculosis is a more likely l"realth departr-nent. diagnosis. Brucella is a zoonotic inf'ection. but vaccination has Mycobacterium obscessus (Option B) is not gener- virtr.rally elinrinated cattle as a reservoir fbr tl-ris inf'ection ally seen in patients with HIV. It usually occurs in patients in the United States (Option A). Internationally ingestion with cystic flbrosis, persons with COPD, recipients of solid of unpasteurized dairv products from sheep or goats or organ or stem cell transplants, and occasionally health care- exposure to ralt, rnilk remain risk factors for brucellosis. associated infections, such as postoperative wound infec- Adclitionally, brucella infection responds to doxycycline tion. It is considered one of the most pathogenic and therapv: resistant mycobacteria and is relatively resistant to most Although the absence of a rash r,r,ould not erclude RN4SF antituberculous antimicrobials. beclruse cutaneous nranifestations often lag up to 1 week Mycobacterium auium complex (MAC) (Option C) is after f'ever onset. doxycycline therapy would have resolved one of the most common causes of generalized and chronic this patient's fbver if he had RMSF (Option D).

following hot tub exposure in an enclosed area (Option D, infection in persons with HIV. Moreover, many of the E). Neither of these pathogens is likely, given the clinical manifestations of MAC and tuberculosis are similar' MAC is course. Pseudomonos would not improve without effec- generally diagnosed by bone marrow biopsy or blood cul- tive antibiotic therapy, and hot tub-associated pneumonia ture for mycobacterial organisms. However, MAC is rarely is very rare. MAC-related disease, thought to be a hyper- seen in patients with HIV with CD4 cell counts greater sensitivity reaction rather than true infection, usually than 50/ptl. occurs following prolonged hot tub exposure and is more t(EY POI llls indolent in presentation. . Risk factors for Mycobacterium tuberculosis infection I(EY POI flIS include HIV infection, substance abuse, and residing o Legionello pneumonia should be suspected in groups in congregate settings. of patients who have recently been exposed to a com- o Active pulmonary tuberculosis should be strongly mon water source. suspected in persons with chronic symptoms of fever, - Vt o Legionello urinary antigen detects L. pneumophila night sweats, weight loss, and productive cough. E serogroup 1; other species or serogroups would be .D -l UI missed through urinary antigen testing. Bibliography q, - a Mendez-samperio P. Diagnosis of tuberculosis in HIV co-infected individu- als: current status, challenges and opportunities for the future. Scand l rl IT Bibliography Immunol. 2OI7 ;86 :7 6 - 82. IPMID : 2851 38651 doi :10. 11i1 /sj i.12567 * -a Chahin A, Opal SM. Severe pneumonia caused by Legionella pneumophila: differential diagnosis and therapeutic considerations. Infect Dis Clin Its North Am. 2017r31 :111 121. IPMID: ZStSStZt] doi:10.i016/j.idc.2016.10.009 Item 7O (D UI Answer: C Educational Objective: Diagnose Heartland virus tr Item 69 Answer: D infection. Educationa I Objective: Diagnose active tuberculosis the patient most likely has Heartland virus, a tick borne infection in a patient with HIV. Phlebot,irtLs (Option C). The Lone Star tick is the vector fbr The most likely organism causing this patient's illness is I{ear1land vims. r.tith human infbctions reported in the Mid Mycobacterium tuberculosis (Option D). He has several westenr and southenr United States. Ehrlichia cholpensis is risk factors for active pulmonary tuberculosis, including transmitted by the same tickr therefbre. the regional distri HIV infection, alcohol use disorder, and history of incar bution of these infections is similar and they are clinically ceration. His complex of symptoms, including ongoing indistinguishable, with common nonspecific symptoms, fever, night sweats, weight loss, and productive cough, also including f'evet headache, rnyalgia, arthralgia, and malaise indicate likely tuberculosis. Although a tuberculin skin test (Option B). Both typically present with leukopeni:t (and, or interferon-y release assay would be useful and should nlore specifically, lymphopeniii), thrombocytopenia, and be performed for all suspected tuberculosis infections, it elevated arninotransf'erase levels. I.leartland virus does not may not be positive in this patient with a CD4 cell count responcl to doxycvcline, and the treatment for this inf'ection of 200/pL. is supportive care, whereas rapid defervescence with doxy In immunocompetent patients, symptoms of pulmo- cycline is an almost universal f'eature fbr ehrlichiosis, ana' nary histoplasmosis (Option A) are typically mild, with plasmosis, ancl spotted f'ever grollp rickettsioses. including headache, fever, and cough, which usually resolve after a Rocky Mount;rin spotted f'ever (RMSF). Lack of improvenrent few weeks. Although data are limited, patients with HIV r,r,ithin 48 honrs of dorlzcycline initiation suggests an alter infection and CD4 cell counts of 200/pL or greater may pre native diagr-rosis. [r-r patients r.t,ith a presentation consistent sent similarly to immunocompetent persons. In this patient, r,r,ith ehrlichiosis who do not improve with doxycyclir-re ther with a more protracted and symptomatic course, negative apy. testing for Heartlancl virus by the Centers fbr Disease yeast following bronchoalveolar lavage, and positive acid Control ancl Prevention can be requested through the state fast bacilli stain, pulmonary tuberculosis is a more likely l"realth departr-nent. diagnosis. Brucella is a zoonotic inf'ection. but vaccination has Mycobacterium obscessus (Option B) is not gener- virtr.rally elinrinated cattle as a reservoir fbr tl-ris inf'ection ally seen in patients with HIV. It usually occurs in patients in the United States (Option A). Internationally ingestion with cystic flbrosis, persons with COPD, recipients of solid of unpasteurized dairv products from sheep or goats or organ or stem cell transplants, and occasionally health care- exposure to ralt, rnilk remain risk factors for brucellosis. associated infections, such as postoperative wound infec- Adclitionally, brucella infection responds to doxycycline tion. It is considered one of the most pathogenic and therapv: resistant mycobacteria and is relatively resistant to most Although the absence of a rash r,r,ould not erclude RN4SF antituberculous antimicrobials. beclruse cutaneous nranifestations often lag up to 1 week Mycobacterium auium complex (MAC) (Option C) is after f'ever onset. doxycycline therapy would have resolved one of the most common causes of generalized and chronic this patient's fbver if he had RMSF (Option D). 174

Answers and Criti ques I(EY POITTS t(EY POtl{TS o Heartland virus presents after a tick bite with non o Oral acyclovir, famciclovir, or valacyclovir speeds specific symptoms of fever, headache, myalgia, recovery and decreases the severity and duration of arthralgia, and malaise. neuropathic pain if begun within 72 hours of'varicella_ o A lack of response to doxycycline therapy distinguishes zoster virus rash onset. Heartland virus infection from other similar tick_borne o Immunosuppressed patients with severe or disseminated diseases. varicella-zoster virus infection should be admitted to the hospital for treatment with intravenous acyclovir. Bibliography Brault AC, Savage HM, Duggal NK, et al. Heartlancl virus epidemiologr, vec- Bibliography tor association, and disease potential. Viruses. 2018110 . [PMID: 3O22343s] t.e P, Rothberg M. Herpes zoster inf'ection. BMl. 2019r364:kS09S. IPMII) doi: 10.3390/v10090498 SO0SOszzl doi:10. I 136/bmj.k509s vt (l, J

I(EY POITTS t(EY POtl{TS o Heartland virus presents after a tick bite with non o Oral acyclovir, famciclovir, or valacyclovir speeds specific symptoms of fever, headache, myalgia, recovery and decreases the severity and duration of arthralgia, and malaise. neuropathic pain if begun within 72 hours of'varicella_ o A lack of response to doxycycline therapy distinguishes zoster virus rash onset. Heartland virus infection from other similar tick_borne o Immunosuppressed patients with severe or disseminated diseases. varicella-zoster virus infection should be admitted to the hospital for treatment with intravenous acyclovir. Bibliography Brault AC, Savage HM, Duggal NK, et al. Heartlancl virus epidemiologr, vec- Bibliography tor association, and disease potential. Viruses. 2018110 . [PMID: 3O22343s] t.e P, Rothberg M. Herpes zoster inf'ection. BMl. 2019r364:kS09S. IPMII) doi: 10.3390/v10090498 SO0SOszzl doi:10. I 136/bmj.k509s vt (l, J Item 71 Item 72 Answer: A CT Answer: A y a-

Item 71 Item 72 Answer: A CT Answer: A y a- t- Ed ucationa I Objective: Treat disseminated cutaneous Ed ucati o n a I O bjective : Treat communit5r- acquired L' L

t- Ed ucationa I Objective: Treat disseminated cutaneous Ed ucati o n a I O bjective : Treat communit5r- acquired L' L pneumonia in an otherwise healthy outpatient. E? herpes zoster infection. Amoxicillin is the most appropriate therapy fbr this patient - ,g This patient should be given intravenous acyclovir (Option ,a (Option A). Her score on the Pneumonia Severity Index L q, A). Varicella-zoster virus (VZV) is a common opportunis- screening scale is zero; therefore, outpatient therapy fbr ut tic inf'ection in solid organ transplant recipients or older = - community acquired pneumonia (CAP) is appropriate. In adults. VZV reactivation (shingles) presents with pain or healthy persons, treatment options are amoxicillin or dox paresthesias in a speciflc dermatome; the characteristic ycycline (Option D). Amoxicillin is preferred in this patient rash develops several days later. In order of frequency, because of her chronic therapy with another tetracycline, the thoracic, trigeminal, lumbar, and cervical cutaneous minocycline, which is a recognized risk factor for devel dermatomes are most often involved. VZV can present opment of doxycycline resistance. An alternative treatment without the typical vesicular rash (zoster sine herpete), option would be monotherapy with a macrolide if local the absence of which should not deter physicians from pneumococcal resistance is less than 257,. ordering polymerase chain reaction testing for VZV in Ceftriaxone and azithromycin or levofloxacin mono the appropriate clinical settings (e.g., central nervous sys- therapy are recommended regimens for hospitalized patients tem infections). Immunosuppressed patients, including with nonsevere pneumonia (Option B, E). Because this pregnant women, can present with multiple dermatomes patient has no risk factors for adverse outcomes, she does affected (disseminated cutaneous disease) or with dis- not require hospitalization and can be safely treated with an seminated visceral disease, which is associated with a oral regimen as an outpatient. high mortality rate. Patients with disseminated cutaneous Cefuroxime and doxycycline or levofloxacin mono- disease may have disseminated visceral disease. Dissemi therapy are appropriate choices for outpatient therapy in nated cutaneous zoster may also appear as a generalized patients with medical comorbidities but are overly broad eruption. Most patients with YZV can be managed in the for a healthy patient with minimal risk factors for resis- outpatient setting with oral medications. However, immu- tant organisms (Option C). Specific conditions for which nocompromised patients with disseminated or otherwise combination oral therapy or a respiratory fluoroquinolone severe herpes zoster should be admitted to the hospital for are indicated include underlying cardiac, respiratory liver, intravenous acyclovir. or kidney disease; diabetes mellitus; malignancy; alcohol Oral acyclovir, famciclovir, or valacyclovir (Option B, C) use disord€r; or asplenia. Specific respiratory fluoroquino- speeds recovery and decreases the severity and duration of lones recommended in the 2019 American Thoracic Society/ neuropathic pain if begun within 72 hours ofYZY rash onset. Infectious Diseases Society of America CAP management However, this immunocompromised patient with cutaneous guideline include levofloxacin, moxifloxacin, and gemiflox- dissemination should be admitted to the hospital for intra- acin; ciprofloxacin is not active against Streptococcus pneu- venous acyclovir. moniae, precluding use of this agent for CAP monotherapy. Recombinant VZV vaccination (Option D) might be considered for this patient after recovery. However, the Advi- rEY POIT{T sory Committee on Immunization Practices has not offered a . In otherwise healthy persons with communi[z-acquired recommendation regarding the use of the recombinant vac- pneumonia, amoxicillin or doxycycline are appropriate cine in immunocompromised patients, and the timing of the treatment options. vaccine administration after an episode of VZY reactivation is unclear. Finally, the VZV vaccine should not be adminis- Bibliography tered to patients who are currently receiving antiviral drugs Metlay JB Waterer GW, Long AC, et al. Diagnosis and treatment of'adults for the treatment of YZY infection. with community acquired pneumonia. An official clinical practice

pneumonia in an otherwise healthy outpatient. E? herpes zoster infection. Amoxicillin is the most appropriate therapy fbr this patient - ,g This patient should be given intravenous acyclovir (Option ,a (Option A). Her score on the Pneumonia Severity Index L q, A). Varicella-zoster virus (VZV) is a common opportunis- screening scale is zero; therefore, outpatient therapy fbr ut tic inf'ection in solid organ transplant recipients or older = - community acquired pneumonia (CAP) is appropriate. In adults. VZV reactivation (shingles) presents with pain or healthy persons, treatment options are amoxicillin or dox paresthesias in a speciflc dermatome; the characteristic ycycline (Option D). Amoxicillin is preferred in this patient rash develops several days later. In order of frequency, because of her chronic therapy with another tetracycline, the thoracic, trigeminal, lumbar, and cervical cutaneous minocycline, which is a recognized risk factor for devel dermatomes are most often involved. VZV can present opment of doxycycline resistance. An alternative treatment without the typical vesicular rash (zoster sine herpete), option would be monotherapy with a macrolide if local the absence of which should not deter physicians from pneumococcal resistance is less than 257,. ordering polymerase chain reaction testing for VZV in Ceftriaxone and azithromycin or levofloxacin mono the appropriate clinical settings (e.g., central nervous sys- therapy are recommended regimens for hospitalized patients tem infections). Immunosuppressed patients, including with nonsevere pneumonia (Option B, E). Because this pregnant women, can present with multiple dermatomes patient has no risk factors for adverse outcomes, she does affected (disseminated cutaneous disease) or with dis- not require hospitalization and can be safely treated with an seminated visceral disease, which is associated with a oral regimen as an outpatient. high mortality rate. Patients with disseminated cutaneous Cefuroxime and doxycycline or levofloxacin mono- disease may have disseminated visceral disease. Dissemi therapy are appropriate choices for outpatient therapy in nated cutaneous zoster may also appear as a generalized patients with medical comorbidities but are overly broad eruption. Most patients with YZV can be managed in the for a healthy patient with minimal risk factors for resis- outpatient setting with oral medications. However, immu- tant organisms (Option C). Specific conditions for which nocompromised patients with disseminated or otherwise combination oral therapy or a respiratory fluoroquinolone severe herpes zoster should be admitted to the hospital for are indicated include underlying cardiac, respiratory liver, intravenous acyclovir. or kidney disease; diabetes mellitus; malignancy; alcohol Oral acyclovir, famciclovir, or valacyclovir (Option B, C) use disord€r; or asplenia. Specific respiratory fluoroquino- speeds recovery and decreases the severity and duration of lones recommended in the 2019 American Thoracic Society/ neuropathic pain if begun within 72 hours ofYZY rash onset. Infectious Diseases Society of America CAP management However, this immunocompromised patient with cutaneous guideline include levofloxacin, moxifloxacin, and gemiflox- dissemination should be admitted to the hospital for intra- acin; ciprofloxacin is not active against Streptococcus pneu- venous acyclovir. moniae, precluding use of this agent for CAP monotherapy. Recombinant VZV vaccination (Option D) might be considered for this patient after recovery. However, the Advi- rEY POIT{T sory Committee on Immunization Practices has not offered a . In otherwise healthy persons with communi[z-acquired recommendation regarding the use of the recombinant vac- pneumonia, amoxicillin or doxycycline are appropriate cine in immunocompromised patients, and the timing of the treatment options. vaccine administration after an episode of VZY reactivation is unclear. Finally, the VZV vaccine should not be adminis- Bibliography tered to patients who are currently receiving antiviral drugs Metlay JB Waterer GW, Long AC, et al. Diagnosis and treatment of'adults for the treatment of YZY infection. with community acquired pneumonia. An official clinical practice 175

Answers and Critiques guideline of the American Thoracic Society and Infectious Diseases Bibliography Society of America. Am J Respir Crit Care Med. 2019;200:e45-e67' [PMID: Gorelik E, Masarwa R, Perlman A, et aI. Fluoroquinolones and cardiovascu 315733501 doi:10.1164/rccm.2019O8-1581ST lar risk: A systematic review meta analysis and network meta analysis' Drug Saf. 2019 ;42:529 538. [PMID: 30368737] doi:10'1007is 40264-018- 0751-2 Item 73 Answer: B Ed ucationa I O biective : Prevent fluoroquinolone adverse effects. Item 74 Answer: D This patient should undergo electrocardiography before cip- Educational Obiective: Screen for tuberculosis in an rofloxacin is initiated (Option B). Fluoroquinolones have been individual with advanced HIV and recovering CD4 cell associated with QT-interval prolongation. Patients particu- count. larly at risk are those with hypokalemia, hypomagnesemia, The interferon y release assay (IGRA) should be repeated and concomitant use of other drugs that cause QT-interval (Option D). This patient has had an excellent response to J prolongation (e.g., macrolides, azoles, amiodarone). Elec- his antiretroviral therapy (ART), with a dramatic reduction ut trocardiography and corrected QT measurement should be E in his HIV RNA and improvement in his CD4 cell count. .D rl performed before starting a fluoroquinolone in patients at The original tuberculosis screening was performed at the UI q, increased risk and periodically thereafter for the duration of same time as his initial HIV diagnosis, which resulted in J treatment. In the absence of additional risk factors, routine a negative IGRA. His previous incarceration places him at EL a'l electrocardiography screening is not necessary. Additional risk for tuberculosis; if he would have acquired tuberculosis rl r-t adverse effects of fluoroquinolones include increased risk of previously, he is also at high risk for progression considering ll-a tendinitis and tendon rupture (most commonly the Achilles his HIV infection. Guidelines recommend that tuberculosis E .D tendon) ; hypog$cemia or hyperglycemia; peripheral neurop- screening be repeated in persons with HIV when the CD4 cell la athy; and neurologic side effects such as delirium, agitation, count rises to 2OOl1tL, especially if previous testing was nega nervousness, and memory impairment. Fluoroquinolones tive and the patient has signiflcant risk factors. also carry a two-fold increased risk of rupture and dissection Mycobacterium auium complex (MAC) infections can of the sorta; they should be avoided in persons who have an be seen in persons with advanced HIV. However, with a aortic aneurysm or are at risk for an aortic aneurysm (e.g., pretreatment CD4 cell count of more than 50/prl and a older adults and those with peripheral atherosclerotic vas- remarkable increase following effective ART, the risk for cular diseases, uncontrolled hypertension, certain genetic MAC related infection is low. Performing acid-fast bacilli conditions) unless no other treatment options are available. blood cultures for evaluation of disseminated MAC infection Mild elevations of aminotransferase levels are an has little to no utility in this patient (Option A). observed effect of fluoroquinolones, but severe liver disease Starting active tuberculosis treatment without conflr- and liver failure are rare. Obtaining pretreatment amino- matory testing for tuberculosis infection is not appropriate transferase levels (Option A) is unnecessary. Statins are an and puts patients at risk for complications from a regimen example of a drug class for which pretreatment amino- with several adverse effects (Option B). transferase measurements are recommended. Similarly, initiating latent tuberculosis treatment The gastrointestinal eflects of fluoroquinolones (anorexia, without a flrm diagnosis would be inappropriate (Option nausea, vomiting, mild abdominal discomfort) do not include C). Although treatment regimens are effective, several pancreatitis, so monitoring the serum lipase level (Option C) (especially rifamycin based regimens) have signiflcant is unnecessar!; regardless, the serum lipase level would not interactions with tenofovir alafenamide and integrase be measured unless the patient had symptoms compatible inhibitors like bictegravir or dolutegravir. If a diagnosis with acute pancreatitis. of latent tuberculosis were established, then treatment Diminished visual acuity is not an adverse effect of fluor- would be provided with isoniazid for 6 to 9 months with oquinolone therapy, and visual acuity screening (Option D) continuation of current ART or a weekly isoniazid and is not necessary before therapy initiation. Changes in visual rifapentine-based regimen for 12 weeks with modiflcation acuity or red-green color blindness is a known adverse effect of his current single-tablet ART regimen. The decision to of treatment with ethambutol and requires visual acuity start latent tuberculosis management should not be made testing before starting the drug. without repeating the IGRA flrst. XEY POITTS Repeat screening for tuberculosis is indicated in this o Fluoroeuinolones are associated with QT-interval pro- patient with HIV and recovering CD4 cell count with the decision to initiate therapy informed by results; therefore, no Iongation, and baseline electrocardiography should be additional testing is not appropriate (Option E). performed and repeated during therapy if other risk factors for QT-interval prolongation are present. I(EY POI TT o Fluoroquinolones should be avoided in patients with o Guidelines recommend that tuberculosis screening be an aortic aneurysm or those at risk for an aortic aneu- repeated in persons with HIV when the CD4 cell count rysm unless no other treatment options are available. rises to 2OOl1tL.

guideline of the American Thoracic Society and Infectious Diseases Bibliography Society of America. Am J Respir Crit Care Med. 2019;200:e45-e67' [PMID: Gorelik E, Masarwa R, Perlman A, et aI. Fluoroquinolones and cardiovascu 315733501 doi:10.1164/rccm.2019O8-1581ST lar risk: A systematic review meta analysis and network meta analysis' Drug Saf. 2019 ;42:529 538. [PMID: 30368737] doi:10'1007is 40264-018- 0751-2 Item 73 Answer: B Ed ucationa I O biective : Prevent fluoroquinolone adverse effects. Item 74 Answer: D This patient should undergo electrocardiography before cip- Educational Obiective: Screen for tuberculosis in an rofloxacin is initiated (Option B). Fluoroquinolones have been individual with advanced HIV and recovering CD4 cell associated with QT-interval prolongation. Patients particu- count. larly at risk are those with hypokalemia, hypomagnesemia, The interferon y release assay (IGRA) should be repeated and concomitant use of other drugs that cause QT-interval (Option D). This patient has had an excellent response to J prolongation (e.g., macrolides, azoles, amiodarone). Elec- his antiretroviral therapy (ART), with a dramatic reduction ut trocardiography and corrected QT measurement should be E in his HIV RNA and improvement in his CD4 cell count. .D rl performed before starting a fluoroquinolone in patients at The original tuberculosis screening was performed at the UI q, increased risk and periodically thereafter for the duration of same time as his initial HIV diagnosis, which resulted in J treatment. In the absence of additional risk factors, routine a negative IGRA. His previous incarceration places him at EL a'l electrocardiography screening is not necessary. Additional risk for tuberculosis; if he would have acquired tuberculosis rl r-t adverse effects of fluoroquinolones include increased risk of previously, he is also at high risk for progression considering ll-a tendinitis and tendon rupture (most commonly the Achilles his HIV infection. Guidelines recommend that tuberculosis E .D tendon) ; hypog$cemia or hyperglycemia; peripheral neurop- screening be repeated in persons with HIV when the CD4 cell la athy; and neurologic side effects such as delirium, agitation, count rises to 2OOl1tL, especially if previous testing was nega nervousness, and memory impairment. Fluoroquinolones tive and the patient has signiflcant risk factors. also carry a two-fold increased risk of rupture and dissection Mycobacterium auium complex (MAC) infections can of the sorta; they should be avoided in persons who have an be seen in persons with advanced HIV. However, with a aortic aneurysm or are at risk for an aortic aneurysm (e.g., pretreatment CD4 cell count of more than 50/prl and a older adults and those with peripheral atherosclerotic vas- remarkable increase following effective ART, the risk for cular diseases, uncontrolled hypertension, certain genetic MAC related infection is low. Performing acid-fast bacilli conditions) unless no other treatment options are available. blood cultures for evaluation of disseminated MAC infection Mild elevations of aminotransferase levels are an has little to no utility in this patient (Option A). observed effect of fluoroquinolones, but severe liver disease Starting active tuberculosis treatment without conflr- and liver failure are rare. Obtaining pretreatment amino- matory testing for tuberculosis infection is not appropriate transferase levels (Option A) is unnecessary. Statins are an and puts patients at risk for complications from a regimen example of a drug class for which pretreatment amino- with several adverse effects (Option B). transferase measurements are recommended. Similarly, initiating latent tuberculosis treatment The gastrointestinal eflects of fluoroquinolones (anorexia, without a flrm diagnosis would be inappropriate (Option nausea, vomiting, mild abdominal discomfort) do not include C). Although treatment regimens are effective, several pancreatitis, so monitoring the serum lipase level (Option C) (especially rifamycin based regimens) have signiflcant is unnecessar!; regardless, the serum lipase level would not interactions with tenofovir alafenamide and integrase be measured unless the patient had symptoms compatible inhibitors like bictegravir or dolutegravir. If a diagnosis with acute pancreatitis. of latent tuberculosis were established, then treatment Diminished visual acuity is not an adverse effect of fluor- would be provided with isoniazid for 6 to 9 months with oquinolone therapy, and visual acuity screening (Option D) continuation of current ART or a weekly isoniazid and is not necessary before therapy initiation. Changes in visual rifapentine-based regimen for 12 weeks with modiflcation acuity or red-green color blindness is a known adverse effect of his current single-tablet ART regimen. The decision to of treatment with ethambutol and requires visual acuity start latent tuberculosis management should not be made testing before starting the drug. without repeating the IGRA flrst. XEY POITTS Repeat screening for tuberculosis is indicated in this o Fluoroeuinolones are associated with QT-interval pro- patient with HIV and recovering CD4 cell count with the decision to initiate therapy informed by results; therefore, no Iongation, and baseline electrocardiography should be additional testing is not appropriate (Option E). performed and repeated during therapy if other risk factors for QT-interval prolongation are present. I(EY POI TT o Fluoroquinolones should be avoided in patients with o Guidelines recommend that tuberculosis screening be an aortic aneurysm or those at risk for an aortic aneu- repeated in persons with HIV when the CD4 cell count rysm unless no other treatment options are available. rises to 2OOl1tL. 176

Answers and Criti ques Bibliography Item 76 Answer: B Panel on Opportunistic Infections in HIV-lnfected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections Ed ucationa I Objective: Diagnose Epstein-Barr virus- in HIV infected adults and adolescents: recommendations from the related posttransplant lymphoproliferative disorder. Centers for Disease Control and prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated lune 26,2019. Available at https://aidsinfo. The most likely diagnosis in this patient is posttransplant nih. gov/guidelines/ html/4 /adult and-adolescent-opportunistic_ lymphoproliferative disorder (PTLD) secondary to Epstein-Barr infection/ 392 /whats-new virus (EBV) infection (Option B). She is immunocompromised and at very high risk for EBV-related complications (donor and recipient EBV and cytomegalovirus mismatch at the time of Item 75 Answer: C transplantation, recent intensiflcation of immunosuppression). Educational Objective: Diagnose West Nile encephalitis. Her history of weight loss and presence of a mediastinal mass on imaging is also worrisome for malignancy. It is likely that The cerebrospinal fluid (CSF) test most likely to conflrm she acquired primary EBV infection from the donated heart in vt the diagnosis is a West Nile virus (WNV) IgM measurement (l, (Option C) because WNV encephalitis is most likely in this the flrst year after transplantation, which may have presented I J

Bibliography Item 76 Answer: B Panel on Opportunistic Infections in HIV-lnfected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections Ed ucationa I Objective: Diagnose Epstein-Barr virus- in HIV infected adults and adolescents: recommendations from the related posttransplant lymphoproliferative disorder. Centers for Disease Control and prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated lune 26,2019. Available at https://aidsinfo. The most likely diagnosis in this patient is posttransplant nih. gov/guidelines/ html/4 /adult and-adolescent-opportunistic_ lymphoproliferative disorder (PTLD) secondary to Epstein-Barr infection/ 392 /whats-new virus (EBV) infection (Option B). She is immunocompromised and at very high risk for EBV-related complications (donor and recipient EBV and cytomegalovirus mismatch at the time of Item 75 Answer: C transplantation, recent intensiflcation of immunosuppression). Educational Objective: Diagnose West Nile encephalitis. Her history of weight loss and presence of a mediastinal mass on imaging is also worrisome for malignancy. It is likely that The cerebrospinal fluid (CSF) test most likely to conflrm she acquired primary EBV infection from the donated heart in vt the diagnosis is a West Nile virus (WNV) IgM measurement (l, (Option C) because WNV encephalitis is most likely in this the flrst year after transplantation, which may have presented I J as a mononucleosis-like syndrome. Afterward, intensiflcation ET a- patient. WNV is an arbovirus transmitted by mosquitoes P of ongoing immunosuppression would be the most signiflcant L and occurs between June and October in endemic areas. (J factor in development of PTLD related to EBV infection. A sub- 'E WNV can present with a febrile illness, meningitis, myelitis, E stantial increase in the EBV viral load supports the diagnosis, r! or encephalitis. Older adult patients are at higher risk of ta which can be confirmed with tissue biopsy of the mediastinal L encephalitis and have a higher mortality. MRI of the brain o, mass or involved lymph nodes. Management of EBV related in this patient is classic, with basal ganglia involvement that complications, including PTLD, focuses primarily on reducing ta = ? can account for tremors, parkinsonism, and myoclonus. immunosuppression; antiviral therapy is not effective. Late- - WNV can also cause a maculopapular rash. The CSF proflle onset PTLD can also be EBV negative. usually shows a mild lymphocytic pleocytosis, a normal Adenovirus infections can cause signiflcant morbidity glucose level, and mildly elevated protein level. The diagno- and mortality in organ transplant recipients and could cause sis is made with a WNV IgM in the CSF or the serum. WNV disseminated infections involving not only the grafted organ polymerase chain reaction (PCR) (Option D) is not sensitive but also lungs and liver in patients with heart transplants. because the viremia is usually cleared by the time of clinical However, this patient's presentation of a mediastinal mass is presentation. No vaccine is available for WNV encephalitis, not typical for adenovirus infection (Option A). and treatment is supportive. Escherichia coli inf'ection is unlikely with this patient's Herpes simplex virus (HSV) type 1is the most common symptoms (Option C). A more acute onset with high fevers cause of sporadic encephalitis. The standard test for diag- and an obvious genitourinary or gastrointestinal focus would nosis is the HSV PCR (Option B). HSV IgM measurement point more clearly toward E. coli as the cause. (Option A) is not helpful in the early diagnosis of HSV The risk of other opportunistic infections, including Pneu- encephalitis. Viral antibody titers do rise signiflcantly over mocystis jirouecii also increases after transplantation (Option the course of the illness but typically do not become positive D). Often, Pneumocystis prophylaxis is discontinued 1 year until 10 to 14 days after illness onset and are therefore not after transplantation, but this timeline is reset in episodes of helpful in directing early, appropriate therapy or allowing rejection and intensiflcation of immunosuppression. Patients for discontinuation of unnecessary therapy. HSV encephali- with Pneumocystis infection most commonly present with tis should be empirically treated with intravenous acyclovir fever, cough, dyspnea, and diffuse, bilateral interstitial infll- in all patients while awaiting results of the CSF HSV PCR. A trates. This patient's presentation is unusual for Pneumocystis delay in acyclovir initiation is associated with adverse clin- infection, and the likelihood of this pathogen would be low ical outcomes. The MRI typically shows unilateral temporal with ongoing trimethoprim-sulfamethoxazole prophylaxis. lobe enhancement rather than basal ganglia involvement. KEY POIl{IS KEY POIilT5 . Episodes of organ rejection with intensified immuno- o West Nile virus can cause encephalitis presenting with suppression put patients at higher risk for posttrans- a febrile illness, tremors, parkinsonism, myoclonus, plant infections. and a maculopapular rash; MRI showing basal ganglia . Nonspecific symptoms such fever, weight loss, and involvement is classic. fatigue can be the initial presentation of Epstein-Barr . The diagnosis of West Nile virus encephalitis is made virus relate d po sttran splant lymphoproliferative with measurement of IgM in the cerebrospinal fluid or disorder. the serum.

as a mononucleosis-like syndrome. Afterward, intensiflcation ET a- patient. WNV is an arbovirus transmitted by mosquitoes P of ongoing immunosuppression would be the most signiflcant L and occurs between June and October in endemic areas. (J factor in development of PTLD related to EBV infection. A sub- 'E WNV can present with a febrile illness, meningitis, myelitis, E stantial increase in the EBV viral load supports the diagnosis, r! or encephalitis. Older adult patients are at higher risk of ta which can be confirmed with tissue biopsy of the mediastinal L encephalitis and have a higher mortality. MRI of the brain o, mass or involved lymph nodes. Management of EBV related in this patient is classic, with basal ganglia involvement that complications, including PTLD, focuses primarily on reducing ta = ? can account for tremors, parkinsonism, and myoclonus. immunosuppression; antiviral therapy is not effective. Late- - WNV can also cause a maculopapular rash. The CSF proflle onset PTLD can also be EBV negative. usually shows a mild lymphocytic pleocytosis, a normal Adenovirus infections can cause signiflcant morbidity glucose level, and mildly elevated protein level. The diagno- and mortality in organ transplant recipients and could cause sis is made with a WNV IgM in the CSF or the serum. WNV disseminated infections involving not only the grafted organ polymerase chain reaction (PCR) (Option D) is not sensitive but also lungs and liver in patients with heart transplants. because the viremia is usually cleared by the time of clinical However, this patient's presentation of a mediastinal mass is presentation. No vaccine is available for WNV encephalitis, not typical for adenovirus infection (Option A). and treatment is supportive. Escherichia coli inf'ection is unlikely with this patient's Herpes simplex virus (HSV) type 1is the most common symptoms (Option C). A more acute onset with high fevers cause of sporadic encephalitis. The standard test for diag- and an obvious genitourinary or gastrointestinal focus would nosis is the HSV PCR (Option B). HSV IgM measurement point more clearly toward E. coli as the cause. (Option A) is not helpful in the early diagnosis of HSV The risk of other opportunistic infections, including Pneu- encephalitis. Viral antibody titers do rise signiflcantly over mocystis jirouecii also increases after transplantation (Option the course of the illness but typically do not become positive D). Often, Pneumocystis prophylaxis is discontinued 1 year until 10 to 14 days after illness onset and are therefore not after transplantation, but this timeline is reset in episodes of helpful in directing early, appropriate therapy or allowing rejection and intensiflcation of immunosuppression. Patients for discontinuation of unnecessary therapy. HSV encephali- with Pneumocystis infection most commonly present with tis should be empirically treated with intravenous acyclovir fever, cough, dyspnea, and diffuse, bilateral interstitial infll- in all patients while awaiting results of the CSF HSV PCR. A trates. This patient's presentation is unusual for Pneumocystis delay in acyclovir initiation is associated with adverse clin- infection, and the likelihood of this pathogen would be low ical outcomes. The MRI typically shows unilateral temporal with ongoing trimethoprim-sulfamethoxazole prophylaxis. lobe enhancement rather than basal ganglia involvement. KEY POIl{IS KEY POIilT5 . Episodes of organ rejection with intensified immuno- o West Nile virus can cause encephalitis presenting with suppression put patients at higher risk for posttrans- a febrile illness, tremors, parkinsonism, myoclonus, plant infections. and a maculopapular rash; MRI showing basal ganglia . Nonspecific symptoms such fever, weight loss, and involvement is classic. fatigue can be the initial presentation of Epstein-Barr . The diagnosis of West Nile virus encephalitis is made virus relate d po sttran splant lymphoproliferative with measurement of IgM in the cerebrospinal fluid or disorder. the serum. Bibliography Bibliography Hansen MA, Samannodi MS, Castelblanco RL, et al. Clinical epidemiolory, Dierickr D, Habermann TM. Post-transplantation lymphoproliferative dis- risk factors, and outcomes of encephalitis in older adults. Clin Infect Dis. orders in adults. N Engl J Med. 2018;378:549-562. [PMID:29474277] '2O2O :7O :2377-2385. IPMID : 3129 4449] doi:10.1093/cid/ciz635 doi : 1 O. 1056 /NEJMralT O2693

Bibliography Bibliography Hansen MA, Samannodi MS, Castelblanco RL, et al. Clinical epidemiolory, Dierickr D, Habermann TM. Post-transplantation lymphoproliferative dis- risk factors, and outcomes of encephalitis in older adults. Clin Infect Dis. orders in adults. N Engl J Med. 2018;378:549-562. [PMID:29474277] '2O2O :7O :2377-2385. IPMID : 3129 4449] doi:10.1093/cid/ciz635 doi : 1 O. 1056 /NEJMralT O2693 177

Answers and Critiques Item 77 Answer: D Bibliography tr Educational Obiective: Manage a brain abscess. Sonneville R. Ruimy R, Benzonana N, et al; ESCMID Study Group for Infectious Diseases of the Brain (ESGIB)' An update on bacterial brain abscess in immunocompetent patients' Clin Microbiol Inf'ect' 2017:23: 'lhe most appropriate next step filr this patient is to 674- 620. IPMID: 28501669] doi:10.1016 /j.cmi.2017.05'004

Item 77 Answer: D Bibliography tr Educational Obiective: Manage a brain abscess. Sonneville R. Ruimy R, Benzonana N, et al; ESCMID Study Group for Infectious Diseases of the Brain (ESGIB)' An update on bacterial brain abscess in immunocompetent patients' Clin Microbiol Inf'ect' 2017:23: 'lhe most appropriate next step filr this patient is to 674- 620. IPMID: 28501669] doi:10.1016 /j.cmi.2017.05'004 perfilrm a stereotactic brain aspiration (Option D) fbr a culture to guide antibiotic therapy. This patient has a brain abscess. Brain abscesses in imnrunocompetent Answer: C Item 78 patients are mait-tly caused by b:rcteria that enter the brain through contiguous spread (e.g., fbllowing otitis, Educational Obiective : Treat latent tuberculosis mastoiditis, sinusitis. neurosurgical procedures, or cranial infection in an immunocompetent person. trauma) or hematogellous disseurination (e.g., inf'ective Treatment with isoniazid and rifampin daily for 3 months endocarditis, bacterentia from a dentitl source). Head is most appropriate for this patient (Option C). She has ache is the most colnnlon presetrting sytnpt<lm. with the a tuberculin skin test (TST) reaction greater than 15 mm, J gr classic triad (f'ever, headache, fbcal neurologic deficit) seen indicating a positive result. However, she has no signs of in only approximertely 2O'l, of'patients. 'lhe nrrlst conlfilon active tuberculosis infection (normal chest radiograph and = .D -l bacteria causing brain abscesses are streptoctlcci (e.g.. l,| no clinical flndings), so treatment for latent tuberculosis o, Streptococcus ntilleri). Stophylococcus oLlreus, Entero infection (U[BI) should be initiated. Short-course treatment a J bacteriaceae, and anaerclbes. 'lhe diagnosis is usually regimens with rifamycins are recommended over longer n rl nrade by CT or MRI with contrast. Aspiration is especially (O- to 9 month) courses. In persons without HIV infection, olt recomnlended il the brain abscess is larger than 2.5 cm. other preferred regimens include isoniazid and rifapentine ll1- -a 'lhe yield of blood cultures is low (around'25"/,,): even with -o rh a positive blood culture, aspiratiotr should be perfbnned once weekly for 3 months or rifampin daily for 4 months. Alternatively, daily isoniazid alone for 6 or 9 months is lbr a lirrge abscess. now considered a second-line treatment option; it carries a Treatment with intravenous penicillin and n-retronida higher toxicity risk and lower completion rate than short- zole (Option A) is an appropriate ernpiric ar-rtibiotic selection course regimens. Short-course treatment regimens are also fbr brain abscess secondary to irn odontogenic inf'ectiorr. recommended for LIBI in patients with HIV infection; these llowever, the source of'this patient's inf'ection is rnost likely include isoniazid and rifapentine once weekly for 3 months mastoiditis, and empiric antibiotic treatment with rnetro or isoniazid plus rifampin daily for 3 months in patients nidazole plus a third-generation cephalosporin following who are not taking antiretroviral therapy that interacts with abscess aspiration and Grarn stain, while waiting fbr culture rifapentine. results, would be more appropriate. Monotherapy with isoniazid can be offered to patients lntravenous vancolnycin (Option B) would be an appro with LTBI and HIV; however, monotherapy regimens priate empiric antibiotic selection fcrr a patient with a brain (Option A, B) are considered alternatives for patients who abscess and evidence of endocarditis or intrirvenous drug are unable to take rifapentine or rifampin. Short-course use. However. these predisposing factors are not present and combination therapy is as effective as longer duration ther- the best first management step is abscess aspiratior-r. Gram apy with isoniazid and is associated with higher treatment stain, and culture. completion rates and less toxicity. Performing a lumbar pur.rctr-rre (Option C) is not The four drug regimen of isoniazid, rifampin, pyr indicated because it could place the patient at risk fbr azinamide, and ethambutol (Option D) is the standard herniationr additionally. the yield of'a cerebrospinal fluid (CSF) culture is low. 'l'he CSF'cr-rlture can be positive if for active tuberculosis treatment. This patient does not have active tuberculosis and does not require four drug the abscess ruptures into the verrtriclesl this wcluld be an treatment that will be unnecessarily toxic for a patient indication fbr an emergent craniotonry and ventricular with LTBI. lavage. XEY POITTg I(EY POI ilTS o Short-course dual therapy with isoniazid and rifampin . Brain abscesses in immunocompetent patients are or rifapentine is the preferred treatment for patients mainly caused by bacteria that enter the brain through with latent tuberculosis infection. contiguous spread (e.g., following otitis, mastoiditis, . Daily isoniazid monotherapy for 6 or 9 months can be sinusitis, neurosurgical procedures, or cranial trauma) recommended for patients with latent tuberculosis who or hematogenous dissemination (e.g., infective endo- cannot take rifapentine or rifampin. carditis, bacteremia from a dental source). o Empiric antibiotic therapy for brain abscess should be guided by the source of infection and Gram stain, and Bibliography Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent directed therapy should be guided by culture results tuberculosis infection: Recommendations from the National Tuberculosis whenever possible. Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020; 69(1) :l -11. [pttltD' 32053584] doi:10. 15585/mmwr.116901al

perfilrm a stereotactic brain aspiration (Option D) fbr a culture to guide antibiotic therapy. This patient has a brain abscess. Brain abscesses in imnrunocompetent Answer: C Item 78 patients are mait-tly caused by b:rcteria that enter the brain through contiguous spread (e.g., fbllowing otitis, Educational Obiective : Treat latent tuberculosis mastoiditis, sinusitis. neurosurgical procedures, or cranial infection in an immunocompetent person. trauma) or hematogellous disseurination (e.g., inf'ective Treatment with isoniazid and rifampin daily for 3 months endocarditis, bacterentia from a dentitl source). Head is most appropriate for this patient (Option C). She has ache is the most colnnlon presetrting sytnpt<lm. with the a tuberculin skin test (TST) reaction greater than 15 mm, J gr classic triad (f'ever, headache, fbcal neurologic deficit) seen indicating a positive result. However, she has no signs of in only approximertely 2O'l, of'patients. 'lhe nrrlst conlfilon active tuberculosis infection (normal chest radiograph and = .D -l bacteria causing brain abscesses are streptoctlcci (e.g.. l,| no clinical flndings), so treatment for latent tuberculosis o, Streptococcus ntilleri). Stophylococcus oLlreus, Entero infection (U[BI) should be initiated. Short-course treatment a J bacteriaceae, and anaerclbes. 'lhe diagnosis is usually regimens with rifamycins are recommended over longer n rl nrade by CT or MRI with contrast. Aspiration is especially (O- to 9 month) courses. In persons without HIV infection, olt recomnlended il the brain abscess is larger than 2.5 cm. other preferred regimens include isoniazid and rifapentine ll1- -a 'lhe yield of blood cultures is low (around'25"/,,): even with -o rh a positive blood culture, aspiratiotr should be perfbnned once weekly for 3 months or rifampin daily for 4 months. Alternatively, daily isoniazid alone for 6 or 9 months is lbr a lirrge abscess. now considered a second-line treatment option; it carries a Treatment with intravenous penicillin and n-retronida higher toxicity risk and lower completion rate than short- zole (Option A) is an appropriate ernpiric ar-rtibiotic selection course regimens. Short-course treatment regimens are also fbr brain abscess secondary to irn odontogenic inf'ectiorr. recommended for LIBI in patients with HIV infection; these llowever, the source of'this patient's inf'ection is rnost likely include isoniazid and rifapentine once weekly for 3 months mastoiditis, and empiric antibiotic treatment with rnetro or isoniazid plus rifampin daily for 3 months in patients nidazole plus a third-generation cephalosporin following who are not taking antiretroviral therapy that interacts with abscess aspiration and Grarn stain, while waiting fbr culture rifapentine. results, would be more appropriate. Monotherapy with isoniazid can be offered to patients lntravenous vancolnycin (Option B) would be an appro with LTBI and HIV; however, monotherapy regimens priate empiric antibiotic selection fcrr a patient with a brain (Option A, B) are considered alternatives for patients who abscess and evidence of endocarditis or intrirvenous drug are unable to take rifapentine or rifampin. Short-course use. However. these predisposing factors are not present and combination therapy is as effective as longer duration ther- the best first management step is abscess aspiratior-r. Gram apy with isoniazid and is associated with higher treatment stain, and culture. completion rates and less toxicity. Performing a lumbar pur.rctr-rre (Option C) is not The four drug regimen of isoniazid, rifampin, pyr indicated because it could place the patient at risk fbr azinamide, and ethambutol (Option D) is the standard herniationr additionally. the yield of'a cerebrospinal fluid (CSF) culture is low. 'l'he CSF'cr-rlture can be positive if for active tuberculosis treatment. This patient does not have active tuberculosis and does not require four drug the abscess ruptures into the verrtriclesl this wcluld be an treatment that will be unnecessarily toxic for a patient indication fbr an emergent craniotonry and ventricular with LTBI. lavage. XEY POITTg I(EY POI ilTS o Short-course dual therapy with isoniazid and rifampin . Brain abscesses in immunocompetent patients are or rifapentine is the preferred treatment for patients mainly caused by bacteria that enter the brain through with latent tuberculosis infection. contiguous spread (e.g., following otitis, mastoiditis, . Daily isoniazid monotherapy for 6 or 9 months can be sinusitis, neurosurgical procedures, or cranial trauma) recommended for patients with latent tuberculosis who or hematogenous dissemination (e.g., infective endo- cannot take rifapentine or rifampin. carditis, bacteremia from a dental source). o Empiric antibiotic therapy for brain abscess should be guided by the source of infection and Gram stain, and Bibliography Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent directed therapy should be guided by culture results tuberculosis infection: Recommendations from the National Tuberculosis whenever possible. Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020; 69(1) :l -11. [pttltD' 32053584] doi:10. 15585/mmwr.116901al 178

Answers and Critiques Item 79 Answer: C whicl-r cerebrospir-iai fluicl (CSF') Granr stiiin i.iiir,l culturcs i.l-r, Educational Objective: Diagnose osteomyelitis in a negatire. Viral n-reningitis ustiaily preserrts witlt a milcl ltleo diabetic foot infection. cytosis (50-i000r'uL [50,1000 x i0(',1.1). nri]clly elevatcd CSI:' protein level (<200 rngrdl IZOOO rrrg,l.l). ancl a normal CSl. MRI should be performed to evaluate for the extent of infec- glucose lelel (>45 nrgrdL [2.5 l:rnroi,i-j). ['atielrts r,rritlt viral tion (Option C), including possible bone involvement. Radi tteningitis may present r,vith a neutrophilic' plcocytosis in ography is recommended for all patients with diabetes with tlre frrst 21to 48 hours, n{rich typicalll,' becoitres lvnrphocvtic new foot infections to assess for soft tissue gas, foreign body, predominant. Most patients l-rilve tyiticll meningitis syntlt and bony involvement. However, bony abnormalities may not torns such as tbver. nuchal rigidity ireadaclte. lncl ltlrotoltho appear for 2 or more weeks after onset of infection. Although bia. HS\,'-2 is more conrnronlv :rssociuted lvith nreningitis. no bone is visible in the ulcer base, and the metal probe-to- occllrs year round" and is the nrost comnlon c:.luse of'rccur bone test is negative (positive predictive value of nearly 90% rent meningitis (recurrent benign lymphoc_ytic rrreningiiis). for osteomyelitis), the latter only has a negative predictive Outcomes for HS\'2 meningitis :lre gener;ill-y f:rvorable lvitir UI a, value of about 60'1,. Erythrocyte sedimentation rates greater or-rt the need fbr acyclovir therapyi - than 70 mm/h and ulcers larger than 2 x 2 cm are associated with an increased likelihood of osteomyelitis. This patient Enteroviruses (Option A) are the most cornnron cause o1' *lr r a- viralmeningitis but usually pi'esent betr,r,een Muy irncl Novenr h L' also has a leukocytosis, although up to two thirds of patients ber in the Western her-nisphere. r,r,itl-r synlptonls inch-rcling ?g with osteomyelitis may have a normal leukocyte count. In headache, fever, nuchal rigiditli photophobiir. nlusel, vonr r! patients with highly suspected osteomyelitis and a normal iting, m1,'algia, pharyngitis. nracukrptrlrular rasl-r. and cough. UI I radiograph, MRI with and without intravenous contrast is Presentation in the lt inter m;rkes this an unlikely clluse ol'this t 3 the most accurate imaging study for evaluating diabetic foot patient's iliness. CSF polymemse chain reactiorr stuclir:s nray UI C osteomyelitis. In addition, it can better delineate the soft tis- be used to rapidly diagnose I'{SV and enterovims nreningilis. q sue involvement, including evidence of necrosis, abscess, and HSV-t (Option B) is the musl conrfiron c;ruse of'sporadicr sinus tracts, allowing for better decision making regarding encephalitis in the United States and can occur ycar r<lur.rcl. potential surgical intervention. HSV 1 encephalitis presents with f'ever, seizures, alterccl If MRI cannot be performed, then a CT with intravenous mental status. and focal neurologic deficits. contrast (Option A), which is neither as sensitive nor speciflc West Nile virus (Option D) is a mosquito borne illnr-'ss for acute osteomyelitis, is an alternative. If neither MRI nor that may also have a similar ciinical presentation ltrd OSI; CT can be performed (e.g., presence of metal hardware) a profile as I{S\L2 meningitis, but it occllrs between Jutre :incl nuclear medicine study such as a tagged leukocyte scan or October. West Nile virus nray also prc'seut r.t,ith nretringoclt three-phase bone scan (Option B, D) may be helpful. Com- cephalitis or as all isolated rnyelitis. In its ntc.rst severe Ibrnt, bining a labeled leukocyte scan with a three-phase bone inf'ection of the anterior horn cells catl cause a symrnetric or scan can improve accuracy of the nuclear medicine testing in asyrnmetric flaccid paralysis, analogous to tlrat previousl-y diagnosing osteomyelitis, but it is time consuming, expen- seen u,ith poiio. 'ihe diagnosis can be confirt-ned tltrough sive, and has lower speciflcity than MRI. ider-itification of'the lgM antibody itt CSIr. t(tv P0tt{Ts rEY POIilT5 o Radiography is recommended for all patients with . Viral meningitis is the most common cause of "aseptic" diabetes and new foot infections. meningitis, with negative cerebrospinal fluid (CSF) o In patients with suspected osteomyelitis and a normal Gram stain and cultures, slightly increased leukocyte plain radiograph, MRI with and without intravenous count, slightly elevated CSF protein level, and normal contrast is recommended in evaluating diabetic foot CSF glucose level.

Item 79 Answer: C whicl-r cerebrospir-iai fluicl (CSF') Granr stiiin i.iiir,l culturcs i.l-r, Educational Objective: Diagnose osteomyelitis in a negatire. Viral n-reningitis ustiaily preserrts witlt a milcl ltleo diabetic foot infection. cytosis (50-i000r'uL [50,1000 x i0(',1.1). nri]clly elevatcd CSI:' protein level (<200 rngrdl IZOOO rrrg,l.l). ancl a normal CSl. MRI should be performed to evaluate for the extent of infec- glucose lelel (>45 nrgrdL [2.5 l:rnroi,i-j). ['atielrts r,rritlt viral tion (Option C), including possible bone involvement. Radi tteningitis may present r,vith a neutrophilic' plcocytosis in ography is recommended for all patients with diabetes with tlre frrst 21to 48 hours, n{rich typicalll,' becoitres lvnrphocvtic new foot infections to assess for soft tissue gas, foreign body, predominant. Most patients l-rilve tyiticll meningitis syntlt and bony involvement. However, bony abnormalities may not torns such as tbver. nuchal rigidity ireadaclte. lncl ltlrotoltho appear for 2 or more weeks after onset of infection. Although bia. HS\,'-2 is more conrnronlv :rssociuted lvith nreningitis. no bone is visible in the ulcer base, and the metal probe-to- occllrs year round" and is the nrost comnlon c:.luse of'rccur bone test is negative (positive predictive value of nearly 90% rent meningitis (recurrent benign lymphoc_ytic rrreningiiis). for osteomyelitis), the latter only has a negative predictive Outcomes for HS\'2 meningitis :lre gener;ill-y f:rvorable lvitir UI a, value of about 60'1,. Erythrocyte sedimentation rates greater or-rt the need fbr acyclovir therapyi - than 70 mm/h and ulcers larger than 2 x 2 cm are associated with an increased likelihood of osteomyelitis. This patient Enteroviruses (Option A) are the most cornnron cause o1' *lr r a- viralmeningitis but usually pi'esent betr,r,een Muy irncl Novenr h L' also has a leukocytosis, although up to two thirds of patients ber in the Western her-nisphere. r,r,itl-r synlptonls inch-rcling ?g with osteomyelitis may have a normal leukocyte count. In headache, fever, nuchal rigiditli photophobiir. nlusel, vonr r! patients with highly suspected osteomyelitis and a normal iting, m1,'algia, pharyngitis. nracukrptrlrular rasl-r. and cough. UI I radiograph, MRI with and without intravenous contrast is Presentation in the lt inter m;rkes this an unlikely clluse ol'this t 3 the most accurate imaging study for evaluating diabetic foot patient's iliness. CSF polymemse chain reactiorr stuclir:s nray UI C osteomyelitis. In addition, it can better delineate the soft tis- be used to rapidly diagnose I'{SV and enterovims nreningilis. q sue involvement, including evidence of necrosis, abscess, and HSV-t (Option B) is the musl conrfiron c;ruse of'sporadicr sinus tracts, allowing for better decision making regarding encephalitis in the United States and can occur ycar r<lur.rcl. potential surgical intervention. HSV 1 encephalitis presents with f'ever, seizures, alterccl If MRI cannot be performed, then a CT with intravenous mental status. and focal neurologic deficits. contrast (Option A), which is neither as sensitive nor speciflc West Nile virus (Option D) is a mosquito borne illnr-'ss for acute osteomyelitis, is an alternative. If neither MRI nor that may also have a similar ciinical presentation ltrd OSI; CT can be performed (e.g., presence of metal hardware) a profile as I{S\L2 meningitis, but it occllrs between Jutre :incl nuclear medicine study such as a tagged leukocyte scan or October. West Nile virus nray also prc'seut r.t,ith nretringoclt three-phase bone scan (Option B, D) may be helpful. Com- cephalitis or as all isolated rnyelitis. In its ntc.rst severe Ibrnt, bining a labeled leukocyte scan with a three-phase bone inf'ection of the anterior horn cells catl cause a symrnetric or scan can improve accuracy of the nuclear medicine testing in asyrnmetric flaccid paralysis, analogous to tlrat previousl-y diagnosing osteomyelitis, but it is time consuming, expen- seen u,ith poiio. 'ihe diagnosis can be confirt-ned tltrough sive, and has lower speciflcity than MRI. ider-itification of'the lgM antibody itt CSIr. t(tv P0tt{Ts rEY POIilT5 o Radiography is recommended for all patients with . Viral meningitis is the most common cause of "aseptic" diabetes and new foot infections. meningitis, with negative cerebrospinal fluid (CSF) o In patients with suspected osteomyelitis and a normal Gram stain and cultures, slightly increased leukocyte plain radiograph, MRI with and without intravenous count, slightly elevated CSF protein level, and normal contrast is recommended in evaluating diabetic foot CSF glucose level. osteomyelitis. o Herpes simplex virus type 2 is most commonly asso- ciated with meningitis, occurs year round, and is the Bibliography most common cause of recurrent meningitis. Lipsky BA, Berendt AR, Cornia PB, et al; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Bibliography Infect Dis. 2Ot2;54 :e132 23. [PM I D : ZZOtgZqZ) doi 10. 1 093 /cid/cis346 : Shukta B, Aguilera EA, Salazar L, et al. Aseptic meningitis in adults and children: Diagnostic and management challenges. J Clin Yirol. 201794 11 o - 114. [pl,tl O' zsso o doi: 10. 1 01 6 /i .icv.2o77 07 ot 6 . .

osteomyelitis. o Herpes simplex virus type 2 is most commonly asso- ciated with meningitis, occurs year round, and is the Bibliography most common cause of recurrent meningitis. Lipsky BA, Berendt AR, Cornia PB, et al; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Bibliography Infect Dis. 2Ot2;54 :e132 23. [PM I D : ZZOtgZqZ) doi 10. 1 093 /cid/cis346 : Shukta B, Aguilera EA, Salazar L, et al. Aseptic meningitis in adults and children: Diagnostic and management challenges. J Clin Yirol. 201794 11 o - 114. [pl,tl O' zsso o doi: 10. 1 01 6 /i .icv.2o77 07 ot 6 . . 'zs] Item 80 Answer: C tr Educational Objective: Diagnose herpes simplex Item 81 Answer: D meningitis. Educational Objective: Diagnose Ramsay Hunt syndrome caused by herpes zoster infection. The rnost likely diagnosis in this patient is meningitis caused by herpes simplex virus (HSV) type 2 (Option C). Viral nlen- The most likely diagnosis for this older man is Ramsay Hunt ingitis is the most common cause clf "aseptic" meningitis, in syndrome (herpes zoster oticus) caused by varicella-zoster 179

Answers and Critiques virus (Option D). Ramsay Hunt syndrome is characterized Item 82 Answer: C by peripheral facial nerve palsy (cranial nerve VII) accom- Ed ucationa I Objective: Prevent catheter-associated panied by an erythematous vesicular rash on the ear (zoster urinary tract infection. oticus) or lesions in the mouth. In this patient, the oral flnd- ings include mucosal erosions conflned to the right side of Removing this patient's indwelling urinary catheter is the the tongue. Patients may have tinnitus, hearing loss, nausea, most appropriate management (Option C). Patients who vomiting, vertigo, and nystagmus that can be explained by are female and older than 50 years are at increased risk for the involvement of the geniculate ganglion to the vestibulo- catheter-associated urinary tract infection (CAUTI); a serum cochlear nerve within the bony facial canal. Differentiating creatinine level greater than 2 mgldL (177 pmolll) in this between a peripheral and a central facial palsy is crucial population is also a risk factor. Without an accepted indica- because the latter is associated with an intracranial lesion. tion for an indwelling urinary catheter, it should be removed. A peripheral facial palsy involves the whole side of the face, Accurate monitoring of urine output in a critically ill patient including the forehead, as in this patient. The differential is an accepted indication, but this patient is not critically ill. J UI diagnosis of an irrfectious cause of peripheral facial nerve Her fluid status can be assessed by other means (e.g., weight), (D (Bell) palsy includes herpes simplex virus type 1, Lyme or the urine may be collected in another manner to measure -=qt ur disease caused by Borrelia burgdorferi, and varicella-zoster output. Her history of urinary incontinence alone is also not virus. an indication for an indwelling urinary catheter. Indwelling J EL Infection of neurologic tissue occurs in approximately urinary catheters may be used in the management of stage n - 15%, of untreated patients with Lyme disease (Option A). III or IV or unstageable perineal or sacral pressure ulcers in dt patients who are incontinent. External catheters (e,g., con- -a Aseptic meningitis, peripheral nerve facial palsy (unilat- -cl -a

virus (Option D). Ramsay Hunt syndrome is characterized Item 82 Answer: C by peripheral facial nerve palsy (cranial nerve VII) accom- Ed ucationa I Objective: Prevent catheter-associated panied by an erythematous vesicular rash on the ear (zoster urinary tract infection. oticus) or lesions in the mouth. In this patient, the oral flnd- ings include mucosal erosions conflned to the right side of Removing this patient's indwelling urinary catheter is the the tongue. Patients may have tinnitus, hearing loss, nausea, most appropriate management (Option C). Patients who vomiting, vertigo, and nystagmus that can be explained by are female and older than 50 years are at increased risk for the involvement of the geniculate ganglion to the vestibulo- catheter-associated urinary tract infection (CAUTI); a serum cochlear nerve within the bony facial canal. Differentiating creatinine level greater than 2 mgldL (177 pmolll) in this between a peripheral and a central facial palsy is crucial population is also a risk factor. Without an accepted indica- because the latter is associated with an intracranial lesion. tion for an indwelling urinary catheter, it should be removed. A peripheral facial palsy involves the whole side of the face, Accurate monitoring of urine output in a critically ill patient including the forehead, as in this patient. The differential is an accepted indication, but this patient is not critically ill. J UI diagnosis of an irrfectious cause of peripheral facial nerve Her fluid status can be assessed by other means (e.g., weight), (D (Bell) palsy includes herpes simplex virus type 1, Lyme or the urine may be collected in another manner to measure -=qt ur disease caused by Borrelia burgdorferi, and varicella-zoster output. Her history of urinary incontinence alone is also not virus. an indication for an indwelling urinary catheter. Indwelling J EL Infection of neurologic tissue occurs in approximately urinary catheters may be used in the management of stage n - 15%, of untreated patients with Lyme disease (Option A). III or IV or unstageable perineal or sacral pressure ulcers in dt patients who are incontinent. External catheters (e,g., con- -a Aseptic meningitis, peripheral nerve facial palsy (unilat- -cl -a L eral or bilateral), and radiculopathy may be present in dom catheters for men or female external urinary collection .D tr isolation or associated with skin, musculoskeletal, or car- device with suction for women) can be used for patients diac flndings. When erythema migrans lesions are pres- with incontinence or increased urination (e.g., diuretic treat- ent, laboratory conflrmation is unnecessary. Otherwise, ment) when frequent toileting does not adequately address two tier serologic testing should be performed. However, the issue. Early removal of urinary catheters should be con- Lyme disease would not present with vesicular lesions of sidered whenever possible. the external ear and mucosal erosions conflned to half of In patients with short-term or long-term requirements the tongue. for an indwelling urinary catheter, administration of anti- Herpes simplex virus type 1 (Option B) is the most com- biotics such as trimethoprim-sulfamethoxazole (Option A) mon cause of Bell palsy, especially if the risk for Lyme disease is not indicated. Such therapy promotes the development of is low. It is not associated with a vesicular rash of the external resistant bacteria without improving patient care. ear with mucosal lesions involving half the tongue. Random urinalysis and urine culture is not helpful in Sarcoidosis (Option C) of the peripheral nerves can monitoring for CAUTI (Option B). Without symptoms, the cause cranial neuropathies, including peripheral facial results are likely to represent catheter colonization rather than nerve palsy. Facial palsy may be unilateral or bilateral. infection and may lead to inappropriate antibiotic use. Patients The diagnosis is most apparent in patients with known with indwelling urinary catheters should be assessed daily sarcoidosis who develop neurologic flndings but can be an for signs and symptoms of infection. If present, the catheter elusive diagnosis in patients without known sarcoidosis. should be removed. If symptoms persist after catheter removal, Sarcoidosis would not be associated with the combina the patient should be evaluated for urinary tract infection. tion of vesicular and crusted skin lesions and mucosal Antimicrobial-impregnated or antiseptic coated cath- erosions. eters (Option D) may decrease the incidence of asymptom- atic bacteriuria, but they have not been shown to decrease KEY POIT{T5 CAUTI or urinary catheter associated bloodstream infection o Ramsay Hunt syndrome is a peripheral facial nerve with short-term (<Z days) catheterization. Little informa- palsy caused by varicella-zoster virus and is charac- tion is available regarding beneflts with long term urinary terized by an erythematous vesicular rash on the ear catheters. (zoster oticus) or by lesions in the mouth, sometimes KEY POI l{T with tinnitus, hearing loss, nausea, vomiting, vertigo, or nystagmus. . Early removal of indwelling urinary catheters should be considered whenever possible, with use of external o The differential diagnosis of an infectious cause of catheters for patients with incontinence or increased peripheral facial nerve palsy includes herpes simplex urination when frequent toileting does not adequately virus type 1, Lyme disease, and varicella zoster virus. address the issue.

L eral or bilateral), and radiculopathy may be present in dom catheters for men or female external urinary collection .D tr isolation or associated with skin, musculoskeletal, or car- device with suction for women) can be used for patients diac flndings. When erythema migrans lesions are pres- with incontinence or increased urination (e.g., diuretic treat- ent, laboratory conflrmation is unnecessary. Otherwise, ment) when frequent toileting does not adequately address two tier serologic testing should be performed. However, the issue. Early removal of urinary catheters should be con- Lyme disease would not present with vesicular lesions of sidered whenever possible. the external ear and mucosal erosions conflned to half of In patients with short-term or long-term requirements the tongue. for an indwelling urinary catheter, administration of anti- Herpes simplex virus type 1 (Option B) is the most com- biotics such as trimethoprim-sulfamethoxazole (Option A) mon cause of Bell palsy, especially if the risk for Lyme disease is not indicated. Such therapy promotes the development of is low. It is not associated with a vesicular rash of the external resistant bacteria without improving patient care. ear with mucosal lesions involving half the tongue. Random urinalysis and urine culture is not helpful in Sarcoidosis (Option C) of the peripheral nerves can monitoring for CAUTI (Option B). Without symptoms, the cause cranial neuropathies, including peripheral facial results are likely to represent catheter colonization rather than nerve palsy. Facial palsy may be unilateral or bilateral. infection and may lead to inappropriate antibiotic use. Patients The diagnosis is most apparent in patients with known with indwelling urinary catheters should be assessed daily sarcoidosis who develop neurologic flndings but can be an for signs and symptoms of infection. If present, the catheter elusive diagnosis in patients without known sarcoidosis. should be removed. If symptoms persist after catheter removal, Sarcoidosis would not be associated with the combina the patient should be evaluated for urinary tract infection. tion of vesicular and crusted skin lesions and mucosal Antimicrobial-impregnated or antiseptic coated cath- erosions. eters (Option D) may decrease the incidence of asymptom- atic bacteriuria, but they have not been shown to decrease KEY POIT{T5 CAUTI or urinary catheter associated bloodstream infection o Ramsay Hunt syndrome is a peripheral facial nerve with short-term (<Z days) catheterization. Little informa- palsy caused by varicella-zoster virus and is charac- tion is available regarding beneflts with long term urinary terized by an erythematous vesicular rash on the ear catheters. (zoster oticus) or by lesions in the mouth, sometimes KEY POI l{T with tinnitus, hearing loss, nausea, vomiting, vertigo, or nystagmus. . Early removal of indwelling urinary catheters should be considered whenever possible, with use of external o The differential diagnosis of an infectious cause of catheters for patients with incontinence or increased peripheral facial nerve palsy includes herpes simplex urination when frequent toileting does not adequately virus type 1, Lyme disease, and varicella zoster virus. address the issue. Bibliography Bibliography Garro A, Nigrovic LE. Managing peripheral facial palsy. Ann Emerg Med. Shuman EK, Chenoweth CE. Urinary catheter associated infections. lnf'ect 2O7B;71 :678 OZ+. [PMID: ZgttOSSZ] doi:10. 101 6/j.annemergm ed.2Ot7. Dis Clin North Am. 2018;32:885 897. [PMID: SOZqUD) doi:10.1016/j. o8.039 idc.2018.07.002

Bibliography Bibliography Garro A, Nigrovic LE. Managing peripheral facial palsy. Ann Emerg Med. Shuman EK, Chenoweth CE. Urinary catheter associated infections. lnf'ect 2O7B;71 :678 OZ+. [PMID: ZgttOSSZ] doi:10. 101 6/j.annemergm ed.2Ot7. Dis Clin North Am. 2018;32:885 897. [PMID: SOZqUD) doi:10.1016/j. o8.039 idc.2018.07.002 180

Answers and Critiques Item 83 Answer: A Item 84 Answer: A Ed ucational Objective : Diagnose transfusion- Ed ucationa I O bjective : Diagnose invasive aspergillosis. tr transmitted babesiosis. This patient most likely has invasive pulmonary aspergillosis This patient with a febrile illness and hemolytic ane- (Option A). Aspergillus conidia initially invade pulmonary mia has transfusion-transmitted babesiosis, an erythro- blood vessels and cause distal infarction of tissue. Patients cyte infection caused by protozoan parasites in the genus generally have fever cough, chest pain, and hemoptysis at pre Babesia (Option A). Bobesia microti, the most com- sentation; this is usually seen in immunosuppressed patients mon cause of babesiosis, is primarily transmitted by the with neutropenia. Pulmonary infection involves infiltrates, black-legged deer tick, which is endemic in New England, thin-walled cavities, nodules, or wedge,shaped densities the mid-Atlantic, and the upper Midwest. Transfusion- resembling infarcts that may be seen on chest radiographs or transmitted disease is less common but likely underrecog- CT scans. In this person, the ground-glass appearance sur nized because infected blood products may be shipped rounding the nodule indicates hemorrhage into the surround- UI to regions where the disease does not normally occur. ing lung tissue (halo sign). In the appropriate clinical setting, o J

Item 83 Answer: A Item 84 Answer: A Ed ucational Objective : Diagnose transfusion- Ed ucationa I O bjective : Diagnose invasive aspergillosis. tr transmitted babesiosis. This patient most likely has invasive pulmonary aspergillosis This patient with a febrile illness and hemolytic ane- (Option A). Aspergillus conidia initially invade pulmonary mia has transfusion-transmitted babesiosis, an erythro- blood vessels and cause distal infarction of tissue. Patients cyte infection caused by protozoan parasites in the genus generally have fever cough, chest pain, and hemoptysis at pre Babesia (Option A). Bobesia microti, the most com- sentation; this is usually seen in immunosuppressed patients mon cause of babesiosis, is primarily transmitted by the with neutropenia. Pulmonary infection involves infiltrates, black-legged deer tick, which is endemic in New England, thin-walled cavities, nodules, or wedge,shaped densities the mid-Atlantic, and the upper Midwest. Transfusion- resembling infarcts that may be seen on chest radiographs or transmitted disease is less common but likely underrecog- CT scans. In this person, the ground-glass appearance sur nized because infected blood products may be shipped rounding the nodule indicates hemorrhage into the surround- UI to regions where the disease does not normally occur. ing lung tissue (halo sign). In the appropriate clinical setting, o J Furthermore, onset of illness can occur from 1 week the halo sign rnay indicate the presence of aspergillosis or a- y CT

Furthermore, onset of illness can occur from 1 week the halo sign rnay indicate the presence of aspergillosis or a- y CT to 6 months after transfusion (median onset 37 days), other angioinvasive fungal infection, including fusariosis and (, L obscuring the link between infection and receipt of blood mucormycosis. Other sites of involvement include the central products. Babesia infection can range from asymptom- nervous system, skin, and eye. Profound and prolonged neu- =, E .E atic to fulminant and potentially fatal disease, with older tropenia, especially in association with hematopoietic stem UI L adults, immunocompromised patients, and patients with cell transplantation or chemotherapy, is a risk factor for inva- o asplenia at highest risk for severe manifestations. Symp- sive aspergillosis: solid organ transplant recipients are also at ta s= toms are often nonspeciflc, with fever the most common. increased risk. Bronchoalveolar lavage (BAL) and biopsy are - Physical flndings are related to hemolysis and may include the most eft'ective methods for definitive diagnosis. In patients splenomegaly, hepatomegaly, and jaundice. Laboratory with pulmonary disease, the BAL and serum galactomannan abnormalities reflect the presence of hemolytic anemia; assay have excellent sensitivity and speciflcity (both >80'/,) in thrombocytopenia and elevated aminotransferase and patients with hematologic malignancies or following hemato- alkaline phosphatase levels are also common. Occasion poietic stem cell transplantation. ally, the diagnosis is made incidentally in asymptom- Candida crlbicons is a common cause of candidemia atic patients when intraerythrocytic rings are seen on a (Option B), but it rarely produces infections in the respira- peripheral blood smear. tory tract. Adclitionally, because most patients with acute Cytomegalovirus can be transmitted through trans- leukemia undergoing initial-induction chemotherapy are fusion and causes a mononucleosis like illness with receiving fluconazole prophylaxis, invasive candidiasis fever, absolute lymphocytosis, and thrombocytope- does not occur unless it is with a resistant species such as nia but does not commonly cause hemolytic anemia Candtda glabrata or Candida auris. (Option B). Cryptococc'us neoformons (Option C) cclmmonly causes Ehrlichiosis is a tick-borne infection that can rarely inf'ections in immunocompromised persons; however, this be transmitted through transfusion (Option C). Laboratory patient has no evidence of central nervous system involve abnormalities with ehrlichiosis include leukopenia, throm- ment, where this illness most commonly manifbsts. However, bocytopenia, and elevated aminotransferase levels ; hemoly- cryptococcal pneumonia can occur in immunocompromised sis is not seen with this infection. patients and typically presents with infiltrates, lymphade Leptospirosis can cause fever and cholestasis, but the nopathy, and mass lesions. Invasive aspergillosis is a more patient has no compatible history of travel, environmen common cause of'pneumonia in immunocompromised hosts, tal exposure, or animal exposure to support this diagnosis and the positive galactomannan assay supprtrts this diagnosis. (Option D). H istoplas ma capsulatu m (Option D) gene ral ly produces Parvovirus B-19 causes fever and anemia, but the asynrptomatic pulmonary inf'ection, but it is not typically anemia results from red cell aplasia rather than hemolysis associated with cavitary lung lesions in int'ected persons and (Option E). is not assc.rciated with a positive galactomannan assay.

to 6 months after transfusion (median onset 37 days), other angioinvasive fungal infection, including fusariosis and (, L obscuring the link between infection and receipt of blood mucormycosis. Other sites of involvement include the central products. Babesia infection can range from asymptom- nervous system, skin, and eye. Profound and prolonged neu- =, E .E atic to fulminant and potentially fatal disease, with older tropenia, especially in association with hematopoietic stem UI L adults, immunocompromised patients, and patients with cell transplantation or chemotherapy, is a risk factor for inva- o asplenia at highest risk for severe manifestations. Symp- sive aspergillosis: solid organ transplant recipients are also at ta s= toms are often nonspeciflc, with fever the most common. increased risk. Bronchoalveolar lavage (BAL) and biopsy are - Physical flndings are related to hemolysis and may include the most eft'ective methods for definitive diagnosis. In patients splenomegaly, hepatomegaly, and jaundice. Laboratory with pulmonary disease, the BAL and serum galactomannan abnormalities reflect the presence of hemolytic anemia; assay have excellent sensitivity and speciflcity (both >80'/,) in thrombocytopenia and elevated aminotransferase and patients with hematologic malignancies or following hemato- alkaline phosphatase levels are also common. Occasion poietic stem cell transplantation. ally, the diagnosis is made incidentally in asymptom- Candida crlbicons is a common cause of candidemia atic patients when intraerythrocytic rings are seen on a (Option B), but it rarely produces infections in the respira- peripheral blood smear. tory tract. Adclitionally, because most patients with acute Cytomegalovirus can be transmitted through trans- leukemia undergoing initial-induction chemotherapy are fusion and causes a mononucleosis like illness with receiving fluconazole prophylaxis, invasive candidiasis fever, absolute lymphocytosis, and thrombocytope- does not occur unless it is with a resistant species such as nia but does not commonly cause hemolytic anemia Candtda glabrata or Candida auris. (Option B). Cryptococc'us neoformons (Option C) cclmmonly causes Ehrlichiosis is a tick-borne infection that can rarely inf'ections in immunocompromised persons; however, this be transmitted through transfusion (Option C). Laboratory patient has no evidence of central nervous system involve abnormalities with ehrlichiosis include leukopenia, throm- ment, where this illness most commonly manifbsts. However, bocytopenia, and elevated aminotransferase levels ; hemoly- cryptococcal pneumonia can occur in immunocompromised sis is not seen with this infection. patients and typically presents with infiltrates, lymphade Leptospirosis can cause fever and cholestasis, but the nopathy, and mass lesions. Invasive aspergillosis is a more patient has no compatible history of travel, environmen common cause of'pneumonia in immunocompromised hosts, tal exposure, or animal exposure to support this diagnosis and the positive galactomannan assay supprtrts this diagnosis. (Option D). H istoplas ma capsulatu m (Option D) gene ral ly produces Parvovirus B-19 causes fever and anemia, but the asynrptomatic pulmonary inf'ection, but it is not typically anemia results from red cell aplasia rather than hemolysis associated with cavitary lung lesions in int'ected persons and (Option E). is not assc.rciated with a positive galactomannan assay. IEY PO I1{T I(EY POIilTS . Transfusion-transmitted babesiosis should be consid- o Profound and prolonged neutropenia, especially in ered in the differential diagnosis of posttransfusion association with hematopoietic stem cell transplanta- fever and hemolysis. tion or chemotherapy, is a risk factor for invasive aspergillosis. Bibliography o In patients with invasive pulmonary aspergillosis, bron- Westblade LE, Simon MS, Mathison BA, et al. Babesia microti: from mice to ticks to an increasing number of highly susceptible humans. J Clin choalveolar lavage and serum galactomannan assay Microbiol. 2Ol7;55:2903-2912. [PMID: Ze%lTql doi:10.1128/JCM. have excellent diagnostic sensitivity and specificity. 00504 17

IEY PO I1{T I(EY POIilTS . Transfusion-transmitted babesiosis should be consid- o Profound and prolonged neutropenia, especially in ered in the differential diagnosis of posttransfusion association with hematopoietic stem cell transplanta- fever and hemolysis. tion or chemotherapy, is a risk factor for invasive aspergillosis. Bibliography o In patients with invasive pulmonary aspergillosis, bron- Westblade LE, Simon MS, Mathison BA, et al. Babesia microti: from mice to ticks to an increasing number of highly susceptible humans. J Clin choalveolar lavage and serum galactomannan assay Microbiol. 2Ol7;55:2903-2912. [PMID: Ze%lTql doi:10.1128/JCM. have excellent diagnostic sensitivity and specificity. 00504 17 181

Answers and Critiques Bibliography f,EY POITT Wasylyshyn A, Linder KA, Castillo CG, et al. Breakthrough in'rasive fungal o Empiric management of suspected health care- infections in patients with acute myeloid leukemia. Mycopathologia. 2020;185:299-306. IPMID: 31939052] doi:10.1007/s11046-019 associated ventriculitis or meningitis should include 00418-B vancomycin and a B-lactam with antipseudomonal activity (such as cefepime or meropenem) and device removal, if present. Item 85 Answer: C tr Educational Objective: Treat health care-associated Bibliography ventriculitis or meningitis. Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventricu- The nrost appropriate managelnent in this patiellt is litis and meningitis. Clin Infect Dis. 2017;64:e34-e65. [ptr,'ttO' 28203777) doi: 10. 1093 /cid/ciwB6l intravenous vancornycin and cef'epinte plus shultt removal (Option C) and placet.nent of'a tentporary exter t-r nal ventricular clrain. Health c:lre associated ventrictt Item 86 Answer: B (D = litis or menirrgitis (tlCAVM) can represent l cliagnostic Ed ucationa I Objective: Diagnose acute retroviral -q, UI and treatmer-rt challenge. lt typically occlrrs after head syndrome in a patient at risk for HIV infection. ) CL trauma or a neurosurgical procedure (e.g.. craniotonry, lur-nbar puncture) <-rr secor-rclary to device inf'ectior-r (e.g., The most appropriate next step in management would be n *- cerebrospinal fluid [CSF] shunts or drair-rs, intratl-recal punlps, deep brain stimulator). Sroplt,tll<tcoc'cus spe to perform HIV-1 RNA nucleic acid ampliflcation testing (UAAT) (Option B). The patient's symptoms are worrisome lt .- F D cies and enteric grirnl-llegittive bacteria are the most for acute retroviral syndrome, and acute HIV infection must UI be ruled out before proceeding with pre exposure prophy conllron causes. but up to 50')1, of patients can have negative cultures because rlorc than 50'/,, receive anti laxis (PrEP). The HIV p24 antigen and HIV-1/HIV-2 anti- biotic therapy befbre CSF studies are perftrrmed. Wors body detection tests have signiflcantly reduced the window ening mental statLls, headaches. f'ever. or stif'f'neck in ir period (time from exposure to positive screening test) from patient who recently underwent surgery or has a shunt previous tests. However, in the setting of acute retroviral shoulcl raise suspicion fbr IICAVM. An elevated CSF lac syndrome, screening tests could be negative if performed tate level greater than 0.44 n-rg'dL (4 r-r-rr-nol,L). an ele too early in the course of infection. With his symptoms of vated CSF procalcitonin level. or botl-r. n-ray be useful fitr fatigue, body aches, and sore throat and flndings of lym- diagnosis when cultures are negirtive. l:ntpiric therapy phadenopathy, which could be related to acute retrovi- should include intravenous vilncofilycin ancl a B lactant ral syndrome, the most appropriate testing following the n,ith antipseuclomonal activity (such as cet'epime or negative HIV antigen/antibody combination assay would be meropenern) ar-rd device renrovirl. if' present. If possi HIV 1 RNA NAAT. ble. inf'ected CSF' shunts and other devices should be If the HIV 1 RNA is positive, further evaluation will removed because sofile pathogelrs fbnn biofilrns on pros be needed, including testing for baseline CD4 cell count thetic material and are resistant tr-r antinticrobial treat and other co-infections (Option A). However, assessing this rxent. If a causative pathogen is identillecl. the regirler-r patient's CD4 cell count without conflrming the diagnosis should be narror,t ed :rccordingly. of HIV infection does not provide beneflt and should be lntravenous ampicillin irnd ceftriaxone (Option A) are avoided. an appropriate enrpiric antibiotic combination fbr patients Considering he is in a high risk group for HIV acqui- older than 50 years or rn,ith altered cell rnediated immu sition, this patient would certainly beneflt from HIV nity such as systernic lupus ervthematosus. Antpicillin lvill pre-exposure prophylaxis with tenofovir-emtricitabine provide adequate coverage tbr Listericl nrorrocytogenes (Option C). However, acute HIV infection must be ruled in these patients, but it is inadequate fbr a patient with out flrst. If an alternate explanation is found, he can start HCAVM. HIV pre-exposure prophylaxis, with follow-up HIV test- Intravenous vancorlycin and ceftazidirne. cef'epime, or ing (fourth generation HIV-1/2 antigen/antibody testing meropenem are acceptable reginrens fbr the crnpiric treat at least every 3 months) as recommended by the CDC nrent of'HCAVM (Option B), but therapy should also include guidelines. removal of the inf'ected shunt and placement of a temporary Starting antiretroviral therapy with tenofovir- external drair-r. emtricitabine plus dolutegravir without testing HIV 1 RNA No randomized controlled trials dernonstrate eitl-rer to conflrm acute HIV infection exposes the patient to unnec- tl-re saf'ety or efficacy of intraventricular antibiotics to treat essary toxicity from these antiretroviral agents (Option D). HCAVM (Option D), and no rntibiotics are approved fbr Likewise, this combination of antiretroviral agents cannot this indication. lntraventricular adrninistration of antibi be administered as a postexposure prophylaxis regimen otics is potentially to.xic but can be used in patients with because his last potential exposure was 2 weeks ago; post multidrug-resistant rlrganisnts that are not responding to exposure prophylaxis is not recommended if more than intravenous therapy. 72 hours have passed.

Bibliography f,EY POITT Wasylyshyn A, Linder KA, Castillo CG, et al. Breakthrough in'rasive fungal o Empiric management of suspected health care- infections in patients with acute myeloid leukemia. Mycopathologia. 2020;185:299-306. IPMID: 31939052] doi:10.1007/s11046-019 associated ventriculitis or meningitis should include 00418-B vancomycin and a B-lactam with antipseudomonal activity (such as cefepime or meropenem) and device removal, if present. Item 85 Answer: C tr Educational Objective: Treat health care-associated Bibliography ventriculitis or meningitis. Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventricu- The nrost appropriate managelnent in this patiellt is litis and meningitis. Clin Infect Dis. 2017;64:e34-e65. [ptr,'ttO' 28203777) doi: 10. 1093 /cid/ciwB6l intravenous vancornycin and cef'epinte plus shultt removal (Option C) and placet.nent of'a tentporary exter t-r nal ventricular clrain. Health c:lre associated ventrictt Item 86 Answer: B (D = litis or menirrgitis (tlCAVM) can represent l cliagnostic Ed ucationa I Objective: Diagnose acute retroviral -q, UI and treatmer-rt challenge. lt typically occlrrs after head syndrome in a patient at risk for HIV infection. ) CL trauma or a neurosurgical procedure (e.g.. craniotonry, lur-nbar puncture) <-rr secor-rclary to device inf'ectior-r (e.g., The most appropriate next step in management would be n *- cerebrospinal fluid [CSF] shunts or drair-rs, intratl-recal punlps, deep brain stimulator). Sroplt,tll<tcoc'cus spe to perform HIV-1 RNA nucleic acid ampliflcation testing (UAAT) (Option B). The patient's symptoms are worrisome lt .- F D cies and enteric grirnl-llegittive bacteria are the most for acute retroviral syndrome, and acute HIV infection must UI be ruled out before proceeding with pre exposure prophy conllron causes. but up to 50')1, of patients can have negative cultures because rlorc than 50'/,, receive anti laxis (PrEP). The HIV p24 antigen and HIV-1/HIV-2 anti- biotic therapy befbre CSF studies are perftrrmed. Wors body detection tests have signiflcantly reduced the window ening mental statLls, headaches. f'ever. or stif'f'neck in ir period (time from exposure to positive screening test) from patient who recently underwent surgery or has a shunt previous tests. However, in the setting of acute retroviral shoulcl raise suspicion fbr IICAVM. An elevated CSF lac syndrome, screening tests could be negative if performed tate level greater than 0.44 n-rg'dL (4 r-r-rr-nol,L). an ele too early in the course of infection. With his symptoms of vated CSF procalcitonin level. or botl-r. n-ray be useful fitr fatigue, body aches, and sore throat and flndings of lym- diagnosis when cultures are negirtive. l:ntpiric therapy phadenopathy, which could be related to acute retrovi- should include intravenous vilncofilycin ancl a B lactant ral syndrome, the most appropriate testing following the n,ith antipseuclomonal activity (such as cet'epime or negative HIV antigen/antibody combination assay would be meropenern) ar-rd device renrovirl. if' present. If possi HIV 1 RNA NAAT. ble. inf'ected CSF' shunts and other devices should be If the HIV 1 RNA is positive, further evaluation will removed because sofile pathogelrs fbnn biofilrns on pros be needed, including testing for baseline CD4 cell count thetic material and are resistant tr-r antinticrobial treat and other co-infections (Option A). However, assessing this rxent. If a causative pathogen is identillecl. the regirler-r patient's CD4 cell count without conflrming the diagnosis should be narror,t ed :rccordingly. of HIV infection does not provide beneflt and should be lntravenous ampicillin irnd ceftriaxone (Option A) are avoided. an appropriate enrpiric antibiotic combination fbr patients Considering he is in a high risk group for HIV acqui- older than 50 years or rn,ith altered cell rnediated immu sition, this patient would certainly beneflt from HIV nity such as systernic lupus ervthematosus. Antpicillin lvill pre-exposure prophylaxis with tenofovir-emtricitabine provide adequate coverage tbr Listericl nrorrocytogenes (Option C). However, acute HIV infection must be ruled in these patients, but it is inadequate fbr a patient with out flrst. If an alternate explanation is found, he can start HCAVM. HIV pre-exposure prophylaxis, with follow-up HIV test- Intravenous vancorlycin and ceftazidirne. cef'epime, or ing (fourth generation HIV-1/2 antigen/antibody testing meropenem are acceptable reginrens fbr the crnpiric treat at least every 3 months) as recommended by the CDC nrent of'HCAVM (Option B), but therapy should also include guidelines. removal of the inf'ected shunt and placement of a temporary Starting antiretroviral therapy with tenofovir- external drair-r. emtricitabine plus dolutegravir without testing HIV 1 RNA No randomized controlled trials dernonstrate eitl-rer to conflrm acute HIV infection exposes the patient to unnec- tl-re saf'ety or efficacy of intraventricular antibiotics to treat essary toxicity from these antiretroviral agents (Option D). HCAVM (Option D), and no rntibiotics are approved fbr Likewise, this combination of antiretroviral agents cannot this indication. lntraventricular adrninistration of antibi be administered as a postexposure prophylaxis regimen otics is potentially to.xic but can be used in patients with because his last potential exposure was 2 weeks ago; post multidrug-resistant rlrganisnts that are not responding to exposure prophylaxis is not recommended if more than intravenous therapy. 72 hours have passed. 182

Answers and Critiques KEY POIt{TS Bibliography o In patients presenting with symptoms worrisome Li HK, Rombach I, Zambellas R, et al; OVIVA Trial Collaborators. Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med. 2019; for acute HIV infection but with negative HIV p24 380:425 436. IPMID: SO0SSet S] doi:10.1056 / NElMoal7lO926 antigen and HIV-1lHlV-2 antibody detection tests, HIV 1 RNA nucleic acid amplification testing should be performed to confirm the diagnosis. Item 88 Answer: C . HIV infection must be ruled out before starting Ed u cati o n a I O biective : Treat Cryptosporidium- associated diarrhea. pre-exposure prophylaxis. This patient should receive nitazoxanide (Option C), which Bibliography is approved for the treatment of two protozoal gastrointesti- Hurt CB, Nelson JAE, Hightow Weidman LB, et al. Selecting an nal pathogens, Cryptosporidium and Giardio. Symptoms of HIV test: A narrative review for clinicians and researchers. Sex cryptosporidiosis usually last less than 2 weeks before spon- t/l Transm Dis. 2017;44:739-746. [PI,UO, 29I4OB9OI doi:10.1097/OLQ. (u taneously resolving in immunocompetent hosts. Immuno- J 000000000000071 9 ET compromised patients, in particular patients with AIDS, can .I F .I

KEY POIt{TS Bibliography o In patients presenting with symptoms worrisome Li HK, Rombach I, Zambellas R, et al; OVIVA Trial Collaborators. Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med. 2019; for acute HIV infection but with negative HIV p24 380:425 436. IPMID: SO0SSet S] doi:10.1056 / NElMoal7lO926 antigen and HIV-1lHlV-2 antibody detection tests, HIV 1 RNA nucleic acid amplification testing should be performed to confirm the diagnosis. Item 88 Answer: C . HIV infection must be ruled out before starting Ed u cati o n a I O biective : Treat Cryptosporidium- associated diarrhea. pre-exposure prophylaxis. This patient should receive nitazoxanide (Option C), which Bibliography is approved for the treatment of two protozoal gastrointesti- Hurt CB, Nelson JAE, Hightow Weidman LB, et al. Selecting an nal pathogens, Cryptosporidium and Giardio. Symptoms of HIV test: A narrative review for clinicians and researchers. Sex cryptosporidiosis usually last less than 2 weeks before spon- t/l Transm Dis. 2017;44:739-746. [PI,UO, 29I4OB9OI doi:10.1097/OLQ. (u taneously resolving in immunocompetent hosts. Immuno- J 000000000000071 9 ET compromised patients, in particular patients with AIDS, can .I F .I develop serious and prolonged infection. Despite supportive rJ L

KEY POIt{TS Bibliography o In patients presenting with symptoms worrisome Li HK, Rombach I, Zambellas R, et al; OVIVA Trial Collaborators. Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med. 2019; for acute HIV infection but with negative HIV p24 380:425 436. IPMID: SO0SSet S] doi:10.1056 / NElMoal7lO926 antigen and HIV-1lHlV-2 antibody detection tests, HIV 1 RNA nucleic acid amplification testing should be performed to confirm the diagnosis. Item 88 Answer: C . HIV infection must be ruled out before starting Ed u cati o n a I O biective : Treat Cryptosporidium- associated diarrhea. pre-exposure prophylaxis. This patient should receive nitazoxanide (Option C), which Bibliography is approved for the treatment of two protozoal gastrointesti- Hurt CB, Nelson JAE, Hightow Weidman LB, et al. Selecting an nal pathogens, Cryptosporidium and Giardio. Symptoms of HIV test: A narrative review for clinicians and researchers. Sex cryptosporidiosis usually last less than 2 weeks before spon- t/l Transm Dis. 2017;44:739-746. [PI,UO, 29I4OB9OI doi:10.1097/OLQ. (u taneously resolving in immunocompetent hosts. Immuno- J 000000000000071 9 ET compromised patients, in particular patients with AIDS, can .I F .I develop serious and prolonged infection. Despite supportive rJ L care, including an antimotility agent and initiation of antiret- !, Item 87 Answer: A roviral therapy (ART), this patient with HIV infection has per- E ,tr Educational Objective: Treat methicillin-susceptible sistent and frequent diarrhea. In general, immune reconstitu- UI fr Staphylococcus aureus osteomyelitis with oral tion with combination ART is the cornerstone of management o antibiotics. for patients with HIV associated cryptosporidiosis. However, UI = E symptom resolution, which Szpically occurs at signiflcantly Oral doxycycline is an appropriate treatment option for higher CD4 cell counts (>100/pL), may be delayed, so patients this patient with osteomyelitis caused by methicillin- with persistent and debilitating diarrhea can be given nitazox- susceptible Staphylococcus aLtreus (MSSA) (Option A). anide. If uncontrolled, particularly in persons with advanced The much anticipated OVIVA study published in January HIV disease, cryptosporidiosis can cause profound wasting, 2019 showed that oral antibiotics with high bioavail- with associated malaise, crampy abdominal pain, nausea, ability were noninferior to intravenous antibiotics for vomiting, and fever. Patients treated for cryptosporidial diar the management of osteomyelitis. Although data from rhea should avoid swimming in public pools for 2 weeks after randomized controlled trials is scarce. a treatment dura- the diarrhea has resolved. This parasite is tolerant to chlorine tion of 6 weeks has been generally recommended for and can persist for days in a chlorinated pool. Swallowing osteomyelitis in adults. Longer courses of therapy may be contaminated water can result in infection. Cryptosporidium necessary in infections with significant residual necrotic has become the leading cause of swimming pool-related out- bone, in the setting of orthopedic hardware when the breaks of diarrheal illness in otherwise healthy persons. hardware cannot be removed, or when oral antibiotics Atovaquone (Option A) has activi[z against some pro- are used. tozoans, including Babesia, Toxoplasmo, and Plasmodium, If parenteral therapy is chosen, the most narrow- but not Cryptosporidium. spectrum agent to which the isolate is susceptible should be Ciprofloxacin (Option B) is active against numerous used. Ceftaroline (Option B) has been shown to be successful bacterial gastrointestinal pathogens, including Campylo in osteomyelitis management and has activity against MSSA bacter, Salmonella, Shigella, Vibrio, Yersinia, and poten but is also active against methicillin-resistant S. oureus (MRSA) and gram negative pathogens. This agent would tially the protozoan Cystoisosporo, but it is not effective against Cryptosporidium. be unnecessarily broad for treating an infection caused by Metronidazole (Option D) has activity against some MSSA. protozoans, includi n g Entamoeb a, Trichomonas, and Gio r Piperacillin-tazobactam (Option C) has activity dio, but not Cryptosporidium. against MSSA but also has broad-spectrum activity against gram negatives and anaerobes, so it would be unnecessarily t(EY POt l{TS broad for a monomicrobial MSSA infection. . Cry,ptosporidial infection is a leading cause of swimming Parenteral vancomycin (Option D) is reserved for treat- pool related diarrheal illness. ment of MRSA infections or in those patients with MSSA and o Nitazoxanide is the treatment for persistent and debil- severe allergies to effective agents. itating cryptosporidial diarrhea in patients with HIV I(EY PO I T{T infection awaiting immune reconstitution. . Oral antibiotics (such as doxycycline) with high bio- Bibliography availability have been shown to be noninferior to Shane AL, Mody RK, Crump lA, et al. 2017 Inlectious Diseases Society of intravenous antibiotics for the management of America clinical practice guidelines for the diagnosis and management osteomyelitis. of infectious diarrhea. Clin Infect Dis.2017;65:e45 e80. [PMID: ZSOSSISZ) doi :1 0.1093 /cid/cix669

care, including an antimotility agent and initiation of antiret- !, Item 87 Answer: A roviral therapy (ART), this patient with HIV infection has per- E ,tr Educational Objective: Treat methicillin-susceptible sistent and frequent diarrhea. In general, immune reconstitu- UI fr Staphylococcus aureus osteomyelitis with oral tion with combination ART is the cornerstone of management o antibiotics. for patients with HIV associated cryptosporidiosis. However, UI = E symptom resolution, which Szpically occurs at signiflcantly Oral doxycycline is an appropriate treatment option for higher CD4 cell counts (>100/pL), may be delayed, so patients this patient with osteomyelitis caused by methicillin- with persistent and debilitating diarrhea can be given nitazox- susceptible Staphylococcus aLtreus (MSSA) (Option A). anide. If uncontrolled, particularly in persons with advanced The much anticipated OVIVA study published in January HIV disease, cryptosporidiosis can cause profound wasting, 2019 showed that oral antibiotics with high bioavail- with associated malaise, crampy abdominal pain, nausea, ability were noninferior to intravenous antibiotics for vomiting, and fever. Patients treated for cryptosporidial diar the management of osteomyelitis. Although data from rhea should avoid swimming in public pools for 2 weeks after randomized controlled trials is scarce. a treatment dura- the diarrhea has resolved. This parasite is tolerant to chlorine tion of 6 weeks has been generally recommended for and can persist for days in a chlorinated pool. Swallowing osteomyelitis in adults. Longer courses of therapy may be contaminated water can result in infection. Cryptosporidium necessary in infections with significant residual necrotic has become the leading cause of swimming pool-related out- bone, in the setting of orthopedic hardware when the breaks of diarrheal illness in otherwise healthy persons. hardware cannot be removed, or when oral antibiotics Atovaquone (Option A) has activi[z against some pro- are used. tozoans, including Babesia, Toxoplasmo, and Plasmodium, If parenteral therapy is chosen, the most narrow- but not Cryptosporidium. spectrum agent to which the isolate is susceptible should be Ciprofloxacin (Option B) is active against numerous used. Ceftaroline (Option B) has been shown to be successful bacterial gastrointestinal pathogens, including Campylo in osteomyelitis management and has activity against MSSA bacter, Salmonella, Shigella, Vibrio, Yersinia, and poten but is also active against methicillin-resistant S. oureus (MRSA) and gram negative pathogens. This agent would tially the protozoan Cystoisosporo, but it is not effective against Cryptosporidium. be unnecessarily broad for treating an infection caused by Metronidazole (Option D) has activity against some MSSA. protozoans, includi n g Entamoeb a, Trichomonas, and Gio r Piperacillin-tazobactam (Option C) has activity dio, but not Cryptosporidium. against MSSA but also has broad-spectrum activity against gram negatives and anaerobes, so it would be unnecessarily t(EY POt l{TS broad for a monomicrobial MSSA infection. . Cry,ptosporidial infection is a leading cause of swimming Parenteral vancomycin (Option D) is reserved for treat- pool related diarrheal illness. ment of MRSA infections or in those patients with MSSA and o Nitazoxanide is the treatment for persistent and debil- severe allergies to effective agents. itating cryptosporidial diarrhea in patients with HIV I(EY PO I T{T infection awaiting immune reconstitution. . Oral antibiotics (such as doxycycline) with high bio- Bibliography availability have been shown to be noninferior to Shane AL, Mody RK, Crump lA, et al. 2017 Inlectious Diseases Society of intravenous antibiotics for the management of America clinical practice guidelines for the diagnosis and management osteomyelitis. of infectious diarrhea. Clin Infect Dis.2017;65:e45 e80. [PMID: ZSOSSISZ) doi :1 0.1093 /cid/cix669 183

Answers and Critiques Item 89 tr Answer: B Ed ucatio na I Objective : Monitor vancomycin therapy. Bibliography Rybak MJ. Le J. Lodise TB et al. Therapeutic monitoring of vancomycin for serious methicillin resistant Staphylococcus oureus infections: A revised consensus guideline and review by the American Society of Area under tl-re curve (AIJC) vancom),,cin-guided dos Health-system Pharmacists, the Infectious Diseases Society of America, ing (Option B) is now recommended when treating se\ere the Pediatric Infectious Diseases Sociery and the Society of Infectious Diseases Pharmacists. Clin Infect Dis. 2020;71:1361-1364. [PMIO, methicillin-resistant Staphylococcus oureus (MRSA) infec- szosasoel doi:10.1093/cid/ciaa303 tions. particularly complicated bloodstream infections. Dos ing is done in consultation with the pharmacy. When treating MRSA endocarditis, the AUC to minimum inhibitory con- Item 90 Answer: D centration (MIC) ratio (AUC/MIC) should be used for dosing vancomycin. The target AUC/MIC is 400 to 600 mg*hour,'L Ed ucationa I Objective: Diagnose mucormycosis.

Item 89 tr Answer: B Ed ucatio na I Objective : Monitor vancomycin therapy. Bibliography Rybak MJ. Le J. Lodise TB et al. Therapeutic monitoring of vancomycin for serious methicillin resistant Staphylococcus oureus infections: A revised consensus guideline and review by the American Society of Area under tl-re curve (AIJC) vancom),,cin-guided dos Health-system Pharmacists, the Infectious Diseases Society of America, ing (Option B) is now recommended when treating se\ere the Pediatric Infectious Diseases Sociery and the Society of Infectious Diseases Pharmacists. Clin Infect Dis. 2020;71:1361-1364. [PMIO, methicillin-resistant Staphylococcus oureus (MRSA) infec- szosasoel doi:10.1093/cid/ciaa303 tions. particularly complicated bloodstream infections. Dos ing is done in consultation with the pharmacy. When treating MRSA endocarditis, the AUC to minimum inhibitory con- Item 90 Answer: D centration (MIC) ratio (AUC/MIC) should be used for dosing vancomycin. The target AUC/MIC is 400 to 600 mg*hour,'L Ed ucationa I Objective: Diagnose mucormycosis. to maximize clinical efficacy and minimize nephrotoxicity. The most likely diagnosis is mucormycosis (Option D) D For empiric therapy, the AUC/MIC calculation assumes the caused by genera in the order Mucorales. Mucormycosis J UI vancomycin MIC to be 1 pg/ml or less. The appropriate AUC/ is the third most frequent cause of invasive fungal infec- MIC ratio should be achieved early, preferably within the flrst tions in immunocompromised persons but is rarely seen in = .D rt 24 to 48 hours of treatment. AUC-guided dosing requires UI immunocompetent persons. Particularly at risk are patients o, collecting several vancomycin concentrations. the timing of J with neutropenia, diabetes mellitus, and acidosis. The most IL which should be determined by the pharmacy. Vancomy- common mucormycetes are Rhizopus arrhizus and Mucor r,| -eJt cin is the preferred antimicrobial agent for this patient with MRSA tricuspid valve endocarditis. Blood cultures should be species. Infection is acute and rapidly fatal, even with early tt -a diagnosis and treatment. Major blood vessels are invaded, E repeated until sustained clearance of bacteremia is demon- with ensuing ischemia, necrosis, and infarction of adja- (D IA strated. Monitoring kidney function during treatment is also cent tissues. Mucormycosis has flve major clinical forms: important. (1) rhinocerebral; (2) pulmonary; (g) abdominal, pelvic, Combination antibiotic treatment for MRSA endocar- gastric, gastrointestinal; (4) primary cutaneous; and (5) ditis (vancomycin. gentamicin, and rifampir-r) (Option A) disseminated. The presence of oral necrotic lesions strongly is used in cases of prosthetic valve endocarditis. Combi- indicates an invasive mucor infection in this patient. This nation treatment has no role in MRSA native valve endo- patient has left eye proptosis, with accompanying ptosis carditis or bacteremia without endocarditis and should of the upper lid, and generalized palpebral swelling and be avoided. erythema, and left facial drooping. Signs of orbital infection Daptomycin (Option C) should be considered for the include periorbital edema, proptosis, and blindness. Spread treatment of MRSA infections when the isolate's vanco from the sphenoid sinuses to the adjacent cavernous sinus mycin MIC is greater than 2 pg/ml or rnhen the vancomy can result in cranial nerve palsies (cranial nerve VII in this cin MIC is close to 2 pg/ml and clinical response is poor case), sinus thrombosis, and carotid artery involvement. (e.g., persistent bacteremia beyond the expected period for Deflnitive diagnosis frequently requires a biopsy with histo- endocarditis). The isolate should first be tested to ensure it is pathologic examination, which is the most sensitive form of susceptible to daptomycin. diagnosis. Treatment requires reversal of any predisposing Telavancin (Option D) is a lipoglycopeptide derivative condition, extensive surgical removal of affected tissue, and of vancomycin and can be administered with once-daily early antifungal therapy. Initial treatment is high-dose lipo- dosing. [t appears to be as effective as vancomycin in treat somal amphotericin B, with later de-escalation to posacon- ing MRSA inf'ections but is associated with more adverse azole or isavuconazonium sulfate. effects, including kidney injury. This patient has no indi- Invasive sinusitis with Aspergillus species (Option A) cations to switch from vancomycin to telavancin. a more typically occurs in patients with speciflc risk factors such toxic drug. as neutropenia or chemotherapy administration. Deflnitive diagnosis could be achieved by either fungal culture or poly XEY POITTS merase chain reaction. o When treating methici llin-resistant Staphylococcus Signs and symptoms of focalCandidainfection (Option aureus bacteremia with vancomycin, area under the B) depend on the site involved (abscess or peritonitis in the curve guided dosing and monitoring should be used peritoneum, empyema in the pleural cavity, or pyelonephri- to achieve clinical efficacy and decrease risk of tis in the kidneys). Other forms of invasive infection include nephrotoxicity. meningitis, osteomyelitis, septic arthritis, and endocarditis. o Daptomycin should be considered for the treatment of Any Candido infections involving the sinuses and associated mcthicillin resistant Staphylococcus aureus when skin and mucous structures are extremely rare. the isolate's vancomycin minimum inhibitory con- Although uncontrolled diabetes mellitus should be centration (MIC) is greater than 2 pg/ml or when the considered a risk factor for cryptococcosis, infections with vancomycin MIC is close to 2 pg/ml and clinical Cryptococcus (Option C) rarely produce sinusitis. More commonly, cryptococcal infections involve the central ner- response is poor. vous system.

to maximize clinical efficacy and minimize nephrotoxicity. The most likely diagnosis is mucormycosis (Option D) D For empiric therapy, the AUC/MIC calculation assumes the caused by genera in the order Mucorales. Mucormycosis J UI vancomycin MIC to be 1 pg/ml or less. The appropriate AUC/ is the third most frequent cause of invasive fungal infec- MIC ratio should be achieved early, preferably within the flrst tions in immunocompromised persons but is rarely seen in = .D rt 24 to 48 hours of treatment. AUC-guided dosing requires UI immunocompetent persons. Particularly at risk are patients o, collecting several vancomycin concentrations. the timing of J with neutropenia, diabetes mellitus, and acidosis. The most IL which should be determined by the pharmacy. Vancomy- common mucormycetes are Rhizopus arrhizus and Mucor r,| -eJt cin is the preferred antimicrobial agent for this patient with MRSA tricuspid valve endocarditis. Blood cultures should be species. Infection is acute and rapidly fatal, even with early tt -a diagnosis and treatment. Major blood vessels are invaded, E repeated until sustained clearance of bacteremia is demon- with ensuing ischemia, necrosis, and infarction of adja- (D IA strated. Monitoring kidney function during treatment is also cent tissues. Mucormycosis has flve major clinical forms: important. (1) rhinocerebral; (2) pulmonary; (g) abdominal, pelvic, Combination antibiotic treatment for MRSA endocar- gastric, gastrointestinal; (4) primary cutaneous; and (5) ditis (vancomycin. gentamicin, and rifampir-r) (Option A) disseminated. The presence of oral necrotic lesions strongly is used in cases of prosthetic valve endocarditis. Combi- indicates an invasive mucor infection in this patient. This nation treatment has no role in MRSA native valve endo- patient has left eye proptosis, with accompanying ptosis carditis or bacteremia without endocarditis and should of the upper lid, and generalized palpebral swelling and be avoided. erythema, and left facial drooping. Signs of orbital infection Daptomycin (Option C) should be considered for the include periorbital edema, proptosis, and blindness. Spread treatment of MRSA infections when the isolate's vanco from the sphenoid sinuses to the adjacent cavernous sinus mycin MIC is greater than 2 pg/ml or rnhen the vancomy can result in cranial nerve palsies (cranial nerve VII in this cin MIC is close to 2 pg/ml and clinical response is poor case), sinus thrombosis, and carotid artery involvement. (e.g., persistent bacteremia beyond the expected period for Deflnitive diagnosis frequently requires a biopsy with histo- endocarditis). The isolate should first be tested to ensure it is pathologic examination, which is the most sensitive form of susceptible to daptomycin. diagnosis. Treatment requires reversal of any predisposing Telavancin (Option D) is a lipoglycopeptide derivative condition, extensive surgical removal of affected tissue, and of vancomycin and can be administered with once-daily early antifungal therapy. Initial treatment is high-dose lipo- dosing. [t appears to be as effective as vancomycin in treat somal amphotericin B, with later de-escalation to posacon- ing MRSA inf'ections but is associated with more adverse azole or isavuconazonium sulfate. effects, including kidney injury. This patient has no indi- Invasive sinusitis with Aspergillus species (Option A) cations to switch from vancomycin to telavancin. a more typically occurs in patients with speciflc risk factors such toxic drug. as neutropenia or chemotherapy administration. Deflnitive diagnosis could be achieved by either fungal culture or poly XEY POITTS merase chain reaction. o When treating methici llin-resistant Staphylococcus Signs and symptoms of focalCandidainfection (Option aureus bacteremia with vancomycin, area under the B) depend on the site involved (abscess or peritonitis in the curve guided dosing and monitoring should be used peritoneum, empyema in the pleural cavity, or pyelonephri- to achieve clinical efficacy and decrease risk of tis in the kidneys). Other forms of invasive infection include nephrotoxicity. meningitis, osteomyelitis, septic arthritis, and endocarditis. o Daptomycin should be considered for the treatment of Any Candido infections involving the sinuses and associated mcthicillin resistant Staphylococcus aureus when skin and mucous structures are extremely rare. the isolate's vancomycin minimum inhibitory con- Although uncontrolled diabetes mellitus should be centration (MIC) is greater than 2 pg/ml or when the considered a risk factor for cryptococcosis, infections with vancomycin MIC is close to 2 pg/ml and clinical Cryptococcus (Option C) rarely produce sinusitis. More commonly, cryptococcal infections involve the central ner- response is poor. vous system. 184

Answers and Critiques r(EY P0l1{TS KEY POI l{T o Uncontrolled diabetes mellitus is a significant risk . Bone biopsy should be performed before initiating factor for mucormycosis. treatment for osteomyelitis because microbiologic o Mucormycosis should be strongly suspected in immu- culture results will guide antibiotic therapy selection. nocompromised persons presenting with an oral or rhinocerebral necrotic lesion. Bibliography Schmitt SK. Osteomyelitis. lnfect Dis Clin North Am. 2017;31:325-338 IPM ID : Z9.4SSO q ql doi:10. 101 6 /j. idc. 2017. ol. 010 Bibliography Cornely OA, Alastruey Izquierdo A, Arenz D, et al; Mucormycosis ECMM MSG Global Guideline Writing Group. Global guideline for the diagno- sis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. Item 92 Answer: Educational Objective: Treat pelvic inflammatory E tr UI (l, 2Ol9;19:e405-e421. IPMID: 31699664] doi:10.1076151473 3099(19) disease in a patient requiring hospitalization. 3031 2-3 - d ET Clindarnycin and gentamicin are appropriate antibiotic .I H a- b management for women with pelvic inflammatory disease rJ Item 91 Answer: A (PID) who require hospitalization (Option E). Signs of severe ?t ? systemic toxicity or an inabilify to tolerate oral antibiotics, r-! Educational Objective: Diagnose the microbial cause of ra pregnancy, tubo-ovarian abscess, inability to exclude a sur- L osteomyelitis with a bone biopsy. €, gical emergency, or failed outpatier-rt antibiotic therapy are vt = The patient should undergo a bone biopsy to establish the indications ftlr hospitalization and parenteral therapy in ?

r(EY P0l1{TS KEY POI l{T o Uncontrolled diabetes mellitus is a significant risk . Bone biopsy should be performed before initiating factor for mucormycosis. treatment for osteomyelitis because microbiologic o Mucormycosis should be strongly suspected in immu- culture results will guide antibiotic therapy selection. nocompromised persons presenting with an oral or rhinocerebral necrotic lesion. Bibliography Schmitt SK. Osteomyelitis. lnfect Dis Clin North Am. 2017;31:325-338 IPM ID : Z9.4SSO q ql doi:10. 101 6 /j. idc. 2017. ol. 010 Bibliography Cornely OA, Alastruey Izquierdo A, Arenz D, et al; Mucormycosis ECMM MSG Global Guideline Writing Group. Global guideline for the diagno- sis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. Item 92 Answer: Educational Objective: Treat pelvic inflammatory E tr UI (l, 2Ol9;19:e405-e421. IPMID: 31699664] doi:10.1076151473 3099(19) disease in a patient requiring hospitalization. 3031 2-3 - d ET Clindarnycin and gentamicin are appropriate antibiotic .I H a- b management for women with pelvic inflammatory disease rJ Item 91 Answer: A (PID) who require hospitalization (Option E). Signs of severe ?t ? systemic toxicity or an inabilify to tolerate oral antibiotics, r-! Educational Objective: Diagnose the microbial cause of ra pregnancy, tubo-ovarian abscess, inability to exclude a sur- L osteomyelitis with a bone biopsy. €, gical emergency, or failed outpatier-rt antibiotic therapy are vt = The patient should undergo a bone biopsy to establish the indications ftlr hospitalization and parenteral therapy in ? microbiologic diagnosis of osteomyelitis (Option A). The women with PID. This patieltt has tachycardia and a high - patient had a predisposing traumatic injury that healed; fbver; additionally, her nausea raises the concern she may be however, she then experienced progressively worsening pain unable to tolerate oral therapy, so hospitalization is indicated. and has physical flndings of local swelling and tenderness. Organisms irnplicated in PID include Neisserio gonorrhoeae, The elevated erythrocyte sedimentation rate is nonspeciflc; Chl am y dia t racho mat i s, My c ctplasma ge nital i u m, a nd ot he r however, based on the clinical presentation, acute osteomy- endogenous vaginal flora (particularly anaerobes); 15'2, of elitis must be considered. Because her symptom duration cases also include Enterobacteriaceae. Despite the polymicro- is greater than 2 weeks, plain radiography may be used to bial nature of the infbction, cervicaldischarge should be tested investigate the possibility of osteomyelitis. Plain radiographs only fbr N. gonorrhoeoe and C. trachomotis with nucleic acid are not sufficiently sensitive to exclude the diagnosis, but the irnrplification testing. FI)A-approved testing for M. genitalium flndings of cortical destruction accompanied by periosteal is available, but routine testing for women with PID is not reaction, especially when a previous radiograph is available recomnlencied. When the patient has clinically irnproved and for comparison, are sufficiently speciflc to conflrm the diag- can tolerate oral therapy, she can be discl-rarged to complete a nosis and proceed with bone biopsy to establish a micro- total of'14 days of tl-rerapy with oral doxycycline. At presenta- biologic diagnosis and guide antibiotic therapy selection. tion, she should be screened fbr syphilis and HIV. Acute osteomyelitis in adults requires a prolonged therapy The CDC sexually trirnsmitted infection treatment duration (generally 6 weeks), so guiding antibiotic therapy guidelines do not reconlmend amoxicillin-clavulanate and using bone biopsy culture results is optimal to ensure that doxycycline (Option A) for management of PII) in any set- the selected therapy is effective. ting because it has not been studied; moreover, this patierrt Ciprofloxacin and linezolid (Option B, C) are oral antibi- requires a parenteral regimen because of her illness severity. otics with high bioavailability that are potentially important Cefoxitin (or cefotetan) with doxycycline is the other agents in the therapeutic armamentarium for bone infec regimen recommended for inpatient treatment of PID; tion treatment. However, beginning antibiotic therapy is not combining cefoxitin or cefotetan with gentamicin (Option urgent in patients with no signs of concomitant soft tissue B), however. is not recommended. Doxycycline h:rs excel- infection or sepsis, and every effort should be made to con- lent bioavailability; however, bec:ruse this patient reported flrm a microbiologic cause when managing osteomyelitis. nausea, an all-parenteral initial regimen may be optimal. MRI with contrast (Option D) is the imaging modality Parenteral doxycycline can cause significant infusion-site of choice for evaluating osteomyelitis if the plain radiograph reactions (pain, erythema, swelling). is unrevealing. It is not indicated in this patient because the Single-dose ceftriaxone with azithromycin (Option C) flndings on plain radiography are quite speciflc for bone is recommended fbr uncomplicated cervicitis or urethritis infection. In patients who require additional imaging and but is inadequate treatment fbr PID, which is ir tnuch more cannot undergo MRI, contrast-enhanced CT should be serious infection, even ir-r an outpatient. performed. Most women with PID car-r be managed as outpatients. Nuclear medicine studies (Option E) are less sensitive A single dose of ceftriaxone followed by 1a days of doxy and speciflc for the diagnosis of osteomyelitis and should cycline (with or without metronidazole) (Option D) is the only be utilized if MRI or CT cannot be performed. recomnlended outpatient regirnen fbr PID.

microbiologic diagnosis of osteomyelitis (Option A). The women with PID. This patieltt has tachycardia and a high - patient had a predisposing traumatic injury that healed; fbver; additionally, her nausea raises the concern she may be however, she then experienced progressively worsening pain unable to tolerate oral therapy, so hospitalization is indicated. and has physical flndings of local swelling and tenderness. Organisms irnplicated in PID include Neisserio gonorrhoeae, The elevated erythrocyte sedimentation rate is nonspeciflc; Chl am y dia t racho mat i s, My c ctplasma ge nital i u m, a nd ot he r however, based on the clinical presentation, acute osteomy- endogenous vaginal flora (particularly anaerobes); 15'2, of elitis must be considered. Because her symptom duration cases also include Enterobacteriaceae. Despite the polymicro- is greater than 2 weeks, plain radiography may be used to bial nature of the infbction, cervicaldischarge should be tested investigate the possibility of osteomyelitis. Plain radiographs only fbr N. gonorrhoeoe and C. trachomotis with nucleic acid are not sufficiently sensitive to exclude the diagnosis, but the irnrplification testing. FI)A-approved testing for M. genitalium flndings of cortical destruction accompanied by periosteal is available, but routine testing for women with PID is not reaction, especially when a previous radiograph is available recomnlencied. When the patient has clinically irnproved and for comparison, are sufficiently speciflc to conflrm the diag- can tolerate oral therapy, she can be discl-rarged to complete a nosis and proceed with bone biopsy to establish a micro- total of'14 days of tl-rerapy with oral doxycycline. At presenta- biologic diagnosis and guide antibiotic therapy selection. tion, she should be screened fbr syphilis and HIV. Acute osteomyelitis in adults requires a prolonged therapy The CDC sexually trirnsmitted infection treatment duration (generally 6 weeks), so guiding antibiotic therapy guidelines do not reconlmend amoxicillin-clavulanate and using bone biopsy culture results is optimal to ensure that doxycycline (Option A) for management of PII) in any set- the selected therapy is effective. ting because it has not been studied; moreover, this patierrt Ciprofloxacin and linezolid (Option B, C) are oral antibi- requires a parenteral regimen because of her illness severity. otics with high bioavailability that are potentially important Cefoxitin (or cefotetan) with doxycycline is the other agents in the therapeutic armamentarium for bone infec regimen recommended for inpatient treatment of PID; tion treatment. However, beginning antibiotic therapy is not combining cefoxitin or cefotetan with gentamicin (Option urgent in patients with no signs of concomitant soft tissue B), however. is not recommended. Doxycycline h:rs excel- infection or sepsis, and every effort should be made to con- lent bioavailability; however, bec:ruse this patient reported flrm a microbiologic cause when managing osteomyelitis. nausea, an all-parenteral initial regimen may be optimal. MRI with contrast (Option D) is the imaging modality Parenteral doxycycline can cause significant infusion-site of choice for evaluating osteomyelitis if the plain radiograph reactions (pain, erythema, swelling). is unrevealing. It is not indicated in this patient because the Single-dose ceftriaxone with azithromycin (Option C) flndings on plain radiography are quite speciflc for bone is recommended fbr uncomplicated cervicitis or urethritis infection. In patients who require additional imaging and but is inadequate treatment fbr PID, which is ir tnuch more cannot undergo MRI, contrast-enhanced CT should be serious infection, even ir-r an outpatient. performed. Most women with PID car-r be managed as outpatients. Nuclear medicine studies (Option E) are less sensitive A single dose of ceftriaxone followed by 1a days of doxy and speciflc for the diagnosis of osteomyelitis and should cycline (with or without metronidazole) (Option D) is the only be utilized if MRI or CT cannot be performed. recomnlended outpatient regirnen fbr PID. 185

Answers and Critiques KIY POI lITS 6 weeks ago; therefore, it is unlikely that early infection has o In women with pelvic inflammatory disease, signs of been missed with testing (Option C). severe systemic toxicity or an inability to tolerate oral r(EY POtl{TS antibiotics, pregnancy, tubo-ovarian abscess, inability . A positive result on the fourth-generation HIV-ll2 to exclude a surgical emergency, and failed outpatient antigen/antibody combination assay but negative antibiotic therapy are indications for hospitalization result on HIV antibody differentiation is tested for and parenteral therapy. HIV RNA by nucleic acid amplification testing; if posi- . Combination cefotetan or cefoxitin plus doxycycline tive, acute HIV infection is confirmed, and a negative or combination clindamycin plus gentamicin are the result identifies a false-positive combination assay. preferred parenteral antibiotic regimens for patients o Postexposure prophylaxis should be started as soon as hospitalized with pelvic inflammatory disease. possible after exposur€; it is not recommended if F - more than72 hours have passed. G t 6 dt Bibliography Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl Bibliography et J Med. 201 5 37 2:2039 48. I PMID : 259927 48] doi 10. 1 056 / NEJMral4l7426 ; :

severe systemic toxicity or an inability to tolerate oral r(EY POtl{TS antibiotics, pregnancy, tubo-ovarian abscess, inability . A positive result on the fourth-generation HIV-ll2 to exclude a surgical emergency, and failed outpatient antigen/antibody combination assay but negative antibiotic therapy are indications for hospitalization result on HIV antibody differentiation is tested for and parenteral therapy. HIV RNA by nucleic acid amplification testing; if posi- . Combination cefotetan or cefoxitin plus doxycycline tive, acute HIV infection is confirmed, and a negative or combination clindamycin plus gentamicin are the result identifies a false-positive combination assay. preferred parenteral antibiotic regimens for patients o Postexposure prophylaxis should be started as soon as hospitalized with pelvic inflammatory disease. possible after exposur€; it is not recommended if F - more than72 hours have passed. G t 6 dt Bibliography Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl Bibliography et J Med. 201 5 37 2:2039 48. I PMID : 259927 48] doi 10. 1 056 / NEJMral4l7426 ; : *- AD Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory testing for the diagnosis of HIV infection: & updated recommendations. Published June 27.2014. Available at http:// C= Item 93 Answer: D dx.doi.org/ 10.15620 /cdc.23447. Accessed April 17. 2020. rl *! IC Educational Objective: Identiff false-positive HIV test sr results. -Gtt* t* Item 94 Answer: A The most appropriate management is to reinforce safe sexual Ed ucationa I Objective: Diagnose neurocysticercosis. practice counseling (Option D). According to an algorithm from the CDC, this screening test was a false positive. Fourth The most likely diagnosis is neurocysticercosis (Option A), generation HIV testing uses a combination assay for HIV which causes up to 30% of seizure events in endemic regions antibody and HIV p24 antigen, which detects acute infection (Central and South America, India, sub-saharan Africa). Neu- at least 1 week earlier than older assays. A positive result on rocysticercosis is caused by ingesting eggs of the pork tape- the combination assay leads to testing with an HIV 1/HIV-2 worrn Taenia solium in food or water contaminated by a t antibody differentiation immunoassay, which, if positive, human carrier of the parasite. Neurocysticercosis can present conflrms infection. Specimens that test positive on the initial with viable parenchymal cysts, calcifled nonviable paren- combination assay but negative for HIV antibody are tested chymal lesions, intraventricular cysts, or subarachnoid cysts. for HIV RNA by nucleic acid ampliflcation testing; if positive, This patient has a viable parenchymal cyst with surrounding acute HIV infection is conflrmed, and a negative result iden- cerebral edema. Seizure is the most common presentation tifles a false-positive HIV antibody and HIV p24 combination of neurocysticercosis. Treatment includes managing sei- assay. Although the initial combination assay has a 99.6'/. zures and increased intracranial pressure and administering speciflcity, testing in low prevalence populations can result adjunctive glucocorticoids and antiparasitic agents for viable in false positives, so waiting for the results of the conflrma cystic lesions. tory antibody diflerentiation immunoassay and nucleic acid Primary central nervous system lymphoma (PCNSL) ampliflcation testing is important. This patient does not have (Option B) initially occurs without systemic or lymph node HIV infection, and safe sexual practice counseling should be involvement. Immunodeflciency is the most consistent risk reinforced. factor, but PCNSL incidence is increasing in older, immu- CD4 cell counts are useful in patients with a new diag- nocompetent patients. On MRI, PCNSL appears as a single, nosis of HIV infection in determining the nadir CD4 cell well-demarcated, deep white matter (periventricular) lesion count before treatment initiation and in determining oppor- with minimal mass eflect or edema. The patient's history tunistic infection prophylaxis strategies (Option A). Because and MRI findings do not support PCNSL. this patient does not have HIV infection, it would not be Brain abscesses (OptionC) can occurin immunocompe- useful to perform this test. tent or immunosuppressed persons and are most commonly Six weeks have passed since this patient's sexual seen in men. The most common predisposing conditions in encounter, so postexposure prophylaxis is not indicated immunocompetent patients include the presence of con- (Option B). When given, prophylaxis should be started as tiguous foci of infection such as sinusitis (frontal lobe) and soon as possible after exposure; it is not recommended if otitis media (temporal lobe or cerebellum); hematogenous more than72 hours have passed. spread, often from an odontogenic process, endocarditis, or Following HIV exposure, detectable viremia develops 10 injection drug use; and following neurosurgery or trauma. to 15 days after infection, and screening tests become posi- Headache is the most common symptom, whereas fever tive approximately 5 days later. Early testing after exposure is present in about half of patients, and seizure may occur may not detect HIV infection, and repeat testing 2 weeks in about 25'L of patients. MRI may show central necro- later is recommended. However, this patient's exposure was sis, ring-enhancing lesion, and edema. This patient has no

*- AD Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory testing for the diagnosis of HIV infection: & updated recommendations. Published June 27.2014. Available at http:// C= Item 93 Answer: D dx.doi.org/ 10.15620 /cdc.23447. Accessed April 17. 2020. rl *! IC Educational Objective: Identiff false-positive HIV test sr results. -Gtt* t* Item 94 Answer: A The most appropriate management is to reinforce safe sexual Ed ucationa I Objective: Diagnose neurocysticercosis. practice counseling (Option D). According to an algorithm from the CDC, this screening test was a false positive. Fourth The most likely diagnosis is neurocysticercosis (Option A), generation HIV testing uses a combination assay for HIV which causes up to 30% of seizure events in endemic regions antibody and HIV p24 antigen, which detects acute infection (Central and South America, India, sub-saharan Africa). Neu- at least 1 week earlier than older assays. A positive result on rocysticercosis is caused by ingesting eggs of the pork tape- the combination assay leads to testing with an HIV 1/HIV-2 worrn Taenia solium in food or water contaminated by a t antibody differentiation immunoassay, which, if positive, human carrier of the parasite. Neurocysticercosis can present conflrms infection. Specimens that test positive on the initial with viable parenchymal cysts, calcifled nonviable paren- combination assay but negative for HIV antibody are tested chymal lesions, intraventricular cysts, or subarachnoid cysts. for HIV RNA by nucleic acid ampliflcation testing; if positive, This patient has a viable parenchymal cyst with surrounding acute HIV infection is conflrmed, and a negative result iden- cerebral edema. Seizure is the most common presentation tifles a false-positive HIV antibody and HIV p24 combination of neurocysticercosis. Treatment includes managing sei- assay. Although the initial combination assay has a 99.6'/. zures and increased intracranial pressure and administering speciflcity, testing in low prevalence populations can result adjunctive glucocorticoids and antiparasitic agents for viable in false positives, so waiting for the results of the conflrma cystic lesions. tory antibody diflerentiation immunoassay and nucleic acid Primary central nervous system lymphoma (PCNSL) ampliflcation testing is important. This patient does not have (Option B) initially occurs without systemic or lymph node HIV infection, and safe sexual practice counseling should be involvement. Immunodeflciency is the most consistent risk reinforced. factor, but PCNSL incidence is increasing in older, immu- CD4 cell counts are useful in patients with a new diag- nocompetent patients. On MRI, PCNSL appears as a single, nosis of HIV infection in determining the nadir CD4 cell well-demarcated, deep white matter (periventricular) lesion count before treatment initiation and in determining oppor- with minimal mass eflect or edema. The patient's history tunistic infection prophylaxis strategies (Option A). Because and MRI findings do not support PCNSL. this patient does not have HIV infection, it would not be Brain abscesses (OptionC) can occurin immunocompe- useful to perform this test. tent or immunosuppressed persons and are most commonly Six weeks have passed since this patient's sexual seen in men. The most common predisposing conditions in encounter, so postexposure prophylaxis is not indicated immunocompetent patients include the presence of con- (Option B). When given, prophylaxis should be started as tiguous foci of infection such as sinusitis (frontal lobe) and soon as possible after exposure; it is not recommended if otitis media (temporal lobe or cerebellum); hematogenous more than72 hours have passed. spread, often from an odontogenic process, endocarditis, or Following HIV exposure, detectable viremia develops 10 injection drug use; and following neurosurgery or trauma. to 15 days after infection, and screening tests become posi- Headache is the most common symptom, whereas fever tive approximately 5 days later. Early testing after exposure is present in about half of patients, and seizure may occur may not detect HIV infection, and repeat testing 2 weeks in about 25'L of patients. MRI may show central necro- later is recommended. However, this patient's exposure was sis, ring-enhancing lesion, and edema. This patient has no 186

Answers and Critiques predisposing condition for brain abscess or imaging features Another option for fulminant CDI infection is combined consistent with that diagnosis. oral vancomycin. i ntravenous metronid azole. a nd rectal van Cerebral toxoplasmosis (Option D) is lypically found comycin when ileus is present (Option C). This patient does in immunosuppressed persons, including patients with not have fulminant CDI; therefore, this combination therapy HIV infection or transplant recipients. Clinical presenta- is not indicated. tion includes headache, fever in approximately half of all Tapered and pulsecl vancomycin therapy (Option D) patients, and focal neurologic deficits. MRI brain imaging consists of oral vancomycin, 125 mg fbur times daily for reveals multiple ring enhancing lesions. This pattern is not 10 days, then i25 mg twice daily for 7 days, then 125 mg consistent with the patient's presentation. every 2 or 3 days fbr 2 to B lteeks. Tapered and pulsed van comycin therapy is an indicated therapeutic option for flrst KEY POITITg and subsequent CDI recurrences if the initial episode was o Seizure is the most common presentation of neuro- treated with standard therapy consisting of vancomycin or cysticercosis. fidaxomicin. UI o Neurocysticercosis can present with viable parenchymal o J l(tY P0rlrTs ET cysts, calcified nonviable parenchymal lesions, intra- P ventricular cysts, or subarachnoid cysts. . Severe CDI is defined by a leukocyte count of 15,000/prl a- L (tS x tOell) or greater or a serum creatinine level of L' 1.5 mg/dl (133 pmol/L) or greater. g =, Bibliography .E White AC Jr, Coyle CM, Rajshekhar V et al. Diagnosis and treatment of neu . Oral fidaxomicin or vancomycin is recommended to |a L rocysticercosis: 2017 clinical practice guidelines by the Infectious o treat an initial episode of nonsevere or severe Diseases Society of America (IDSA) and the American Society of Tropical l,t Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018;66:1159 1163. Clostridioi des dfficile infection. = L IPMID: Zg 1tlZ\tl doi:10.1 093 /cid/ciy157

predisposing condition for brain abscess or imaging features Another option for fulminant CDI infection is combined consistent with that diagnosis. oral vancomycin. i ntravenous metronid azole. a nd rectal van Cerebral toxoplasmosis (Option D) is lypically found comycin when ileus is present (Option C). This patient does in immunosuppressed persons, including patients with not have fulminant CDI; therefore, this combination therapy HIV infection or transplant recipients. Clinical presenta- is not indicated. tion includes headache, fever in approximately half of all Tapered and pulsecl vancomycin therapy (Option D) patients, and focal neurologic deficits. MRI brain imaging consists of oral vancomycin, 125 mg fbur times daily for reveals multiple ring enhancing lesions. This pattern is not 10 days, then i25 mg twice daily for 7 days, then 125 mg consistent with the patient's presentation. every 2 or 3 days fbr 2 to B lteeks. Tapered and pulsed van comycin therapy is an indicated therapeutic option for flrst KEY POITITg and subsequent CDI recurrences if the initial episode was o Seizure is the most common presentation of neuro- treated with standard therapy consisting of vancomycin or cysticercosis. fidaxomicin. UI o Neurocysticercosis can present with viable parenchymal o J l(tY P0rlrTs ET cysts, calcified nonviable parenchymal lesions, intra- P ventricular cysts, or subarachnoid cysts. . Severe CDI is defined by a leukocyte count of 15,000/prl a- L (tS x tOell) or greater or a serum creatinine level of L' 1.5 mg/dl (133 pmol/L) or greater. g =, Bibliography .E White AC Jr, Coyle CM, Rajshekhar V et al. Diagnosis and treatment of neu . Oral fidaxomicin or vancomycin is recommended to |a L rocysticercosis: 2017 clinical practice guidelines by the Infectious o treat an initial episode of nonsevere or severe Diseases Society of America (IDSA) and the American Society of Tropical l,t Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018;66:1159 1163. Clostridioi des dfficile infection. = L IPMID: Zg 1tlZ\tl doi:10.1 093 /cid/ciy157 Bibliography McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Item 95 Answer: B Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare EX Educational Objective: Treat a first episode of severe Epidemiologz of America (SHEA). Clin Infect Dis. 2018;66:987 994. lpUtn, 295622661 doi:10.1093 /c id I ciy749 Clo stridioides dfficile infection.

Bibliography McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Item 95 Answer: B Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare EX Educational Objective: Treat a first episode of severe Epidemiologz of America (SHEA). Clin Infect Dis. 2018;66:987 994. lpUtn, 295622661 doi:10.1093 /c id I ciy749 Clo stridioides dfficile infection. 'llris patient has an initial episode of severe Closfridioides diJficile infection (CDl). which should be treated with oral Item 96 Answer: B fidaxomicin therapy (Option B). Antibiotic use is the strong Educational Objective: Treat a human bite in a patient est risk factor fbr CDI. It is most highly associated with who is allergic to penicillin. antimicrobial agents that have activity against anaerobic colonic flora but are not ellective against C. difficile (such as This patient has diabetes mellitus and is immunocompro- clindamycin). Antibiotic-associated diarrhea in these cases mised, so she should receive antibiotic prophylaxis with levo- is thought to occur by suppression ol'the intestinal microbi floxacin and metronidazole (Option B) following a human ota. r,vith resultant overgrowth of C. difficile organisms and bite to the hand. Oral amoxicillin-clavulanate (Option A), the production of toxin (toxins A and B). In all cases of CDI, the preferred agent, is contraindicated because of her history of culprit antibiotic should be stopped if possible. All patients anaphylaxis following penicillin use. The microbiologr associ with conlirmed CDI require antimicrobial treatment, but ated with the human mouth and skin includes aerobic bacteria optin-ral managernent depends on whether the episode rep- such as Eikenella corrodens, streptococci, and staphylococci resents an initial infection or first or second recurrence and as well as anaerobic bacteria, including Fusobacterium, Pep on the severity of disease (nonsevere. severe. fulminant). tostreptococcus, and Preu otella species. Alternative regimens Severe CDI is definecl by a leukocyte count of 15,000rpl with similar coverage to amoxicillin-cla'u.ulanate include tri- (15 x 10eil) or greater or a serum creatinine level of 1.5 mg/ methoprim sulfamethoxazole, a fluoroquinolone like cipro- dt- (133 pmolrt.) or greater. The 2017 Infectious Diseases floxacin or levofloxacin, or doxycycline plus clindamycin or Society of America and Society fbr Healthcare Epidemiolory metronidazole. Monotherapy with moxifloxacin, which has of America clinical practice guideline for CDI recommends anaerobic activity, can be considered as well. Although anti- either oral fidaxomicin or oral vancomycin fbr patients with biotic prophylaxis is not routinely recommended (Option D) nonsevere or severe CDI. after a human bite, this patient's immunocompromised state Intravenous metroniclazole monotherapy (Option A) is and the involvement of the hand increase the risk of infection not an indicated treatment fbr any degree of CDI severity or and warrant antibiotic prophylaxis. In addition to immu initial or recurrent disease status. Intravenous metronidazole nocompromise and hand involvement, other factors that therapy combined r,r,ith oral vancomycin is an indicated increase the risk of infection include wounds with associated regimen fbr fuhninant Cf)l which is associated rvith hypo edema or lymphatic or venous insufficienc!; crush injury; tension, shock, ileus. or megacolon. Patients with fulminant wounds involving a joint or bone; deep puncture wounds; or disease also warrant surgical evaluation. wounds involving the face or genitalia. A 3- to S-day course of

'llris patient has an initial episode of severe Closfridioides diJficile infection (CDl). which should be treated with oral Item 96 Answer: B fidaxomicin therapy (Option B). Antibiotic use is the strong Educational Objective: Treat a human bite in a patient est risk factor fbr CDI. It is most highly associated with who is allergic to penicillin. antimicrobial agents that have activity against anaerobic colonic flora but are not ellective against C. difficile (such as This patient has diabetes mellitus and is immunocompro- clindamycin). Antibiotic-associated diarrhea in these cases mised, so she should receive antibiotic prophylaxis with levo- is thought to occur by suppression ol'the intestinal microbi floxacin and metronidazole (Option B) following a human ota. r,vith resultant overgrowth of C. difficile organisms and bite to the hand. Oral amoxicillin-clavulanate (Option A), the production of toxin (toxins A and B). In all cases of CDI, the preferred agent, is contraindicated because of her history of culprit antibiotic should be stopped if possible. All patients anaphylaxis following penicillin use. The microbiologr associ with conlirmed CDI require antimicrobial treatment, but ated with the human mouth and skin includes aerobic bacteria optin-ral managernent depends on whether the episode rep- such as Eikenella corrodens, streptococci, and staphylococci resents an initial infection or first or second recurrence and as well as anaerobic bacteria, including Fusobacterium, Pep on the severity of disease (nonsevere. severe. fulminant). tostreptococcus, and Preu otella species. Alternative regimens Severe CDI is definecl by a leukocyte count of 15,000rpl with similar coverage to amoxicillin-cla'u.ulanate include tri- (15 x 10eil) or greater or a serum creatinine level of 1.5 mg/ methoprim sulfamethoxazole, a fluoroquinolone like cipro- dt- (133 pmolrt.) or greater. The 2017 Infectious Diseases floxacin or levofloxacin, or doxycycline plus clindamycin or Society of America and Society fbr Healthcare Epidemiolory metronidazole. Monotherapy with moxifloxacin, which has of America clinical practice guideline for CDI recommends anaerobic activity, can be considered as well. Although anti- either oral fidaxomicin or oral vancomycin fbr patients with biotic prophylaxis is not routinely recommended (Option D) nonsevere or severe CDI. after a human bite, this patient's immunocompromised state Intravenous metroniclazole monotherapy (Option A) is and the involvement of the hand increase the risk of infection not an indicated treatment fbr any degree of CDI severity or and warrant antibiotic prophylaxis. In addition to immu initial or recurrent disease status. Intravenous metronidazole nocompromise and hand involvement, other factors that therapy combined r,r,ith oral vancomycin is an indicated increase the risk of infection include wounds with associated regimen fbr fuhninant Cf)l which is associated rvith hypo edema or lymphatic or venous insufficienc!; crush injury; tension, shock, ileus. or megacolon. Patients with fulminant wounds involving a joint or bone; deep puncture wounds; or disease also warrant surgical evaluation. wounds involving the face or genitalia. A 3- to S-day course of 187

Answers and Critiques antibiotic prophylaxis is recommended. Surgical evaluation cryptococcal infection can occur in heirlthy persons. most for possible debridement and removal of foreign bodies is inf'ected patients have advanced immune sllppression. Cryp particularly important with hand bites. Radiographs may tococcal int'ection most comnrclnly manif'ests as central ner demonstrate fracture, other bony involvement, or foreign vous system infection. C. necfbrmons is not associated with bodies. catheter- :rssociatecl in f'ections. Human bite wounds are prone to tetanus infection, but Hisfoplosrno copsurlotunr (Option D) is not associated this patient received the tetanus toxoid, reduced diphtheria with hospital-acquirecl inf'ections. It is acquired by inhala- toxoid, and acellular pertussis vaccine (Tdap) 1 year ago and tion ancl primarily produces an asymptomatic pulmonary does not require repeat immunization now. In addition to inf-ection. When it is fbund in the bloodstream. p:rtients rtre assessment for tetanus prophylaxis (Option C), evaluation often immunosuppressed or of advancecl age. The symptoms of human bites for potential exposure to hepatitis B and C of' clisseminated histoplasmosis may include lymphadenop viruses, HIV and other bodily fluid-transmitted pathogens athll hepatosplenomegaly. skin and mucosal lesions. ancl is warranted. central nen'olls system symptoms. J ur XEY POIl{T3 t(EY POtt{TS .D = - UI o Antibiotic prophylaxis is indicated following a human . Commonly encountered risk factors for candidemia o, bite involving the hand or in immunocompromised include central venous or hemodialysis-associated J CL patients. catheters, gastrointestinal surgery and broad-spectrum n o In patients not allergic to penicillin requiring antibiotic antimicrobial agents. =. ai o The T2 magnetic resonance assay of whole blood and sl? prophylaxis following a human bite, amoxicillin- (D clavulanate is preferred. the B-D-glucan assay for invasive candidiasis should l,! be obtained when a patient at high risk receiving Bibliography antimicrobial agents is not responding to therapy. Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society Bibliography of America. Clin Infect Dis. 2014;59:e10-52. [PMID: ZqgZSqZZl doi:10. Pappas PG, Kauffman CA, Andes DR, et al. Executive summary: clinical 1093lcidlciu444 practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:4O9-17. [PMIO, ZOetO+tg] doi:10.1093/cid/civll94

antibiotic prophylaxis is recommended. Surgical evaluation cryptococcal infection can occur in heirlthy persons. most for possible debridement and removal of foreign bodies is inf'ected patients have advanced immune sllppression. Cryp particularly important with hand bites. Radiographs may tococcal int'ection most comnrclnly manif'ests as central ner demonstrate fracture, other bony involvement, or foreign vous system infection. C. necfbrmons is not associated with bodies. catheter- :rssociatecl in f'ections. Human bite wounds are prone to tetanus infection, but Hisfoplosrno copsurlotunr (Option D) is not associated this patient received the tetanus toxoid, reduced diphtheria with hospital-acquirecl inf'ections. It is acquired by inhala- toxoid, and acellular pertussis vaccine (Tdap) 1 year ago and tion ancl primarily produces an asymptomatic pulmonary does not require repeat immunization now. In addition to inf-ection. When it is fbund in the bloodstream. p:rtients rtre assessment for tetanus prophylaxis (Option C), evaluation often immunosuppressed or of advancecl age. The symptoms of human bites for potential exposure to hepatitis B and C of' clisseminated histoplasmosis may include lymphadenop viruses, HIV and other bodily fluid-transmitted pathogens athll hepatosplenomegaly. skin and mucosal lesions. ancl is warranted. central nen'olls system symptoms. J ur XEY POIl{T3 t(EY POtt{TS .D = - UI o Antibiotic prophylaxis is indicated following a human . Commonly encountered risk factors for candidemia o, bite involving the hand or in immunocompromised include central venous or hemodialysis-associated J CL patients. catheters, gastrointestinal surgery and broad-spectrum n o In patients not allergic to penicillin requiring antibiotic antimicrobial agents. =. ai o The T2 magnetic resonance assay of whole blood and sl? prophylaxis following a human bite, amoxicillin- (D clavulanate is preferred. the B-D-glucan assay for invasive candidiasis should l,! be obtained when a patient at high risk receiving Bibliography antimicrobial agents is not responding to therapy. Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society Bibliography of America. Clin Infect Dis. 2014;59:e10-52. [PMID: ZqgZSqZZl doi:10. Pappas PG, Kauffman CA, Andes DR, et al. Executive summary: clinical 1093lcidlciu444 practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:4O9-17. [PMIO, ZOetO+tg] doi:10.1093/cid/civll94 Item 97 tr Answer: B Educational Objective: Diagnose a patient with Item 98 Answer: A candidemia. Ed ucati o na I O bjective : Diagnose coccidioidomycosis. '[he most likely callse of this patient's finclings rrould be This patient has a coccidioidomycosis pulmonary infection Condidcr crlbicons infection (Option B).The presence of'yeast (Option A). The fungus Coccidioides is inhaled and produces a cells in the blood and on the catheter indicates candidemia. pulmonary infection. In endemic areas (Southern California, Commonl_v encountered risk f'actors tbr candidemia inclnde Arizona, New Mexico, Texas), Coccidioides species cause up central venous or hemodiitll,'sis-associated catheters. gastro- to 25% of community-acquired pneumonia (CAP) cases. In intesti nal surgery. hroad- spectrum ant imicrobi al agents. I CU healthy persons, the initial infection is generally contained. stay or mechanical ventilirtion lor more than :l dirys. tr:rns However, immunocompromised persons are at risk for plantation. and neutropenia. Onlv -10'/,, to 60'1, of pirtients dissemination. The differential diagnosis for pulmonary coc- have positive blood culture results. The T2 mappetic resonance cidioidomycosis includes bacterial pneumonia, tuberculosis, rrssay of'whole blood provides r.rpid diagnosis of culture histoplasmosis, and sarcoidosis. Diagnosis is straightforward negative invasile candidal intbctions. The p-D glucan asru), in endemic areas and is usually based on clinical manifes- can be used also to diagnose invasive cirndidiasis in patients tations and conflrmatory testing by a mycologic culture of -lhese rnith negative bloocl culture results. ass:rys should be affected tissue, histopathologic evaluation of tissue, serologr obtainetl rryhen a pirtient at high risk receiving antimicrobiirl for Coccidioides antibodies, or urinary antigen testing. Flu- agents is not responding to therapy: conazole is flrst-line treatment for symptomatic infection. In Blcrsfomyces dermofiticlis (Option A) is r:rrely seen in patients with meningitis, fluconazole is continued for life. In the bloodstream unless it is associrrted rtith inf'ection in a patients who do not respond to azoles, intrathecal amphoter- severely immunosuppressecl person. such rrs rr stem cell or icin B may be an alternative. solid organ transplant recipient. Int'ection occurs by inha- Klebsiella pneumoniae (Option B) is a common lirtion of coniditr and manilbsts initialll'' as a primar)' pul- gram-negative pathogen producing CAP although it is not monary infection (:rcute or chronic pneumonia). It is not the most commonly identifled organism. Suggestive clinical associateel wit h catheter- rel ated in fbct ions. symptoms include fever, cough, sputum production, and Cryptococcus neofornrcrns (Option C) is an enclpsn- dyspnea. Radiographic flndings canbe characterized as lobar lated yeast that may be seen in the bkrodstream. Although or multilobar consolidation or cavitary lesions. However,

Item 97 tr Answer: B Educational Objective: Diagnose a patient with Item 98 Answer: A candidemia. Ed ucati o na I O bjective : Diagnose coccidioidomycosis. '[he most likely callse of this patient's finclings rrould be This patient has a coccidioidomycosis pulmonary infection Condidcr crlbicons infection (Option B).The presence of'yeast (Option A). The fungus Coccidioides is inhaled and produces a cells in the blood and on the catheter indicates candidemia. pulmonary infection. In endemic areas (Southern California, Commonl_v encountered risk f'actors tbr candidemia inclnde Arizona, New Mexico, Texas), Coccidioides species cause up central venous or hemodiitll,'sis-associated catheters. gastro- to 25% of community-acquired pneumonia (CAP) cases. In intesti nal surgery. hroad- spectrum ant imicrobi al agents. I CU healthy persons, the initial infection is generally contained. stay or mechanical ventilirtion lor more than :l dirys. tr:rns However, immunocompromised persons are at risk for plantation. and neutropenia. Onlv -10'/,, to 60'1, of pirtients dissemination. The differential diagnosis for pulmonary coc- have positive blood culture results. The T2 mappetic resonance cidioidomycosis includes bacterial pneumonia, tuberculosis, rrssay of'whole blood provides r.rpid diagnosis of culture histoplasmosis, and sarcoidosis. Diagnosis is straightforward negative invasile candidal intbctions. The p-D glucan asru), in endemic areas and is usually based on clinical manifes- can be used also to diagnose invasive cirndidiasis in patients tations and conflrmatory testing by a mycologic culture of -lhese rnith negative bloocl culture results. ass:rys should be affected tissue, histopathologic evaluation of tissue, serologr obtainetl rryhen a pirtient at high risk receiving antimicrobiirl for Coccidioides antibodies, or urinary antigen testing. Flu- agents is not responding to therapy: conazole is flrst-line treatment for symptomatic infection. In Blcrsfomyces dermofiticlis (Option A) is r:rrely seen in patients with meningitis, fluconazole is continued for life. In the bloodstream unless it is associrrted rtith inf'ection in a patients who do not respond to azoles, intrathecal amphoter- severely immunosuppressecl person. such rrs rr stem cell or icin B may be an alternative. solid organ transplant recipient. Int'ection occurs by inha- Klebsiella pneumoniae (Option B) is a common lirtion of coniditr and manilbsts initialll'' as a primar)' pul- gram-negative pathogen producing CAP although it is not monary infection (:rcute or chronic pneumonia). It is not the most commonly identifled organism. Suggestive clinical associateel wit h catheter- rel ated in fbct ions. symptoms include fever, cough, sputum production, and Cryptococcus neofornrcrns (Option C) is an enclpsn- dyspnea. Radiographic flndings canbe characterized as lobar lated yeast that may be seen in the bkrodstream. Although or multilobar consolidation or cavitary lesions. However, 188

Answers and Criti ques indolent symptoms lasting for more than a month would be Tuberculosis (Option C) can cause a subacute uncharacteristic of lung infection caused by pneumoniae. menin_ K. gitis with cranial nerve palsies resulting from basilar Primary pulmonary tuberculosis may be confused men_ with ingitis. Tuberculous meningitis would be more likely in pulmonary coccidioidomycosis early in the this disease course. patient if he had a low CSF glucose level, elevated protein The symptomatologz is similar, and pulmonary tuberculosis level, and mental status changes. Cranial neuropathies must be ruled out. However, Mycobacterium tuberculosis and long tract signs can be observed in patients with infection (Option C) does not typically present as tubercular a mid_ basilar meningitis (with or without hydrocephalus or dle lobe inflltrate. Negative sputum acid_fast bacilli tuber_ stains culomas). and cultures would exclude pulmonary tuberculosis in this West Nile meningitis (Option D) can present with patient. a sim_ ilar CSF proflle to Lyme meningitis in endemic areas during Sarcoidosis (Option D) is a systemic granulomatous the summer and fall but has a more acute presentation. disease of unknown origin. It is more frequent in younger West Nile virus can present as meningitis, encephalitis, or Black adults, especially women. It usually presents in the acute flaccid paralysis. A maculopapular rash may be seen, U! respiratory tract as bilateral hilar lymphadenopathy, with o and patients usually report mosquito bites in the preceding or without diffuse parenchymal lung changes. Sarcoidosis weeks. In patients with encephalitis, basal ganglia involve J ET .I is typically an indolent process, presenting over several ment (tremor, rigidity, postural instability, bradykinesia) is P L months to years, with progressive cough and dyspnea. a clue. Isolated facial palsy in West Nile meningitis is rare. U ?t I(EY POIilT E r(EY P0ll{TS .E o Coccidioides species cause up to 2Sol, of community_ t,l . Lyme meningitis may be indistinguishable from viral L (l, acquired pneumonia in endemic areas (Southern meningitis, with fever, headache, and meningismus. UI California, Arizona, New Mexico, Texas). = E . The "rule of 7s" can help classiSr a patient at low risk of having Lyme disease (headache duration <7 days, Bibliography <7O"1, mononuclear cells in the cerebrospinal fluid, Galgiani JN, Ampel NM, Blair JE, et al. Executive Summary: 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline fbr the and absence of a seventh facial nerve palsy). treatment of coccidioidomycosis. Clin Infect Dis. 2016 Sep 15;63(6): 717 22. doi: 10.1093/cid/ciw53S Bibliography Garcia-Monco JC, Benach JL. Lyme neuroborreliosis: clinical outcomes, con- Item 99 Answer: B troversy, pathogenesis. and polymicrobial infections. Ann Neurol. 2Ol9: 85:21-31. [PMID: :OSeO+Zt] doi:10.1002/ana.25389 Ed ucationa I Objective: Diagnose Lyme meningitis.

indolent symptoms lasting for more than a month would be Tuberculosis (Option C) can cause a subacute uncharacteristic of lung infection caused by pneumoniae. menin_ K. gitis with cranial nerve palsies resulting from basilar Primary pulmonary tuberculosis may be confused men_ with ingitis. Tuberculous meningitis would be more likely in pulmonary coccidioidomycosis early in the this disease course. patient if he had a low CSF glucose level, elevated protein The symptomatologz is similar, and pulmonary tuberculosis level, and mental status changes. Cranial neuropathies must be ruled out. However, Mycobacterium tuberculosis and long tract signs can be observed in patients with infection (Option C) does not typically present as tubercular a mid_ basilar meningitis (with or without hydrocephalus or dle lobe inflltrate. Negative sputum acid_fast bacilli tuber_ stains culomas). and cultures would exclude pulmonary tuberculosis in this West Nile meningitis (Option D) can present with patient. a sim_ ilar CSF proflle to Lyme meningitis in endemic areas during Sarcoidosis (Option D) is a systemic granulomatous the summer and fall but has a more acute presentation. disease of unknown origin. It is more frequent in younger West Nile virus can present as meningitis, encephalitis, or Black adults, especially women. It usually presents in the acute flaccid paralysis. A maculopapular rash may be seen, U! respiratory tract as bilateral hilar lymphadenopathy, with o and patients usually report mosquito bites in the preceding or without diffuse parenchymal lung changes. Sarcoidosis weeks. In patients with encephalitis, basal ganglia involve J ET .I is typically an indolent process, presenting over several ment (tremor, rigidity, postural instability, bradykinesia) is P L months to years, with progressive cough and dyspnea. a clue. Isolated facial palsy in West Nile meningitis is rare. U ?t I(EY POIilT E r(EY P0ll{TS .E o Coccidioides species cause up to 2Sol, of community_ t,l . Lyme meningitis may be indistinguishable from viral L (l, acquired pneumonia in endemic areas (Southern meningitis, with fever, headache, and meningismus. UI California, Arizona, New Mexico, Texas). = E . The "rule of 7s" can help classiSr a patient at low risk of having Lyme disease (headache duration <7 days, Bibliography <7O"1, mononuclear cells in the cerebrospinal fluid, Galgiani JN, Ampel NM, Blair JE, et al. Executive Summary: 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline fbr the and absence of a seventh facial nerve palsy). treatment of coccidioidomycosis. Clin Infect Dis. 2016 Sep 15;63(6): 717 22. doi: 10.1093/cid/ciw53S Bibliography Garcia-Monco JC, Benach JL. Lyme neuroborreliosis: clinical outcomes, con- Item 99 Answer: B troversy, pathogenesis. and polymicrobial infections. Ann Neurol. 2Ol9: 85:21-31. [PMID: :OSeO+Zt] doi:10.1002/ana.25389 Ed ucationa I Objective: Diagnose Lyme meningitis. The most likely diagnosis is Borrelia burgdorferi meningitis Item 100 Answer: C (Option B). The flrst stage of Lyme disease usually presents Educational Objective: Treat cystitis during pregnancy. with a flu-like illness 7 to 4 weeks after infection. character- ized by an erythema migrans rash. Focal cardiac or neurologic Cystitis in a pregnant woman is considered a complicated symptoms may also occur in early disseminated disease, typ- urinary tract infection and requires a urine culture and ically 2 to 10 weeks following the development of the rash. prompt treatment with antibiotics; cefpodoxime proxetil is Although Lyme meningitis can involve any cranial nerve, an acceptable and safe choice in pregnant women (Option facial nerve palsy is the most common manifestation, occur- C), as are other cephalosporin agents (cephalexin, cefdinir) ring in B'2, of patients with Lyme disease. I-yme disease causes and amoxicillin-clavulanate. Physiologic alterations in the a lymphocytic meningitis that may be indistinguishable from urinary tract beginning early in pregnancy and increasing viral meningitis, with fever, headache, and meningismus. The thereafter lead to ureteral dilatation and decreased peristalsis "rule of 7s" can help classifiz a patient at low risk of having that allow bacteria in the bladder to more easily ascend to the Lyme disease (headache duration <7 days, <7Oo/" mononuclear kidney, resulting in a much greater incidence of pyelonephri- cells in the cerebrospinal fluid [CSF], and absence of a seventh tis than that encountered in nonpregnant women. Cystitis facial nerve palsy). Lyme meningitis usually occurs in the and asymptomatic bacteriuria during pregnancy may also summer and fall in endemic areas (e.g., northeastern United be associated with low birth weight and preterm delivery States), and it is often associated with peripheral facial palsy. so treatment is indicated. Pending culture and susceptibility The patient works outdoors in an endemic state (Pennsylva- results, initiation of empiric antimicrobial therapy is indi- nia), and tick bite exposure is likely. cated. The recommended treatment duration for cystitis in Enteroviruses (Option A) are the most common cause pregnancy is generally 3 to 7 days. A single dose of fosfo of viral meningitis with symptoms including headache, mycin is a suitable but more costly alternative. Other than fever, nuchal rigidity, photophobia, nausea, vomiting, myal- in pregnant women, test of cure is not indicated in those gia, pharyngitis, maculopapular rash, and cough. Usually, a reporting symptom resolution. Follow-up urine cultures recently sick contact has been present (e.g., small children shortly after successful treatment completion are indicated in with viral illness). Facial palsy does not occur in enteroviral pregnant patients, with retreatment as needed. Controversy meningitis. exists regarding the beneflt of prophylactic antibiotic therapy

The most likely diagnosis is Borrelia burgdorferi meningitis Item 100 Answer: C (Option B). The flrst stage of Lyme disease usually presents Educational Objective: Treat cystitis during pregnancy. with a flu-like illness 7 to 4 weeks after infection. character- ized by an erythema migrans rash. Focal cardiac or neurologic Cystitis in a pregnant woman is considered a complicated symptoms may also occur in early disseminated disease, typ- urinary tract infection and requires a urine culture and ically 2 to 10 weeks following the development of the rash. prompt treatment with antibiotics; cefpodoxime proxetil is Although Lyme meningitis can involve any cranial nerve, an acceptable and safe choice in pregnant women (Option facial nerve palsy is the most common manifestation, occur- C), as are other cephalosporin agents (cephalexin, cefdinir) ring in B'2, of patients with Lyme disease. I-yme disease causes and amoxicillin-clavulanate. Physiologic alterations in the a lymphocytic meningitis that may be indistinguishable from urinary tract beginning early in pregnancy and increasing viral meningitis, with fever, headache, and meningismus. The thereafter lead to ureteral dilatation and decreased peristalsis "rule of 7s" can help classifiz a patient at low risk of having that allow bacteria in the bladder to more easily ascend to the Lyme disease (headache duration <7 days, <7Oo/" mononuclear kidney, resulting in a much greater incidence of pyelonephri- cells in the cerebrospinal fluid [CSF], and absence of a seventh tis than that encountered in nonpregnant women. Cystitis facial nerve palsy). Lyme meningitis usually occurs in the and asymptomatic bacteriuria during pregnancy may also summer and fall in endemic areas (e.g., northeastern United be associated with low birth weight and preterm delivery States), and it is often associated with peripheral facial palsy. so treatment is indicated. Pending culture and susceptibility The patient works outdoors in an endemic state (Pennsylva- results, initiation of empiric antimicrobial therapy is indi- nia), and tick bite exposure is likely. cated. The recommended treatment duration for cystitis in Enteroviruses (Option A) are the most common cause pregnancy is generally 3 to 7 days. A single dose of fosfo of viral meningitis with symptoms including headache, mycin is a suitable but more costly alternative. Other than fever, nuchal rigidity, photophobia, nausea, vomiting, myal- in pregnant women, test of cure is not indicated in those gia, pharyngitis, maculopapular rash, and cough. Usually, a reporting symptom resolution. Follow-up urine cultures recently sick contact has been present (e.g., small children shortly after successful treatment completion are indicated in with viral illness). Facial palsy does not occur in enteroviral pregnant patients, with retreatment as needed. Controversy meningitis. exists regarding the beneflt of prophylactic antibiotic therapy 189

Answers and Critiques rate' and her high fever, increased heart rate and respiration throughout the remainder of pregnancy in women who have hypotension are also signs of sepsis' Although not usually recurrent infections. tuberculosis can (Option in itre differential diagnosis, disseminated Case control studies associate nitrofurantoin if not diagnosed and in induce classic septic shock and death A) with birth defects. These flndings were not duplicated treated PromPtlY and adequatelY' a prospective study of women treated with nitrofurantoin Sepsis, pancytopenia, oral ulcerations' and hepato- for asymptomatic bacteriuria. A reasonable approach is to are typi- splenomegaly in an immunosuppressed patient avoid nitrofurantoin in the flrst trimester if a safer antibiotic (Option A)' However' cal of disseminated histoplasmosis choice is available. Because trimethoprim is a folic acid antagonist, its use the Histoplasmaserum and urinary antigen were negative; 80% these tests have a sensitivity and specificity approaching is avoided in the flrst trimester for fear of causing neu- ral tube defects. Sulfonamides are avoided before delivery in immunosuppressed patients with disseminated infection' because they can displace bilirubin from plasma binding making this diagnosis less likely. sites in the newborn and theoretically cause kernicterus' The triad of pneumococcal endocarditis, meningitis' D J Trimethoprim-sulfamethoxazole (Option B) can be given and pneumonia (Austrian syndrome) is the result of Strepto- UI E safely during the second trimester. coccus pneumonioebacteremia (Option C)' However, this is o an acute and rapidly progressive disease and is not compat- Il t/t Because fluoroquinolones have demonstrated toxicity o, to developing cartilage in experimental animal studies, they ible with this patient's 6 week course of progressive illness' - EL are generally avoided during pregnancy and lactation. These Repetitive inhalation of antigens in a sensitized patient rr -l flndings have not been documented in humans, but for can result in hypersensitivity pneumonitis (HP) (Option D)' ar,. the sake of safety, fluoroquinolones (Option D) are avoided Patients with subacute HP have a chronic low-level exposure ll to antigens and experience cough, fatigue, weight loss, and E during pregnancy and lactation if a safer alternative antibi .D an otic is available. shortness of breath. High-resolution CT will show micro- nodules and ground-glass opacities. Subacute HP does not I(EY POINTS involve the bone marrow or liver or result in sepsis. . Cystitis in pregnant women is considered a complicated KEY POIT{TS urinary tract infection and requires a urine culture and prompt treatment with antibiotics such as cefpo- o Immunosuppression is a risk factor for disseminated doxime proxetil, cephalexin, cefdinir, and amoxicillin tuberculosis, which often involves the lungs, liver, and clavulanate. bone marrow and may result in systemic inflammatory . Follow-up urine cultures after treatment of urinary response syndrome, septic shock, and death.

rate' and her high fever, increased heart rate and respiration throughout the remainder of pregnancy in women who have hypotension are also signs of sepsis' Although not usually recurrent infections. tuberculosis can (Option in itre differential diagnosis, disseminated Case control studies associate nitrofurantoin if not diagnosed and in induce classic septic shock and death A) with birth defects. These flndings were not duplicated treated PromPtlY and adequatelY' a prospective study of women treated with nitrofurantoin Sepsis, pancytopenia, oral ulcerations' and hepato- for asymptomatic bacteriuria. A reasonable approach is to are typi- splenomegaly in an immunosuppressed patient avoid nitrofurantoin in the flrst trimester if a safer antibiotic (Option A)' However' cal of disseminated histoplasmosis choice is available. Because trimethoprim is a folic acid antagonist, its use the Histoplasmaserum and urinary antigen were negative; 80% these tests have a sensitivity and specificity approaching is avoided in the flrst trimester for fear of causing neu- ral tube defects. Sulfonamides are avoided before delivery in immunosuppressed patients with disseminated infection' because they can displace bilirubin from plasma binding making this diagnosis less likely. sites in the newborn and theoretically cause kernicterus' The triad of pneumococcal endocarditis, meningitis' D J Trimethoprim-sulfamethoxazole (Option B) can be given and pneumonia (Austrian syndrome) is the result of Strepto- UI E safely during the second trimester. coccus pneumonioebacteremia (Option C)' However, this is o an acute and rapidly progressive disease and is not compat- Il t/t Because fluoroquinolones have demonstrated toxicity o, to developing cartilage in experimental animal studies, they ible with this patient's 6 week course of progressive illness' - EL are generally avoided during pregnancy and lactation. These Repetitive inhalation of antigens in a sensitized patient rr -l flndings have not been documented in humans, but for can result in hypersensitivity pneumonitis (HP) (Option D)' ar,. the sake of safety, fluoroquinolones (Option D) are avoided Patients with subacute HP have a chronic low-level exposure ll to antigens and experience cough, fatigue, weight loss, and E during pregnancy and lactation if a safer alternative antibi .D an otic is available. shortness of breath. High-resolution CT will show micro- nodules and ground-glass opacities. Subacute HP does not I(EY POINTS involve the bone marrow or liver or result in sepsis. . Cystitis in pregnant women is considered a complicated KEY POIT{TS urinary tract infection and requires a urine culture and prompt treatment with antibiotics such as cefpo- o Immunosuppression is a risk factor for disseminated doxime proxetil, cephalexin, cefdinir, and amoxicillin tuberculosis, which often involves the lungs, liver, and clavulanate. bone marrow and may result in systemic inflammatory . Follow-up urine cultures after treatment of urinary response syndrome, septic shock, and death. tract infections are indicated in pregnant patients. . The interferon-y release assay may be negative in patients with disseminated tuberculosis. Bibliography Abou Heidar NF, Degheili JA. Yacoubian AA, et al. Management of urinary Bibliography tract infection in women: A practical approach for everyday practice. Sharma SK, Mohan A. Miliary Tuberculosis. Microbiol Spectr. 2017;5(2):10. Urol Ann. 2019 Oct-Dec:11:339 346. [PMID: YOqSqsOl doi:10.4103/ 112B/microbiolspec.TNMIT-0013-2016. Ipttltn, 282814411 doi:10.1128 / uA.uA to4-t9 microbiolspec.TNMIT 0013-2016

tract infections are indicated in pregnant patients. . The interferon-y release assay may be negative in patients with disseminated tuberculosis. Bibliography Abou Heidar NF, Degheili JA. Yacoubian AA, et al. Management of urinary Bibliography tract infection in women: A practical approach for everyday practice. Sharma SK, Mohan A. Miliary Tuberculosis. Microbiol Spectr. 2017;5(2):10. Urol Ann. 2019 Oct-Dec:11:339 346. [PMID: YOqSqsOl doi:10.4103/ 112B/microbiolspec.TNMIT-0013-2016. Ipttltn, 282814411 doi:10.1128 / uA.uA to4-t9 microbiolspec.TNMIT 0013-2016 Item 101 Answer: B Item 102 Answer: B Ed u cati o n a I O bi ective : Diagnose disseminated Educational Objective: Prevent HIV infection in persons tuberculosis infection. with sexual risk factors. The most likely diagnosis is disseminated tuberculosis infection The most appropriate additional management for this patient (Option B). This patient's use of a biologic immune modi- is pre-exposure prophylaxis (PrEP) with daily tenofovir- fier (ustekinumab) is a signiflcant risk factor for tuberculo- emtricitabine (Option B). He has several risk factors for HIV sis reactivation or dissemination. The patient's interferon-y acquisition, including diagnoses of rectal gonorrhea and release assay was negative, but anergz is observed more fre- syphilis, history of condomless sex, and insertive and recep- quently among patients with miliary tuberculosis than those tive anal sex. PrEP is recommended for populations in which with pulmonary or isolated extrapulmonary involvement. annual HIV incidence is at least 2'2,, which applies to menwho Disseminated tuberculosis often involves the lungs, liver, and have sex with men (MSM) in the United States, especiallywith bone marrow. The patient's chest radiograph reveals the bilat- risk factors previously described. With good adherence, the eral presence of innumerable 1 to 3-mm nodules. These efficacy of daily PrEP in MSM can be as high as 92%. A fourth findings, although not specific, are typical of tuberculosis generation HIV antigen/antibody combination assay should dissemination through the vasculature or the lymphatic ves be performed within 7 days of PrEP initiation and repeated sels. She also has pancytopenia, an indication of bone mar- every 3 months; additionally, sexually transmitted infection row involvement, and increased alkaline phosphatase and screening should be done every 3 months, and serum cre- aminotransferase levels indicate hepatic involvement. Finally, atinine should be evaluated every 6 months. Since 2OI2, the

Item 101 Answer: B Item 102 Answer: B Ed u cati o n a I O bi ective : Diagnose disseminated Educational Objective: Prevent HIV infection in persons tuberculosis infection. with sexual risk factors. The most likely diagnosis is disseminated tuberculosis infection The most appropriate additional management for this patient (Option B). This patient's use of a biologic immune modi- is pre-exposure prophylaxis (PrEP) with daily tenofovir- fier (ustekinumab) is a signiflcant risk factor for tuberculo- emtricitabine (Option B). He has several risk factors for HIV sis reactivation or dissemination. The patient's interferon-y acquisition, including diagnoses of rectal gonorrhea and release assay was negative, but anergz is observed more fre- syphilis, history of condomless sex, and insertive and recep- quently among patients with miliary tuberculosis than those tive anal sex. PrEP is recommended for populations in which with pulmonary or isolated extrapulmonary involvement. annual HIV incidence is at least 2'2,, which applies to menwho Disseminated tuberculosis often involves the lungs, liver, and have sex with men (MSM) in the United States, especiallywith bone marrow. The patient's chest radiograph reveals the bilat- risk factors previously described. With good adherence, the eral presence of innumerable 1 to 3-mm nodules. These efficacy of daily PrEP in MSM can be as high as 92%. A fourth findings, although not specific, are typical of tuberculosis generation HIV antigen/antibody combination assay should dissemination through the vasculature or the lymphatic ves be performed within 7 days of PrEP initiation and repeated sels. She also has pancytopenia, an indication of bone mar- every 3 months; additionally, sexually transmitted infection row involvement, and increased alkaline phosphatase and screening should be done every 3 months, and serum cre- aminotransferase levels indicate hepatic involvement. Finally, atinine should be evaluated every 6 months. Since 2OI2, the 190

Answers and Critiques coformulation of tenofovir disoproxil fumarate (TDF) and fbbrile disease; however. alterations in parasympathetic auto emtricitabine has been used for prevention and has been nomic f'unction comnionly occur. Mer-rtation is not altered. found to be safe overall, aside from a low risk of kidney dys- No specific diagnostic laboratory abnornralities are associated function and reduced bone mineral density. Because of this, with botulism. Imaging studies help exclude other treurologic TDF and emtricitabine is not recommended for persons with entities. Confirmation relies on detecting toxin ir-r fbods. gas a creatinine clearance less than 60 ml/min, and dual-ener$/ tric secretions, stool, or semm. Supportive care and prompt x-ray absorptiometry scanning is recommended in men older udministration of' heptavalent botulinum antitoxin are the than 50 years and others at risk for osteoporosis. A second mainstays of management. Botulisrn can also be acquired by PrEP regimen, daily tenofovir alafenamide (TAF) and emtri inl-ralation of purified toxin deliberately teleased in the air. citabine, with a presumed lower risk of kidney and bone- Acute flaccid myelitis (Option A) is a newly describecl related adverse effects, was approved in 2019 for use in men at paralytic neurologic disease linked to respiratory infections high risk of HIV infection. ir-rvolving neuroinvasive enteroviruses. It presents with the Tenofovir and emtricitabine-based regimens have been arcute onset of arm or leg weakness and loss of'reflexes. ta o shown to have higher efficacy than tenofovir alone for PrEP; Other manif'estations include facial, ocular. and oropharyn J ET neither TDF nor TAF monotherapy is recommended as PrEP geal muscle rneakness. a- P .I

coformulation of tenofovir disoproxil fumarate (TDF) and fbbrile disease; however. alterations in parasympathetic auto emtricitabine has been used for prevention and has been nomic f'unction comnionly occur. Mer-rtation is not altered. found to be safe overall, aside from a low risk of kidney dys- No specific diagnostic laboratory abnornralities are associated function and reduced bone mineral density. Because of this, with botulism. Imaging studies help exclude other treurologic TDF and emtricitabine is not recommended for persons with entities. Confirmation relies on detecting toxin ir-r fbods. gas a creatinine clearance less than 60 ml/min, and dual-ener$/ tric secretions, stool, or semm. Supportive care and prompt x-ray absorptiometry scanning is recommended in men older udministration of' heptavalent botulinum antitoxin are the than 50 years and others at risk for osteoporosis. A second mainstays of management. Botulisrn can also be acquired by PrEP regimen, daily tenofovir alafenamide (TAF) and emtri inl-ralation of purified toxin deliberately teleased in the air. citabine, with a presumed lower risk of kidney and bone- Acute flaccid myelitis (Option A) is a newly describecl related adverse effects, was approved in 2019 for use in men at paralytic neurologic disease linked to respiratory infections high risk of HIV infection. ir-rvolving neuroinvasive enteroviruses. It presents with the Tenofovir and emtricitabine-based regimens have been arcute onset of arm or leg weakness and loss of'reflexes. ta o shown to have higher efficacy than tenofovir alone for PrEP; Other manif'estations include facial, ocular. and oropharyn J ET neither TDF nor TAF monotherapy is recommended as PrEP geal muscle rneakness. a- P .I therapy (Option A). Guillain-Barre syndronre (Option C) is an acute inflam L' L

therapy (Option A). Guillain-Barre syndronre (Option C) is an acute inflam L' L The combination of tenofovir emtricitabine, plus either nratory polyneuropathy ofter-r precedecl by a respiratory or Es raltegravir or dolutegravir is an HIV postexposure prophy- grstrointestinal inf'ection, most often Campylobncter. It is ag laxis regimen to be given following a high-risk exposure considered an autoirnmune process triggered by the inf'ec tt L (Option C). It could also be considered in a patient with tious agent. Lower extremity proximal muscle weakness o UI newly diagnosed HIV. Neither of these conditions applies to and areflexia. ascending to involve the arms and trunk, is = E this patient. the typical early presentation. Cranial nerve dysfunction Counseling on condom use and frequent HIV and STI r-rsually does not become prominent until later in the course screening alone is not enough in high-risk groups (Option ol disease. D). Several studies have shown that expanded screening for Paralytic shellfish poisoning (Option D) is associatecl HIV and expansion of PrEP in persons at high risk who are with the consumption of bivalve mollusks (clams, mussels) HIV negative are key factors in curbing and ending the HIV thirt have accumulated saxitoxin, produced by algae. Synip epidemic in the United States. toms usually commence within minutes to I hour after ingestion, manifesting with circumoral and extremity pares I(EY POITT thesias. Cranial nerve involvement and muscle weakness are o Pre-exposure prophylaxis with tenofovir disoproxil variable. Gastrointestinal symptoms may occur. fumarate and emtricitabine is recommended in all The early appearance of cranial nerve findings and lack populations with an annual HIV incidence greater of sensory symptonrs make botulism more likely than acute than2%, including in men who have sex with men. flaccid myelitis, Guillain-Barre syndrome. and paralytic shellfisl-r poisoning. Bibliography KEY POIT{T Centers for Disease Control and Prevention. Preexposure prophylaxis fbr the prevention of HIV infbction in the United States - 2017 Update. A clinical o In patients with botulism, cranial nerve defects and practice guideline. Available at: https://www.cdc.gov/hiv/pdf/risk/prep/ cdc-hiv-prep-guidelines 2017.pdf. bulbar signs (the 4 Ds: diplopia, dysphonia, dysarthria, and dysphagia) appear first, followed by weakness and flaccid paralysis in the upper extremities, descending to the trunk and lower limbs. tr Item 103 Answer: B Educational Objective: Diagnose botulism. Bibliography lhis man's signs ar-rd symptoms are cc.rnsistent with botulisrn Adalja AA, Toner E, Inglesby TV. Clinical management of potential bioterror- ism-related conditions. N EnglJ Med. 2015;372:954 62. [ptr,ltp, zszza,zl (Option B), r,l,hich was likely acquired from ingesting bot doi:10. 1056/NElMral409755 ulinum toxin-contanrinatecl fbod during his cruise. Cranial nerue clef'ects and bulbar signs (the + Ds: diplopia, dyspl"ro nia. dysarlhria, and dysphagia) appear approximately 12 to Item 104 Answer: C 116 hours after toxin ingestion. fbllowed by weakness and f lac Ed ucationa I Objective: Prevent opportunistic infection cid paralysis in the upper extremities, clescending to the trunk in a patient with AIDS. and lower limbs. Obstructive upper airway issues ancl dia phragmatic rteakness can lead to respiratory- failure requiriug The most appropriate additional treatment is antimicrobial mechanic:il ver-rtilation. Deep tendon reflexes can becorne prophylaxis with trimethoprim-sulfamethoxazole (Option diminished, but sensation remains intact. Constipation is C). This patient has advanced HIV with a CD4 cell count of the most common gastrointestinal manifestation but tlav 45l1tL, which is classifled as AIDS (AIDS diagnostic criteria be preceded by nausea and rnild diarrhea. Botulism is not it include either the presence of an AlDS-deflning condition

The combination of tenofovir emtricitabine, plus either nratory polyneuropathy ofter-r precedecl by a respiratory or Es raltegravir or dolutegravir is an HIV postexposure prophy- grstrointestinal inf'ection, most often Campylobncter. It is ag laxis regimen to be given following a high-risk exposure considered an autoirnmune process triggered by the inf'ec tt L (Option C). It could also be considered in a patient with tious agent. Lower extremity proximal muscle weakness o UI newly diagnosed HIV. Neither of these conditions applies to and areflexia. ascending to involve the arms and trunk, is = E this patient. the typical early presentation. Cranial nerve dysfunction Counseling on condom use and frequent HIV and STI r-rsually does not become prominent until later in the course screening alone is not enough in high-risk groups (Option ol disease. D). Several studies have shown that expanded screening for Paralytic shellfish poisoning (Option D) is associatecl HIV and expansion of PrEP in persons at high risk who are with the consumption of bivalve mollusks (clams, mussels) HIV negative are key factors in curbing and ending the HIV thirt have accumulated saxitoxin, produced by algae. Synip epidemic in the United States. toms usually commence within minutes to I hour after ingestion, manifesting with circumoral and extremity pares I(EY POITT thesias. Cranial nerve involvement and muscle weakness are o Pre-exposure prophylaxis with tenofovir disoproxil variable. Gastrointestinal symptoms may occur. fumarate and emtricitabine is recommended in all The early appearance of cranial nerve findings and lack populations with an annual HIV incidence greater of sensory symptonrs make botulism more likely than acute than2%, including in men who have sex with men. flaccid myelitis, Guillain-Barre syndrome. and paralytic shellfisl-r poisoning. Bibliography KEY POIT{T Centers for Disease Control and Prevention. Preexposure prophylaxis fbr the prevention of HIV infbction in the United States - 2017 Update. A clinical o In patients with botulism, cranial nerve defects and practice guideline. Available at: https://www.cdc.gov/hiv/pdf/risk/prep/ cdc-hiv-prep-guidelines 2017.pdf. bulbar signs (the 4 Ds: diplopia, dysphonia, dysarthria, and dysphagia) appear first, followed by weakness and flaccid paralysis in the upper extremities, descending to the trunk and lower limbs. tr Item 103 Answer: B Educational Objective: Diagnose botulism. Bibliography lhis man's signs ar-rd symptoms are cc.rnsistent with botulisrn Adalja AA, Toner E, Inglesby TV. Clinical management of potential bioterror- ism-related conditions. N EnglJ Med. 2015;372:954 62. [ptr,ltp, zszza,zl (Option B), r,l,hich was likely acquired from ingesting bot doi:10. 1056/NElMral409755 ulinum toxin-contanrinatecl fbod during his cruise. Cranial nerue clef'ects and bulbar signs (the + Ds: diplopia, dyspl"ro nia. dysarlhria, and dysphagia) appear approximately 12 to Item 104 Answer: C 116 hours after toxin ingestion. fbllowed by weakness and f lac Ed ucationa I Objective: Prevent opportunistic infection cid paralysis in the upper extremities, clescending to the trunk in a patient with AIDS. and lower limbs. Obstructive upper airway issues ancl dia phragmatic rteakness can lead to respiratory- failure requiriug The most appropriate additional treatment is antimicrobial mechanic:il ver-rtilation. Deep tendon reflexes can becorne prophylaxis with trimethoprim-sulfamethoxazole (Option diminished, but sensation remains intact. Constipation is C). This patient has advanced HIV with a CD4 cell count of the most common gastrointestinal manifestation but tlav 45l1tL, which is classifled as AIDS (AIDS diagnostic criteria be preceded by nausea and rnild diarrhea. Botulism is not it include either the presence of an AlDS-deflning condition 191

Answers and Critiques or a CD4 cell count <200 cells/pl). His risk for Pneumocys- Item 105 Answer: E tis jirouecii pneumonia is high, and he would beneflt from Ed ucationa I Objective: Prevent travelers' diarrhea. Pneumocystis prophylaxis. Starting immediate antiretroviral therapy (ART) will address his immunosuppression; a high This patient should be prescribed daily antibiotic prophylaxis viral load is one of the key factors that influences the inci- with rifaximin (Option E). Travelers' diarrhea is the most dence of opportunistic infections in advanced HIV infection. frequently acquired infectious illness encountered by inter- However, guidelines recommen d Pneumocystis prophylaxis national travelers. It is generally mild to severe, with variable initiation concomitant with ARI initiation. Treatment with symptoms from loose stools and cramps to bloody dysen trimethoprim-sulfamethoxazole will also provide protection tery and systemic illness. Most cases occur in the initial few against toxoplasmosis in patients with positive serologz and weeks and decrease thereafter. Enterotoxigenic Escherichia CD4 cell count less than 100/pL. coli, Campylobacter, Shigella, and So I mo nella are estimated Previously, prophylaxi s for My co b acterium au ium com - to account for 80% to 90% of infecting organisms. \'iruses D plex (MAC) with weekly azithromycin was recommended in (e.g., rotavirus, norovirus) and, to a lesser extent, protozoal J (a patients with CD4 cell counts less than 50/prl (Option A). parasites (e.9., Giardia, Cyclospora) are mostly responsible € (D However, newer evidence suggests the risk for MAC is low for the remainder. Most illness resolves within 3 to 7 days - UI among these patients taking ARL Therefore, primary MAC even without therapy, although those involving parasites can o, prophylaxis is no longer recommended in newly diagnosed persist for longer periods of time. Daily prophylactic antibi J CL patients prescribed ART. otics are eflective at reducing the rate of diarrhea, but risks of ..t *- Mucosal Candida infections like oropharyngeal candi- adverse effects and increasing antimicrobial resistance must -a diasis have very low morbidity and mortality and respond be considered before prescribing. In patients with underlying It -a conditions that place them at higher risk of infection or dis- L well to azole therapy. Concern exists that primary flucon- .D ul azole prophylaxis could lead to development of azole- ease complications (e.g., immune compromise, inflammatory resistant Candida strains, so primary prophylaxis for bowel disease, chronic kidney disease) their use should be Candida infections or other fungal infections is not recom- considered. This patient has ulcerative colitis, which increases mended (Option B). her risk for travelers' diarrhea becoming severe and disruptive Offering no additional therapy would be inappropriate to travel; prophylaxis with rifaximin should be considered for in this patient with a very low CD4 cell count and high risk this patient. for infection (Option D). Guidelines suggest that Pneumo- Bismuth subsalicylate (Option A) taken in multiple cystis prophylaxis be continued until the CD4 cell count daily doses can help prevent diarrhea but is not as conven responds to ongoing ART, increases to more than 200/pL, and ient as rifaximin and carries the risk of salicylate toxicity. stays above 2OOlltL for more than 3 months. Some studies Fluoroquinolones (such as ciprofloxacin) (Option B) are have shown that Pneumocystis infection risk decreases dra- not recommended for prophylaxis in patients at increased risk matically when patients achieve virologic suppression despite because of increasing safety concerns and bacterial resistance. the CD4 cell count being less than 2OOl1tL, so guidelines Preventive measures include careful food and water suggest that primary prophylaxis for Pneumocgstis could selection, water puriflcation methods, and prophylactic be stopped in patients with CD4 cell counts above 100/pL nonantimicrobial and antimicrobial agents. Unopened bot- if consistent virologic suppression continues for more than tled water should be used for drinking and dental care in 3 months. areas where concerns about contaminated tap water exist. Water may also be purifled by boiling or adding sodium t(EY P0tlrTS hypochlorite or iodine. Compact commercial water fllters o Patients with advanced HIV infection and CD4 cell (Option C) have not been proven effective and should not be counts less than 2OOlltL should start prophylaxis for relied on as a safe method of disinfecting water. Pneumocy stis j irou ecii. Randomized clinical trials studying the beneflts of o Primary prophylaxis for Pneumocgstis in patients probiotics (Option D) in preventing travelers' diarrhea are with HIV can be discontinued when the CD4 cell lacking; therefore, they cannot be recommended. count exceeds 2OOlltL for at least 3 months or if IEY POIf{TS the CD4 cell count exceeds 100/pL and consistent virologic suppression continues for more than o Travelers' diarrhea prophylaxis with rifaximin is rec- 3 months. ommended in patients with underlying conditions that place them at higher risk of infection or disease Bibliography complications (e.g., immune compromise, inflamma Panel on Opportunistic Infections in HlV-lnfected Adults and Adolescents. tory bowel disease, chronic kidney disease). Guidelines for the prevention and treatment of opportunistic infections in HlV-infected adults and adolescents: recommendations fiom the Centers . Fluoroquinolones are not recommended for travelers' for Disease Control and Prevention, the National Institutes of Health. and diarrhea prophylaxis in patients at increased risk the HIV Medicine Association of the Infectious Diseases Society of America. Updated February 11, 2O2O. Available at https:r'aidsinfo. because of increasing safety concerns and bacterial nih.gov/guidelines/htmli 4/adult-and adolescent-opportunistic- resistance. infection/0

or a CD4 cell count <200 cells/pl). His risk for Pneumocys- Item 105 Answer: E tis jirouecii pneumonia is high, and he would beneflt from Ed ucationa I Objective: Prevent travelers' diarrhea. Pneumocystis prophylaxis. Starting immediate antiretroviral therapy (ART) will address his immunosuppression; a high This patient should be prescribed daily antibiotic prophylaxis viral load is one of the key factors that influences the inci- with rifaximin (Option E). Travelers' diarrhea is the most dence of opportunistic infections in advanced HIV infection. frequently acquired infectious illness encountered by inter- However, guidelines recommen d Pneumocystis prophylaxis national travelers. It is generally mild to severe, with variable initiation concomitant with ARI initiation. Treatment with symptoms from loose stools and cramps to bloody dysen trimethoprim-sulfamethoxazole will also provide protection tery and systemic illness. Most cases occur in the initial few against toxoplasmosis in patients with positive serologz and weeks and decrease thereafter. Enterotoxigenic Escherichia CD4 cell count less than 100/pL. coli, Campylobacter, Shigella, and So I mo nella are estimated Previously, prophylaxi s for My co b acterium au ium com - to account for 80% to 90% of infecting organisms. \'iruses D plex (MAC) with weekly azithromycin was recommended in (e.g., rotavirus, norovirus) and, to a lesser extent, protozoal J (a patients with CD4 cell counts less than 50/prl (Option A). parasites (e.9., Giardia, Cyclospora) are mostly responsible € (D However, newer evidence suggests the risk for MAC is low for the remainder. Most illness resolves within 3 to 7 days - UI among these patients taking ARL Therefore, primary MAC even without therapy, although those involving parasites can o, prophylaxis is no longer recommended in newly diagnosed persist for longer periods of time. Daily prophylactic antibi J CL patients prescribed ART. otics are eflective at reducing the rate of diarrhea, but risks of ..t *- Mucosal Candida infections like oropharyngeal candi- adverse effects and increasing antimicrobial resistance must -a diasis have very low morbidity and mortality and respond be considered before prescribing. In patients with underlying It -a conditions that place them at higher risk of infection or dis- L well to azole therapy. Concern exists that primary flucon- .D ul azole prophylaxis could lead to development of azole- ease complications (e.g., immune compromise, inflammatory resistant Candida strains, so primary prophylaxis for bowel disease, chronic kidney disease) their use should be Candida infections or other fungal infections is not recom- considered. This patient has ulcerative colitis, which increases mended (Option B). her risk for travelers' diarrhea becoming severe and disruptive Offering no additional therapy would be inappropriate to travel; prophylaxis with rifaximin should be considered for in this patient with a very low CD4 cell count and high risk this patient. for infection (Option D). Guidelines suggest that Pneumo- Bismuth subsalicylate (Option A) taken in multiple cystis prophylaxis be continued until the CD4 cell count daily doses can help prevent diarrhea but is not as conven responds to ongoing ART, increases to more than 200/pL, and ient as rifaximin and carries the risk of salicylate toxicity. stays above 2OOlltL for more than 3 months. Some studies Fluoroquinolones (such as ciprofloxacin) (Option B) are have shown that Pneumocystis infection risk decreases dra- not recommended for prophylaxis in patients at increased risk matically when patients achieve virologic suppression despite because of increasing safety concerns and bacterial resistance. the CD4 cell count being less than 2OOl1tL, so guidelines Preventive measures include careful food and water suggest that primary prophylaxis for Pneumocgstis could selection, water puriflcation methods, and prophylactic be stopped in patients with CD4 cell counts above 100/pL nonantimicrobial and antimicrobial agents. Unopened bot- if consistent virologic suppression continues for more than tled water should be used for drinking and dental care in 3 months. areas where concerns about contaminated tap water exist. Water may also be purifled by boiling or adding sodium t(EY P0tlrTS hypochlorite or iodine. Compact commercial water fllters o Patients with advanced HIV infection and CD4 cell (Option C) have not been proven effective and should not be counts less than 2OOlltL should start prophylaxis for relied on as a safe method of disinfecting water. Pneumocy stis j irou ecii. Randomized clinical trials studying the beneflts of o Primary prophylaxis for Pneumocgstis in patients probiotics (Option D) in preventing travelers' diarrhea are with HIV can be discontinued when the CD4 cell lacking; therefore, they cannot be recommended. count exceeds 2OOlltL for at least 3 months or if IEY POIf{TS the CD4 cell count exceeds 100/pL and consistent virologic suppression continues for more than o Travelers' diarrhea prophylaxis with rifaximin is rec- 3 months. ommended in patients with underlying conditions that place them at higher risk of infection or disease Bibliography complications (e.g., immune compromise, inflamma Panel on Opportunistic Infections in HlV-lnfected Adults and Adolescents. tory bowel disease, chronic kidney disease). Guidelines for the prevention and treatment of opportunistic infections in HlV-infected adults and adolescents: recommendations fiom the Centers . Fluoroquinolones are not recommended for travelers' for Disease Control and Prevention, the National Institutes of Health. and diarrhea prophylaxis in patients at increased risk the HIV Medicine Association of the Infectious Diseases Society of America. Updated February 11, 2O2O. Available at https:r'aidsinfo. because of increasing safety concerns and bacterial nih.gov/guidelines/htmli 4/adult-and adolescent-opportunistic- resistance. infection/0 192

Answers and Critiques Bibliography Bibliography Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and Wright WE Pinto CN, Palisoc K, et al. Viral (aseptic) meningitis: A review J treatment of travelers'-diarrhea: a graded expert panel ieport. J Travel Neurol Sci. 2Ol9;398:176-183. [PMID: 30731305] doi:10.1016/j.jns.2019.01.050 Med. 2017 ;24: SS7- S74. [p]r,ttO, 28S210041 doi: 10. 10t3 /jtm/tix026

Bibliography Bibliography Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and Wright WE Pinto CN, Palisoc K, et al. Viral (aseptic) meningitis: A review J treatment of travelers'-diarrhea: a graded expert panel ieport. J Travel Neurol Sci. 2Ol9;398:176-183. [PMID: 30731305] doi:10.1016/j.jns.2019.01.050 Med. 2017 ;24: SS7- S74. [p]r,ttO, 28S210041 doi: 10. 10t3 /jtm/tix026 Item 107 Answer: B tr Item 106 Answer: A Educationa I Objective: Diegnose entenovirus meningitis. Ed ucati ona I O bjective : Treat hospital -acquired pneumonia. tr Enteroviruses (Option A) are one of the most comnlon causes The most appropritte treirtment is switching fronr cef'epirne of aseptic meningitis occurring in the summer ancl fall. Myal to cefazolin (Option B). 'lhis patient has hospital acquired gia. sore throat, maculopapular rash. and cough are corrmon pneumonia (HAP) caused by methicillin sensitive Sfaphyb- synrptoms in addition to typical meningitis syll.tptoms. Lym- cocrlrs oureus (MSSA), and antibiotic treatnrent fbr 7 days is phocytic pleocytosis of the cerebrospinal fluid (CSF) with lecolllnlended. HAP occurs 48 hours or nlore after admission a normal glucose level and mildly elevated protein level is and excludes infections incubating at the time of aclmis- vt (u typical. The diagnosis is confirmed by enterovirus polymerase sion (e.g.. Legbnella pneumonia has an incubation period J ET chain reaction (PCR) CSF testing. Treatment is supporlive, and of'2 l0 days). Empiric therapy regimens should be adjusted +. a- L the course is typically benign. based on culture. results, so cefepime should be changed to t Herpes simplex virus (HSV) type 1 (Option B) is the most cefazolin, which has a llarrower spectrum and good activity =, ? collrlon cause of sporadic viral encephalitis. These patier-rts against MSSA. Other treatnrent options are oxacillin and nat: G Ut may also present year round. The presence of abnormal brain cillin. Treatnrent for most patients with HAP is 7 days unless L q, functiorT distinguishes encephalitis from meningitis. Patients they have bacteremia, have a metastatic infection. show slow tl= with meningitis may be sick and uncomfbrtable, but brain response to ther:rpy. are inrmunocompromised, or have pyo- L

Item 107 Answer: B tr Item 106 Answer: A Educationa I Objective: Diegnose entenovirus meningitis. Ed ucati ona I O bjective : Treat hospital -acquired pneumonia. tr Enteroviruses (Option A) are one of the most comnlon causes The most appropritte treirtment is switching fronr cef'epirne of aseptic meningitis occurring in the summer ancl fall. Myal to cefazolin (Option B). 'lhis patient has hospital acquired gia. sore throat, maculopapular rash. and cough are corrmon pneumonia (HAP) caused by methicillin sensitive Sfaphyb- synrptoms in addition to typical meningitis syll.tptoms. Lym- cocrlrs oureus (MSSA), and antibiotic treatnrent fbr 7 days is phocytic pleocytosis of the cerebrospinal fluid (CSF) with lecolllnlended. HAP occurs 48 hours or nlore after admission a normal glucose level and mildly elevated protein level is and excludes infections incubating at the time of aclmis- vt (u typical. The diagnosis is confirmed by enterovirus polymerase sion (e.g.. Legbnella pneumonia has an incubation period J ET chain reaction (PCR) CSF testing. Treatment is supporlive, and of'2 l0 days). Empiric therapy regimens should be adjusted +. a- L the course is typically benign. based on culture. results, so cefepime should be changed to t Herpes simplex virus (HSV) type 1 (Option B) is the most cefazolin, which has a llarrower spectrum and good activity =, ? collrlon cause of sporadic viral encephalitis. These patier-rts against MSSA. Other treatnrent options are oxacillin and nat: G Ut may also present year round. The presence of abnormal brain cillin. Treatnrent for most patients with HAP is 7 days unless L q, functiorT distinguishes encephalitis from meningitis. Patients they have bacteremia, have a metastatic infection. show slow tl= with meningitis may be sick and uncomfbrtable, but brain response to ther:rpy. are inrmunocompromised, or have pyo- L function is normal. Patients with encephalitis may present genic complications (empyema. lung abscess), in which case with altered mental status, behavior and personality changes. a longer course of antibiotics may be warranted. hemiparesis, flaccid paralysis, paresthesias, or movement the approach to empiric therapy for HAP is similar to disorders. This patient does not have HSV-1 encephalitis. that fbr ventilator associated pneunronia. Patients should HSV-2 infbction (Option C) occurs year round. Patier-rts be assessed fbr risks tbr multidrug-resistant Pseudonlonos with HSV 2 meningitis have CSF findings similar to enterovi and other gram-negative bacilli and nrethicillin-resistant rus infection. HSV-2 meningitis is nclt associated with cough. S. oureus. ln the absence <;f' risk factors for multidrug- pharyngitis, or rash. However. many adults with primary resistant organisms or MRSA, guidelines recommend empiric HSV 2 meningitis have a history of genital lesions that precede treatment fbr HAP with piperacillin-tazoLractam. cefepime, the meningitis by about 7 days. The course of llSV-2 menin levofloxacin. imipenem, or nleropenenr. This patient did gitis in intmunocompetent patients is benign, and supporlive not have risk factors fbr multidrug-resistant organisms, so care is usually sufficient. Diagnosis is confirmed with CSF cet'epirle (Option A) as arr empiric agent was appropriate; PCR testing. hclwever. empiric regimens should be adjusted based on cul West Nile virus (Option D) is a mosquito-borne illness ture results to the most narnrw spectrum antibiotic appropri- that may present with a similar clinical and CSF profile to ate. Therefbre, continuing cefepime is no longer appropriate. other cxuses ol'viral meningitis and occurs between June and Cephalexin (Option C) is an appropriate oral antibiotic October. West Nile may present with meningitis, encephalitis. option fbr treating MSSA HAP. llowever. this patient does or a conrbinaticln of'the two, or as an isolated myelitis. lsolated not meet the criterirr to switch from intravenous to oral anti- rneningitis is nrore common in children. ln its nrost severe biotic therapy at this time. Criteria include stabilized vital firrm, inf'ection of'the anterior horn cells ciln cause a synl signs (heart rate <9O/ntin. respiration rate <20/mirt. stable metric or asymmetric flaccid parulysis, analogous to that seen bloocl pressure). temperature <38 "C (100.4 oF) for at least with polio. Patients with neuroinvasive disease rnay also have 24 h<lurs, resolving leukocvtosis (leukocyte count <15,000/pL a nuculopapular rash and a flu-like syndrome befbre neuro- [15 x lOelL]), and symptomatic improvement. logic disease onset, but it remains an uncomnlon cause of viral Piperacillin tazobactam (Option D) is overly broad cov' meningitis compared with enterovirus infbction. The diagnosis erage fbr MSSA HAP. It includes granl-negative ancl anlero- of West Nile neuroinvasive disease can be confirmed through bic activity, which is not needed. identification of'the IgM antibody in CSF or the serum. r(EY POtl{Tg t(EY P0rt{Ts . Broad-spectrum empiric anflbiotic therapy should always o Enterovirus meningitis commonly presents with be narrowed to a specific agent based on culture results. myalgia, sore throat, cough, and maculopapular rash, o Most patients with hospital-acquired pneumonia only in addition to typical meningitis symptoms. require treatment for 7 days; exceptions include o Many patients with primary herpes simplex virus patients who have bacteremia, have a metastatic type 2 meningitis have a history of genital lesions pre- infection, show slow response to therapy, are immu- ceding the onset of meningitis by about 7 days. nocompromised, or have pyogenic complications.

function is normal. Patients with encephalitis may present genic complications (empyema. lung abscess), in which case with altered mental status, behavior and personality changes. a longer course of antibiotics may be warranted. hemiparesis, flaccid paralysis, paresthesias, or movement the approach to empiric therapy for HAP is similar to disorders. This patient does not have HSV-1 encephalitis. that fbr ventilator associated pneunronia. Patients should HSV-2 infbction (Option C) occurs year round. Patier-rts be assessed fbr risks tbr multidrug-resistant Pseudonlonos with HSV 2 meningitis have CSF findings similar to enterovi and other gram-negative bacilli and nrethicillin-resistant rus infection. HSV-2 meningitis is nclt associated with cough. S. oureus. ln the absence <;f' risk factors for multidrug- pharyngitis, or rash. However. many adults with primary resistant organisms or MRSA, guidelines recommend empiric HSV 2 meningitis have a history of genital lesions that precede treatment fbr HAP with piperacillin-tazoLractam. cefepime, the meningitis by about 7 days. The course of llSV-2 menin levofloxacin. imipenem, or nleropenenr. This patient did gitis in intmunocompetent patients is benign, and supporlive not have risk factors fbr multidrug-resistant organisms, so care is usually sufficient. Diagnosis is confirmed with CSF cet'epirle (Option A) as arr empiric agent was appropriate; PCR testing. hclwever. empiric regimens should be adjusted based on cul West Nile virus (Option D) is a mosquito-borne illness ture results to the most narnrw spectrum antibiotic appropri- that may present with a similar clinical and CSF profile to ate. Therefbre, continuing cefepime is no longer appropriate. other cxuses ol'viral meningitis and occurs between June and Cephalexin (Option C) is an appropriate oral antibiotic October. West Nile may present with meningitis, encephalitis. option fbr treating MSSA HAP. llowever. this patient does or a conrbinaticln of'the two, or as an isolated myelitis. lsolated not meet the criterirr to switch from intravenous to oral anti- rneningitis is nrore common in children. ln its nrost severe biotic therapy at this time. Criteria include stabilized vital firrm, inf'ection of'the anterior horn cells ciln cause a synl signs (heart rate <9O/ntin. respiration rate <20/mirt. stable metric or asymmetric flaccid parulysis, analogous to that seen bloocl pressure). temperature <38 "C (100.4 oF) for at least with polio. Patients with neuroinvasive disease rnay also have 24 h<lurs, resolving leukocvtosis (leukocyte count <15,000/pL a nuculopapular rash and a flu-like syndrome befbre neuro- [15 x lOelL]), and symptomatic improvement. logic disease onset, but it remains an uncomnlon cause of viral Piperacillin tazobactam (Option D) is overly broad cov' meningitis compared with enterovirus infbction. The diagnosis erage fbr MSSA HAP. It includes granl-negative ancl anlero- of West Nile neuroinvasive disease can be confirmed through bic activity, which is not needed. identification of'the IgM antibody in CSF or the serum. r(EY POtl{Tg t(EY P0rt{Ts . Broad-spectrum empiric anflbiotic therapy should always o Enterovirus meningitis commonly presents with be narrowed to a specific agent based on culture results. myalgia, sore throat, cough, and maculopapular rash, o Most patients with hospital-acquired pneumonia only in addition to typical meningitis symptoms. require treatment for 7 days; exceptions include o Many patients with primary herpes simplex virus patients who have bacteremia, have a metastatic type 2 meningitis have a history of genital lesions pre- infection, show slow response to therapy, are immu- ceding the onset of meningitis by about 7 days. nocompromised, or have pyogenic complications. 193

Answers and Critiques Bibliography regimen is much less desirable than three weekly injections Kalit AC, Metersky ML, Klompas M, et al. Management of adults with hospital- of benzathine penicillin. acquired and ventilator associated pneumonia: 2016 clinical practice Long courses of therapy with doxycycline may be guidelines by the lnf'ectious Diseases Society of America and the American Thoracic Society. Clin Inf'ect Dis. 2016;63:e6l e111. [PMID, required to treat proctocolitis caused by the lymphogranu- '27418577 I doi: 10.1093/cid/ciw353 loma venereum (LGV) serovars (LL,L2, or L3) of Chlamydia trachomatis. LGV infections are increasing in the United States, and the NAAT for C. trachomatis would be positive in Item 108 Answer: B these cases. Patients usually present with more severe symp- Educational Obiective: Treat syphilis of unknown toms of proctocolitis and may have anal ulcers on examina- duration. tion. A course of doxycycline would be added to benzathine penicillin (Option C) if this patient did not respond to the Benzathine penicillin is the most appropriate treatment empiric therapy provided. D for this patient (Option B). Many laboratories use the The serologic results for this patient could be consistent J "reverse" serologic testing strategy for syphilis, starting with successfully treated syphilis because the speciflc test UI with an automated enzyme immunoassay (EIA) followed may remain positive indeflnitely. If the patient had reported = .D - by a nonspeciflc test (rapid plasma reagin [RPR] or Vene- UI a history of treatment for syphilis, then no further treatment o, real Disease Research Lab IVDRL] test). Patients with a would be necessaU (Option D). Patients with untreated syph J CL positive EIA result but negative RPR or VDRL test result ilis can also have a negative nonspecific test (RPR oTVDRL), so n - should have a second specific treponemal antibody test to anyone with two positive speciflc tests for syphilis, regardless t -a conflrm the result. Those with a confirmed positive result IO

Bibliography regimen is much less desirable than three weekly injections Kalit AC, Metersky ML, Klompas M, et al. Management of adults with hospital- of benzathine penicillin. acquired and ventilator associated pneumonia: 2016 clinical practice Long courses of therapy with doxycycline may be guidelines by the lnf'ectious Diseases Society of America and the American Thoracic Society. Clin Inf'ect Dis. 2016;63:e6l e111. [PMID, required to treat proctocolitis caused by the lymphogranu- '27418577 I doi: 10.1093/cid/ciw353 loma venereum (LGV) serovars (LL,L2, or L3) of Chlamydia trachomatis. LGV infections are increasing in the United States, and the NAAT for C. trachomatis would be positive in Item 108 Answer: B these cases. Patients usually present with more severe symp- Educational Obiective: Treat syphilis of unknown toms of proctocolitis and may have anal ulcers on examina- duration. tion. A course of doxycycline would be added to benzathine penicillin (Option C) if this patient did not respond to the Benzathine penicillin is the most appropriate treatment empiric therapy provided. D for this patient (Option B). Many laboratories use the The serologic results for this patient could be consistent J "reverse" serologic testing strategy for syphilis, starting with successfully treated syphilis because the speciflc test UI with an automated enzyme immunoassay (EIA) followed may remain positive indeflnitely. If the patient had reported = .D - by a nonspeciflc test (rapid plasma reagin [RPR] or Vene- UI a history of treatment for syphilis, then no further treatment o, real Disease Research Lab IVDRL] test). Patients with a would be necessaU (Option D). Patients with untreated syph J CL positive EIA result but negative RPR or VDRL test result ilis can also have a negative nonspecific test (RPR oTVDRL), so n - should have a second specific treponemal antibody test to anyone with two positive speciflc tests for syphilis, regardless t -a conflrm the result. Those with a confirmed positive result IO 4t of the nonspeciflc test result, and no history of treatment E and no history of syphilis treatment should be offered should be offered therapy for syphilis of unknown duration. .D UI treatment for syphilis of unknown duration with ben- zathine penicillin once weekly for three doses. In this t(tY P0ttT patient, nucleic acid ampliflcation testing (NAAT) con- o Without a history of previous syphilis treatment, flrmed a diagnosis of chlamydia proctitis, so the empiric patients with a positive specific test and confirmatory treatment provided with ceftriaxone and azithromycin specific test should be treated for syphilis of unknown would have been sufficient to treat that infection. duration with benzathine penicillin once weekly for Oral amoxicillin is not recommended to treat syphilis three doses. (Option A). In countries where benzathine penicillin was not available, observational studies have demonstrated suc- Bibliography cessful treatment of syphilis with long-duration, high dose Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J oral amoxicillin combined with probenecid. This long oral Med. 2020:382:845-854. [PMID: gZtOtOOOI doi:10.1056iNEJMra1901593

4t of the nonspeciflc test result, and no history of treatment E and no history of syphilis treatment should be offered should be offered therapy for syphilis of unknown duration. .D UI treatment for syphilis of unknown duration with ben- zathine penicillin once weekly for three doses. In this t(tY P0ttT patient, nucleic acid ampliflcation testing (NAAT) con- o Without a history of previous syphilis treatment, flrmed a diagnosis of chlamydia proctitis, so the empiric patients with a positive specific test and confirmatory treatment provided with ceftriaxone and azithromycin specific test should be treated for syphilis of unknown would have been sufficient to treat that infection. duration with benzathine penicillin once weekly for Oral amoxicillin is not recommended to treat syphilis three doses. (Option A). In countries where benzathine penicillin was not available, observational studies have demonstrated suc- Bibliography cessful treatment of syphilis with long-duration, high dose Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J oral amoxicillin combined with probenecid. This long oral Med. 2020:382:845-854. [PMID: gZtOtOOOI doi:10.1056iNEJMra1901593 194

lndex Note: Page numbers followed by f and t denote figure and table, respectively. Bocferoldes spp.,12 Test questions are indicated by Q. Balamuthia spp., 4 Baloxavir, for inlluenza infections, 98 A Basiliximab, immunosuppression by, 7 6t Abacavir, for HIV infection, 96t Boy lisoscori s procyonis, 4 Abscesses, llt,Q77 Bedaquiline, for tuberculosis, 36t Acanthamoeba spp., 4 Behget disease, meningitis caused by, 4 Acid-fast bacilli (AFB) smears, 33-34 Benzathine penicillin, 501, Q12, Q108 Acinetobacter spp., antibiotic resistant, 103, 104 Bichloroacetic acid, 51 Acute bacterial prostatitis, 31-32 Bictegraviq for HIV infection, 96t Acute flaccid myelitis, 6 Bioterrorism, agents of, 57-60, 57t Acute respiratory syndrome-coronaviruses (SARS-CoV), SS Bismuth subsalicylate, 65, 65t Acute retroviral syndrome, 89t, Q86 Bites, animal, 12-13, Q52 Acyclovir Bites, human,13, Q96 for HSV encephalitis, 7, Q62 Blacklegged ticks, 21-22, 22f , 25, 26t for HSV ulcers, 48t p-lactam agents, L7t, 20, 29 -3t, 86 for YZY encephalitis, 7 Blastomycosis,43, Q15 for YZY infections, 101, Q71 Bone mineral density, HIV and, 92 forVZY meningitis, 1 Borrelia burgdorferi, 2, 2L-25, Q16, Q99 Adalimumab, TB reactivation and, 37-38 Borrelia spp., 28t Adenoviruses, encephalitis and, 2 Botulism, 57t, 581, 59, Q103 Ae romonas hy drophila, 9t, lI Bourbon virus, 28t Alemtuzumab, immunosuppression by, 7 6t Brain abscesses, 5-6, 5t,6t,Q77 Amb lg o mma ame ricanum, 25 Brucellaspp., 53 Amebiasis diarrhea, 7Ot, 75 Brucellosis, 4, 6, 57t, 61t, 67-68, Q65 Amikacin, for tuberculosis, 36t B urkholde r ia mallei, 9 t

Note: Page numbers followed by f and t denote figure and table, respectively. Bocferoldes spp.,12 Test questions are indicated by Q. Balamuthia spp., 4 Baloxavir, for inlluenza infections, 98 A Basiliximab, immunosuppression by, 7 6t Abacavir, for HIV infection, 96t Boy lisoscori s procyonis, 4 Abscesses, llt,Q77 Bedaquiline, for tuberculosis, 36t Acanthamoeba spp., 4 Behget disease, meningitis caused by, 4 Acid-fast bacilli (AFB) smears, 33-34 Benzathine penicillin, 501, Q12, Q108 Acinetobacter spp., antibiotic resistant, 103, 104 Bichloroacetic acid, 51 Acute bacterial prostatitis, 31-32 Bictegraviq for HIV infection, 96t Acute flaccid myelitis, 6 Bioterrorism, agents of, 57-60, 57t Acute respiratory syndrome-coronaviruses (SARS-CoV), SS Bismuth subsalicylate, 65, 65t Acute retroviral syndrome, 89t, Q86 Bites, animal, 12-13, Q52 Acyclovir Bites, human,13, Q96 for HSV encephalitis, 7, Q62 Blacklegged ticks, 21-22, 22f , 25, 26t for HSV ulcers, 48t p-lactam agents, L7t, 20, 29 -3t, 86 for YZY encephalitis, 7 Blastomycosis,43, Q15 for YZY infections, 101, Q71 Bone mineral density, HIV and, 92 forVZY meningitis, 1 Borrelia burgdorferi, 2, 2L-25, Q16, Q99 Adalimumab, TB reactivation and, 37-38 Borrelia spp., 28t Adenoviruses, encephalitis and, 2 Botulism, 57t, 581, 59, Q103 Ae romonas hy drophila, 9t, lI Bourbon virus, 28t Alemtuzumab, immunosuppression by, 7 6t Brain abscesses, 5-6, 5t,6t,Q77 Amb lg o mma ame ricanum, 25 Brucellaspp., 53 Amebiasis diarrhea, 7Ot, 75 Brucellosis, 4, 6, 57t, 61t, 67-68, Q65 Amikacin, for tuberculosis, 36t B urkholde r ia mallei, 9 t Amoxicillin, l7t, 19, Q50, Q72 Amoxicillin-clavulanate, 13, 14, 20 c Amphotericin B, 4l-44, Q33, Q38 California encephalitis, 2 Ampicillin,2, Q48 Campylobacter diarrhea, 69 t, 7 o Anapl as m a phogoc y tophilum, 22, 26 Campylobacter infections, Q35, Q57 Anaplasmosis, 26-27, 26t Candida spp., 39-40 Angiostrongylus co ntonensis, 4 C. albicons infection, Q97 Anidulafungin, for candidiasis, 40 C. auris,87 Anorectal infections, 47 HIV and, 93,94f Anthrax infections, 57,57f,57t, 58, Q25 posttransplant infections, 78 Antibiotic-resistant organisms, 103-104 vertebral osteomyelitis and, 53 Antimicrobial stewardship, 103 Candidemia, diagnosis of, Q97 Anti-N-methyl-D-aspartate receptor encephalitis, 7 Candidiasis, 40, 4Ot, 78 Antipseudomonal pJactam, 6t Candiduria, 81-82 Antiretroviral treatment (ART), 95, Q21 CAP. See community-acquired pneumonia (CAP) Arboviruses, 7, 66-67, 66t Capnocytophaga canimorsus, 9t, 12, Q52 Area under the curve (AOC) dosing, Q89 Capreomycin, for tuberculosis, 36t Arenaviruses, bioterrorism and, 57t Carbapenemases, 103-104 Artemether-lumefantrine, 64t Carbapenems, 11, 14, 30-31 Artesunate, for malaria, Q54 Carbuncles, 8, 11t Aseptic meningitis, VZV and, 1 Carcinomas, meningitis caused bY, 4 Aspergillosis, 40- 42, 4lf, 4lt Cardiovascular disease, HIV and, 93 Aspergillus spp., 40 - 42, 78, Q84 Caspofungin, for candidiasis, 40 Aspiration pneumonia, Q7 Castleman disease, 94-95 Asymptomatic bacteriuria (ASB), 29, 30t, Q49 Cat bites, infected, 12 Atazanavir, for HIV infection, 96t Catheter-associated urinary tract infections (CAUTIs), 27, 80 - 82, 82t, Atovaquone /proguanil, 63t, 6 4t Q18, Q82 Autoimmune encephalitis, 7 Catheters, 27, 80 82, 82t Azathioprine, 76t Cefazolin, Q8, Q39 Azithromycin Cefepime, Q1, Qs9, Q8s for chancroid, 50t Cefpodoxime proxetil, for cystitis, Q1O0 for gonococcal infections, 45 Ceftaroline, for furuncle, 11t for infectious diarrhea, 69t, 70-71 Ceftazidime, Q4, Q13 for M. genitolium infection, 45 Ceftolozane-tazobactam, 104 for travelers' diarrhea, 65, 65t Ceftriaxone for typhoid fever, 62 for acute pyelonephritis, 30-31, Q19 for bacterial meningitis, Q48 B for brucellosis, 68 Bobesio microti,25 for infectious diarrhea, 69t,7L Babesiosis, 25, 25f, 251, Q83 for prostatitis, Q22 Bocillis anthracis, risk factors, 9t. See olso anthrax for STIs, 45, 501, Q2 Bacteremia,5, 14, 85-86, Q8 for typhoid fever,62 Bacterial endocarditis, 2 cellulftis, 8-10, 8f, 11t, Q39 Bacterial meningitis, 2, 3f, 3t, Q48 Central line-associated bloodstream infections (CIABSIs), 84-85, 841, Bacteriuria, 29, Q49 8st, Q1, Q32

Amoxicillin, l7t, 19, Q50, Q72 Amoxicillin-clavulanate, 13, 14, 20 c Amphotericin B, 4l-44, Q33, Q38 California encephalitis, 2 Ampicillin,2, Q48 Campylobacter diarrhea, 69 t, 7 o Anapl as m a phogoc y tophilum, 22, 26 Campylobacter infections, Q35, Q57 Anaplasmosis, 26-27, 26t Candida spp., 39-40 Angiostrongylus co ntonensis, 4 C. albicons infection, Q97 Anidulafungin, for candidiasis, 40 C. auris,87 Anorectal infections, 47 HIV and, 93,94f Anthrax infections, 57,57f,57t, 58, Q25 posttransplant infections, 78 Antibiotic-resistant organisms, 103-104 vertebral osteomyelitis and, 53 Antimicrobial stewardship, 103 Candidemia, diagnosis of, Q97 Anti-N-methyl-D-aspartate receptor encephalitis, 7 Candidiasis, 40, 4Ot, 78 Antipseudomonal pJactam, 6t Candiduria, 81-82 Antiretroviral treatment (ART), 95, Q21 CAP. See community-acquired pneumonia (CAP) Arboviruses, 7, 66-67, 66t Capnocytophaga canimorsus, 9t, 12, Q52 Area under the curve (AOC) dosing, Q89 Capreomycin, for tuberculosis, 36t Arenaviruses, bioterrorism and, 57t Carbapenemases, 103-104 Artemether-lumefantrine, 64t Carbapenems, 11, 14, 30-31 Artesunate, for malaria, Q54 Carbuncles, 8, 11t Aseptic meningitis, VZV and, 1 Carcinomas, meningitis caused bY, 4 Aspergillosis, 40- 42, 4lf, 4lt Cardiovascular disease, HIV and, 93 Aspergillus spp., 40 - 42, 78, Q84 Caspofungin, for candidiasis, 40 Aspiration pneumonia, Q7 Castleman disease, 94-95 Asymptomatic bacteriuria (ASB), 29, 30t, Q49 Cat bites, infected, 12 Atazanavir, for HIV infection, 96t Catheter-associated urinary tract infections (CAUTIs), 27, 80 - 82, 82t, Atovaquone /proguanil, 63t, 6 4t Q18, Q82 Autoimmune encephalitis, 7 Catheters, 27, 80 82, 82t Azathioprine, 76t Cefazolin, Q8, Q39 Azithromycin Cefepime, Q1, Qs9, Q8s for chancroid, 50t Cefpodoxime proxetil, for cystitis, Q1O0 for gonococcal infections, 45 Ceftaroline, for furuncle, 11t for infectious diarrhea, 69t, 70-71 Ceftazidime, Q4, Q13 for M. genitolium infection, 45 Ceftolozane-tazobactam, 104 for travelers' diarrhea, 65, 65t Ceftriaxone for typhoid fever, 62 for acute pyelonephritis, 30-31, Q19 for bacterial meningitis, Q48 B for brucellosis, 68 Bobesio microti,25 for infectious diarrhea, 69t,7L Babesiosis, 25, 25f, 251, Q83 for prostatitis, Q22 Bocillis anthracis, risk factors, 9t. See olso anthrax for STIs, 45, 501, Q2 Bacteremia,5, 14, 85-86, Q8 for typhoid fever,62 Bacterial endocarditis, 2 cellulftis, 8-10, 8f, 11t, Q39 Bacterial meningitis, 2, 3f, 3t, Q48 Central line-associated bloodstream infections (CIABSIs), 84-85, 841, Bacteriuria, 29, Q49 8st, Q1, Q32 195

lndex Central nervous system (CNS), 1-8, 42. See olso encephalitis; meningitis postinfluenza, 15-16 Central venous catheters (CVCs), Q32 risk factors for, 16t Cephalexin,14 severe, Q59 Cephalosporins Complement deficiencies, 55t, Q14 for brain abscesses, 6t Condyloma lata,49,49f for cellulitis, 11t Coronaviruses, respiratory infections, 98-99 for erysipelas, 11t Coxiella burnetii, 16, 18, 61t for gonococcal infections, 45 Cranial abscesses, 5 for HAP and VAP, 86 Cranial neuropathies, autoimmune, 7 Cerebellitis, autoimmune, 7 Cryotherapy, for genital warts, 51 Cerebrospinal fluid (CSF) Cryptococcal meningitis, Q38, Q66 flndings in meningitis, 1t C44ptococcosis, 42, 42t, 78 hemorrhagic, 1 Cryptococcus infections, 94 lymphocytic pleocytosis, 1, 4 Cryptococcus neoformans, 4 Certolizumab, TB reactivation and, 37 38 Cryptosporidium diarrhea, 7Ot, 74-7 5, Q88 Cervicitis, 45,46t CURB-65 scoring, 19 Chancroid, 50, 50t Cyclophosphamide, immunosuppression by, 76t Chest radiography, in CAP diagnosis, 17-18, 18t Cycloserine, for tuberculosis, 36t Chickenpox, 100-101 Cyclospora diarrhea, 7 Ot, 7 5 Chikungunya, 6lt, 66 - 67 Cyclosporine, immunosuppression by, 76t Chlamydia, screening for, Q60 Cystitis, 27, 29 -3o, Q36, Q100 Chlamydiaspp., 44-45, 46t, Q3 Cy'tomegalovirus (CMV) Chlamy do phila p ne umo niqe, L6, 18 diagnosis ol Q26, Q58 Chloramphenicol, 58t encephalitis caused by, 7 Chloroquine, 63t, 64t features of, 611, 99t, lol-102, l}2f Chloroquine phosphate, 64t HIV and, 94 Chronic granulomatous meningitis, 4 meningitis caused by, 1 Chronic kidney disease, in HIV infection, 92 posttransplant, 7 8, Q26 Chronic stasis dermatitis, 10f valganciclovir for, Q63 Cidofovir, for CMV 102 Ciprofloxacin D for acute pyelonephritis, 30-31 Daclizumab, immunosuppression by, 7 6t for anthrax infections, 58t Dalbavancin, for MRSA skin infections, 12 for chancroid, 50t Daptomycin, 6t, 11, 11t, 14, 85 for folliculitis, 11t Darunavir,89,96t for infectious diarrhea, 69t,71 Delafloxacin, for MRSA skin infections, 12 precautions, Q73 Dementia, HIV encephalitis and, 7 for travelers' diarrhea, 65t Demodexspp.,ll-12 for tularemia, 58t Dengue fever, 61t, 66-67, 66f, Q47 for typhoid fever, 62 Dexamethasone, for meningitis, 2, Q48 for VAP, Q4 Diabetic foot infections, 13-15, 52-53, Q79 Clindamycin Diarrhea for bite wounds, 13 C. dfficile,Q6r for C. perfringens NF, Q20 deflnition of, 68 for cellulitis, 11t E coli related, Q17 for diabetic foot infections, 14 fldaxomicin for, Q95 for erysipelas, 11t infectious, 68, 69t-7ot, 70 for folliculitis, l1t Dicloxacillin, llt, 14 for malaria, 64t Diloxanide, for amebiasis, 75 for MRSA infections. 14 Diphenoxylate, for travelers' diarrhea, 65 for PID, Q92 Dolutegravir, 88, 89, 96t resistance to, 14 Doxycycline for S. oureus infections, 14 after anthrax exposure, Q25 for skin infections, 11 for anthrax infections, 58t for TSS, 14 for bite wounds, 13 Clostridioides dfficile for brucellosis, 68 antibiotic-resistant, 87 for CAB 77t,19,20 diarrhea, 69t, 72-74, 73f, 73t, 74t, Q95 for diabetic foot infections, 14 incidence of, 80 for infectious diarrhea, 69t,72 management of, Q10, Q61, Q95 for LGV 50t posttransplant infections, 78 for Lyme disease, Q16 Clostridium spp. for MSSA, Q87 C. botulinum, SB prophylactic, 63t C. perfringens, 9t, Q20 for tick borne diseases, 26-27,26t NF caused by, 11 for tularemia, 58t Clotrimazole, for Cqndida in HIV 93 for Vibrio infection, Q13 Cobicistat, for HIV infection, 96t Drug-resistant tuberculosis, 37 Coccidioides immitis, 4 Coccidioidomycosis, 43, Q9B I Colistin, 86, 104 Ebola, 571, 58, 6O Colorado tick fever virus, 28t Echinocandins, for candidiasis, 40 Common variable immunodeficiency (CVID), 55-56, SSt, e27 Eculizumab, adverse effects o[ 56t Community-acquired pneumonia (CAP), 14-21 Efavirenz, for HIV infection, 96t aspiration pneumonia and, Q7 Ehrlichio spp. clinical decision support scoring, 19t E. chaffeensis,26 complications of, 21, 21t E. ewingii,2St diagnostic evaluation of , 17 -19 muris e quclairensis, 28t epidemiologz of, 14-15 Ehrlichiosis, 26-27, 26f, 26t influenza and, Q64 Eikenella corodens,l3 management of,l7t,I9-2O, Q11, QS9, e72 Electroencephalography, 7 microbiologz of, 15-16 Elvitegravir, for HIV infection, 96t pathogens causing, 161, 181 e3 Empyema, management of, Q9

Central nervous system (CNS), 1-8, 42. See olso encephalitis; meningitis postinfluenza, 15-16 Central venous catheters (CVCs), Q32 risk factors for, 16t Cephalexin,14 severe, Q59 Cephalosporins Complement deficiencies, 55t, Q14 for brain abscesses, 6t Condyloma lata,49,49f for cellulitis, 11t Coronaviruses, respiratory infections, 98-99 for erysipelas, 11t Coxiella burnetii, 16, 18, 61t for gonococcal infections, 45 Cranial abscesses, 5 for HAP and VAP, 86 Cranial neuropathies, autoimmune, 7 Cerebellitis, autoimmune, 7 Cryotherapy, for genital warts, 51 Cerebrospinal fluid (CSF) Cryptococcal meningitis, Q38, Q66 flndings in meningitis, 1t C44ptococcosis, 42, 42t, 78 hemorrhagic, 1 Cryptococcus infections, 94 lymphocytic pleocytosis, 1, 4 Cryptococcus neoformans, 4 Certolizumab, TB reactivation and, 37 38 Cryptosporidium diarrhea, 7Ot, 74-7 5, Q88 Cervicitis, 45,46t CURB-65 scoring, 19 Chancroid, 50, 50t Cyclophosphamide, immunosuppression by, 76t Chest radiography, in CAP diagnosis, 17-18, 18t Cycloserine, for tuberculosis, 36t Chickenpox, 100-101 Cyclospora diarrhea, 7 Ot, 7 5 Chikungunya, 6lt, 66 - 67 Cyclosporine, immunosuppression by, 76t Chlamydia, screening for, Q60 Cystitis, 27, 29 -3o, Q36, Q100 Chlamydiaspp., 44-45, 46t, Q3 Cy'tomegalovirus (CMV) Chlamy do phila p ne umo niqe, L6, 18 diagnosis ol Q26, Q58 Chloramphenicol, 58t encephalitis caused by, 7 Chloroquine, 63t, 64t features of, 611, 99t, lol-102, l}2f Chloroquine phosphate, 64t HIV and, 94 Chronic granulomatous meningitis, 4 meningitis caused by, 1 Chronic kidney disease, in HIV infection, 92 posttransplant, 7 8, Q26 Chronic stasis dermatitis, 10f valganciclovir for, Q63 Cidofovir, for CMV 102 Ciprofloxacin D for acute pyelonephritis, 30-31 Daclizumab, immunosuppression by, 7 6t for anthrax infections, 58t Dalbavancin, for MRSA skin infections, 12 for chancroid, 50t Daptomycin, 6t, 11, 11t, 14, 85 for folliculitis, 11t Darunavir,89,96t for infectious diarrhea, 69t,71 Delafloxacin, for MRSA skin infections, 12 precautions, Q73 Dementia, HIV encephalitis and, 7 for travelers' diarrhea, 65t Demodexspp.,ll-12 for tularemia, 58t Dengue fever, 61t, 66-67, 66f, Q47 for typhoid fever, 62 Dexamethasone, for meningitis, 2, Q48 for VAP, Q4 Diabetic foot infections, 13-15, 52-53, Q79 Clindamycin Diarrhea for bite wounds, 13 C. dfficile,Q6r for C. perfringens NF, Q20 deflnition of, 68 for cellulitis, 11t E coli related, Q17 for diabetic foot infections, 14 fldaxomicin for, Q95 for erysipelas, 11t infectious, 68, 69t-7ot, 70 for folliculitis, l1t Dicloxacillin, llt, 14 for malaria, 64t Diloxanide, for amebiasis, 75 for MRSA infections. 14 Diphenoxylate, for travelers' diarrhea, 65 for PID, Q92 Dolutegravir, 88, 89, 96t resistance to, 14 Doxycycline for S. oureus infections, 14 after anthrax exposure, Q25 for skin infections, 11 for anthrax infections, 58t for TSS, 14 for bite wounds, 13 Clostridioides dfficile for brucellosis, 68 antibiotic-resistant, 87 for CAB 77t,19,20 diarrhea, 69t, 72-74, 73f, 73t, 74t, Q95 for diabetic foot infections, 14 incidence of, 80 for infectious diarrhea, 69t,72 management of, Q10, Q61, Q95 for LGV 50t posttransplant infections, 78 for Lyme disease, Q16 Clostridium spp. for MSSA, Q87 C. botulinum, SB prophylactic, 63t C. perfringens, 9t, Q20 for tick borne diseases, 26-27,26t NF caused by, 11 for tularemia, 58t Clotrimazole, for Cqndida in HIV 93 for Vibrio infection, Q13 Cobicistat, for HIV infection, 96t Drug-resistant tuberculosis, 37 Coccidioides immitis, 4 Coccidioidomycosis, 43, Q9B I Colistin, 86, 104 Ebola, 571, 58, 6O Colorado tick fever virus, 28t Echinocandins, for candidiasis, 40 Common variable immunodeficiency (CVID), 55-56, SSt, e27 Eculizumab, adverse effects o[ 56t Community-acquired pneumonia (CAP), 14-21 Efavirenz, for HIV infection, 96t aspiration pneumonia and, Q7 Ehrlichio spp. clinical decision support scoring, 19t E. chaffeensis,26 complications of, 21, 21t E. ewingii,2St diagnostic evaluation of , 17 -19 muris e quclairensis, 28t epidemiologz of, 14-15 Ehrlichiosis, 26-27, 26f, 26t influenza and, Q64 Eikenella corodens,l3 management of,l7t,I9-2O, Q11, QS9, e72 Electroencephalography, 7 microbiologz of, 15-16 Elvitegravir, for HIV infection, 96t pathogens causing, 161, 181 e3 Empyema, management of, Q9 196

lndex Emtricitabine, 88, 96t, Q29 Giardia diarrhea, 70t Encephalitis,6 7 Giardia lamblia infection. 74 Japanese,61t,68, Q43 Glanders, bioterrorism and, 57t management of,7,Q62 Glucocorticoids, 7, 56t tick-borne, 611, 68 Gnqthostoma meningitis, 4 viral, 1, 2,7,Q42,Q75 Gonorrhea, screening for, Q60 Endocarditis, bacterial, 2 Graft uersus-host disease (GVHD), ZS zO Entamoeba histolg tica, 7 S Guillain-Barre syndrome (GBS), Q3S Entecavir, prophylactic, Q41 Enterobacteriaceae, 28 H Enterococcus faecium, antibiotic resistant, 103 Haemophilus influenzae, 2, 16 Enterotoxin A, 73 "Halo sign," 41f Enterovirus meningitis, 1, Q106 Hantavirus, bioterrorism and. 57t Epididymitis, 46t, 47 Hantavirus, CAP and, 16 Epstein-Barr virus Health care associated infections (UCAI), 80 g7, 8it, egs clinical clues, 61t Health care-associated meningitis and ventriculitis, 5, egS diagnosis of, Q55, Q76 Health care-associated pneumonia (HCAP), fS encephalitis caused by, 7 Heartland virus, 28t, Q7O features of. 101 Helminth meningitis, 4 manifestations of, 99t Hematopoietic stem cell transplantation (HSCT) , ZZ , zzt meningitis caused by, 1 Hemochromatosis. 72 posttransplant infections, 78 Hemolytic uremic syndrome (HUS), 72,Q17 posttransplant lymphoproliferative disorder related to, e76 Hepatitisviruses, 67,93, Q4i, Q56 Ertapenem,30-31, Q53 Herpes gladiatorum, 100 Erthyema multiforme, HSV and, 100 Herpes lymphotropic virus, 99t Eravacycline, 104, 105t Herpes simplex viruses (HSV). 99t, 100 Erysipelas, 8 10, 81 11t encephalitis, 7, Q62 Ery sip elothr ix rhusiopathiae, 9t folliculitis caused by, 11 Erythema migrans (EM).2. 22.22f genital ulcers, 47-48,481 48t Erlthema nodosum, 10f meningitis,l, Q80 Erythromycin, 50t recurrent genital ulcers and, Q44 Escherichie coli transmission of, 100 diarrhea, 69t, 7l-72, 7It, Ql7 Herpes zoster (shingles), 100, Q71, QB1 diarrheagenic strains of, 71t Herpesviruses, meningitis caused by, 1 enterohemorrhagic strains of, 72 Herpetic whitlow, 100 spinal epidural abscesses and, 5-6 Histoplasma capsulatum, 4, 42-43 traveler's diarrhea and, 65 Histoplasmosis, 42 43, 6it, 78. Q33 UTIs and, 28 HIV/AIDS,87 97 Etanercept, TB reactivation and, 37-38 antiretroviral agents used for, 96t Ethambutol, 36t, 37t, Q23 aseptic meningitis and, 2 Ethionamide, for tuberculosis, 36t CAP and, 18 Etravirine, for HIV infection, 96t complications of, 92-95 Everolimus, immunosuppression by, 7 6t diagnosis of, 89-90, 90f Extended-spectrum B lactamase (ESBL), 103-104 encephalitis caused by, 7 false positive testing for, Q93 t initiation of care in.90 92 Facial nerve palsy, Q16 management of infection, 95 96, Q21 Famciclovir, for VSV infections, 101 natural history of, 89 Fever of unknown origin, 54-55, 54t, Q67 opportunistic infections in, 90, 92,92t Fidaxomicin, for infectious diarrhea, 691, 73, Q95 pathophysiologr of, 89 Filoviruses, bioterrorism and, 57t postexposure prophylaxis, BB, BBf Flaviviruses,68 pregnant patients with,96 97 Fluconazole,42,43 prevention ol 87 89,89t, Q29 Flucytosine,42, Q38 screening for, 89 90, 91t, Q60 Fluoroquinolones sexual practice counseling, Q93 for acute bacterial prostatitis, 31 32 signs of acute infection, 89t for acute pyelonephritis, 30-31 transmission risk, 871, Q5 adverse effects ol Q73 tuberculosis risk and, Q69 for bite wounds, 13 vaccinations in people with, Q24 for CAP, l7t,20 HlV-associated dementia (HAD), 93 for diabetic foot infections, 14 HIV associated neurocognitive decline (HAND), 93 for infectious diarrhea, 69t, 71, 72 Hospital acquired pneumonia (HAP), 15, 86-87, Q1o7 for travelers' diarrhea, 65 Human herpesviruses (HHVs), l, 94, 99 lo2, 99t for [zphoid fever, 62 Human metapneumovirus, 97t for UTIs, 29-30 Human papillomavirus (HPV) infection, 51, 51f Folliculitis, 8, 11 12, 111, 121 Q40 Hydrocephalus, obstructive, 4f Foot infections, diabetes and, 13-15, 52 53, Q79 Hydroxychloroquine, 63t, 641 Foscarnet, for CMY 102 Hyperlipidemia, HIV and, 92 Fosfomycin, activiff of, 104 Francisella tularensis,9t, 16, i8, 58-60 I Fungal infections, 39-44 Imipenem, 11t,30-31 Fungal meningitis, 4 Imiquimod,5l Furuncles, B, 11t Immune globulin, IV, meningitis caused by, ,1 Fusobacterium spp., 12, 13 Immune reconstitution inflammatory syndrome (IRIS), 37, 93 Immunizations. travel and, 6ot G Immunocompromise Galactomannan assay, 41 animal bites in, 13 Ganciclovir, for CMV 102 asymptomatic bacteriuria in, Qa9 Gastrointestinal syndromes, infectious, 68-75 brain abscesses and, 5 Genital ulcers, 47-50, Q44 C cqnimorsus infection in, Q52 Genital warts, 50 51, 51f Campglobacter infections in, Q57 Gentamicin, 45, 581, Q92 cryptococcosis and, 42

Emtricitabine, 88, 96t, Q29 Giardia diarrhea, 70t Encephalitis,6 7 Giardia lamblia infection. 74 Japanese,61t,68, Q43 Glanders, bioterrorism and, 57t management of,7,Q62 Glucocorticoids, 7, 56t tick-borne, 611, 68 Gnqthostoma meningitis, 4 viral, 1, 2,7,Q42,Q75 Gonorrhea, screening for, Q60 Endocarditis, bacterial, 2 Graft uersus-host disease (GVHD), ZS zO Entamoeba histolg tica, 7 S Guillain-Barre syndrome (GBS), Q3S Entecavir, prophylactic, Q41 Enterobacteriaceae, 28 H Enterococcus faecium, antibiotic resistant, 103 Haemophilus influenzae, 2, 16 Enterotoxin A, 73 "Halo sign," 41f Enterovirus meningitis, 1, Q106 Hantavirus, bioterrorism and. 57t Epididymitis, 46t, 47 Hantavirus, CAP and, 16 Epstein-Barr virus Health care associated infections (UCAI), 80 g7, 8it, egs clinical clues, 61t Health care-associated meningitis and ventriculitis, 5, egS diagnosis of, Q55, Q76 Health care-associated pneumonia (HCAP), fS encephalitis caused by, 7 Heartland virus, 28t, Q7O features of. 101 Helminth meningitis, 4 manifestations of, 99t Hematopoietic stem cell transplantation (HSCT) , ZZ , zzt meningitis caused by, 1 Hemochromatosis. 72 posttransplant infections, 78 Hemolytic uremic syndrome (HUS), 72,Q17 posttransplant lymphoproliferative disorder related to, e76 Hepatitisviruses, 67,93, Q4i, Q56 Ertapenem,30-31, Q53 Herpes gladiatorum, 100 Erthyema multiforme, HSV and, 100 Herpes lymphotropic virus, 99t Eravacycline, 104, 105t Herpes simplex viruses (HSV). 99t, 100 Erysipelas, 8 10, 81 11t encephalitis, 7, Q62 Ery sip elothr ix rhusiopathiae, 9t folliculitis caused by, 11 Erythema migrans (EM).2. 22.22f genital ulcers, 47-48,481 48t Erlthema nodosum, 10f meningitis,l, Q80 Erythromycin, 50t recurrent genital ulcers and, Q44 Escherichie coli transmission of, 100 diarrhea, 69t, 7l-72, 7It, Ql7 Herpes zoster (shingles), 100, Q71, QB1 diarrheagenic strains of, 71t Herpesviruses, meningitis caused by, 1 enterohemorrhagic strains of, 72 Herpetic whitlow, 100 spinal epidural abscesses and, 5-6 Histoplasma capsulatum, 4, 42-43 traveler's diarrhea and, 65 Histoplasmosis, 42 43, 6it, 78. Q33 UTIs and, 28 HIV/AIDS,87 97 Etanercept, TB reactivation and, 37-38 antiretroviral agents used for, 96t Ethambutol, 36t, 37t, Q23 aseptic meningitis and, 2 Ethionamide, for tuberculosis, 36t CAP and, 18 Etravirine, for HIV infection, 96t complications of, 92-95 Everolimus, immunosuppression by, 7 6t diagnosis of, 89-90, 90f Extended-spectrum B lactamase (ESBL), 103-104 encephalitis caused by, 7 false positive testing for, Q93 t initiation of care in.90 92 Facial nerve palsy, Q16 management of infection, 95 96, Q21 Famciclovir, for VSV infections, 101 natural history of, 89 Fever of unknown origin, 54-55, 54t, Q67 opportunistic infections in, 90, 92,92t Fidaxomicin, for infectious diarrhea, 691, 73, Q95 pathophysiologr of, 89 Filoviruses, bioterrorism and, 57t postexposure prophylaxis, BB, BBf Flaviviruses,68 pregnant patients with,96 97 Fluconazole,42,43 prevention ol 87 89,89t, Q29 Flucytosine,42, Q38 screening for, 89 90, 91t, Q60 Fluoroquinolones sexual practice counseling, Q93 for acute bacterial prostatitis, 31 32 signs of acute infection, 89t for acute pyelonephritis, 30-31 transmission risk, 871, Q5 adverse effects ol Q73 tuberculosis risk and, Q69 for bite wounds, 13 vaccinations in people with, Q24 for CAP, l7t,20 HlV-associated dementia (HAD), 93 for diabetic foot infections, 14 HIV associated neurocognitive decline (HAND), 93 for infectious diarrhea, 69t, 71, 72 Hospital acquired pneumonia (HAP), 15, 86-87, Q1o7 for travelers' diarrhea, 65 Human herpesviruses (HHVs), l, 94, 99 lo2, 99t for [zphoid fever, 62 Human metapneumovirus, 97t for UTIs, 29-30 Human papillomavirus (HPV) infection, 51, 51f Folliculitis, 8, 11 12, 111, 121 Q40 Hydrocephalus, obstructive, 4f Foot infections, diabetes and, 13-15, 52 53, Q79 Hydroxychloroquine, 63t, 641 Foscarnet, for CMY 102 Hyperlipidemia, HIV and, 92 Fosfomycin, activiff of, 104 Francisella tularensis,9t, 16, i8, 58-60 I Fungal infections, 39-44 Imipenem, 11t,30-31 Fungal meningitis, 4 Imiquimod,5l Furuncles, B, 11t Immune globulin, IV, meningitis caused by, ,1 Fusobacterium spp., 12, 13 Immune reconstitution inflammatory syndrome (IRIS), 37, 93 Immunizations. travel and, 6ot G Immunocompromise Galactomannan assay, 41 animal bites in, 13 Ganciclovir, for CMV 102 asymptomatic bacteriuria in, Qa9 Gastrointestinal syndromes, infectious, 68-75 brain abscesses and, 5 Genital ulcers, 47-50, Q44 C cqnimorsus infection in, Q52 Genital warts, 50 51, 51f Campglobacter infections in, Q57 Gentamicin, 45, 581, Q92 cryptococcosis and, 42 197

lndex Immunocompromise (Co ntinue d) enterovirus, Q1O6 encephalitis and, 7 evaluation, 2 pretravel vaccinations in, Q56 health care-associated, Q85 prevention of HBV reactivation, Q41 herpes simplex-related, Q80 VZV transmission and, Q45 management of, 2 Immunodeficiency s5mdromes, 55-57, 55t, 56t subacute,4 Immunosuppressive agents, 76t Meningoencephalitis, 7, 27 Infliximab, TB reactivation and, 37-38 Meropenem, 111, 30-31 Influenza viruses, 2, 15, 18, 97-98, Q37, Q46, Q64 Meropenem-vaborbactam, 104, 1051 Insulin resistance, HIV and, 92 Methicillin-resistant S. oureus (MRSA), 8, 8f,12, 20,53, 85, Q4 Interferon-lrelease assay (IGRA), Q74 Methicillin-sensitive S. oureus (MSSA), 85, Q8, Q87 Isavuconazole, 4l, 44 Methotrexate, immunosuppression by, 76t Isoniazid, 35, 36t, 371, Q23, Q78 Metronidazole Itraconazole, 43 choice in penicillin allergr, Q96 Ixodes ticks, 21, 22f, 25, 26, 26t for bite wounds, 13 for brain abscesses, 6t J for C. dfficile diarrhea, Q61 Japanese encephalitis, 61t, 68, Q43 for diabetic foot infections, 14 for Giardiq infection, 74 K for infectious diarrhea, 69t, 7Ot, 73 Kanamycin, for tuberculosis, 36t Micafungin, for candidiasis, 40 Kaposi sarcoma, 94,95f Microangiopathic hemolytic anemia, 72 Kaposi sarcoma associated virus, 99t Middle East respiratory syndrome (MERS-CoV), 61t,99 Keratoconjunctivitis, 100 Miltefosine, for parasitic meningitis, 4 Kle b s iella p neumoniae, LO 3 Minocycline,l04 Koplik spots, 1O2f Mites, folliculitis caused by, ll-12 Mollaret meningitis, 1 t Mononucleosis syndrome, 61t Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), 10-11 Morulae,26f La Crosse viruses, 7 Mosquitoes, arboviruses and, 66-67 Lamivudine, for HIV infection, 96t Moxifloxacin, 361, 58t Lassa fever, bioterrorism and, 57t Mucor, posttransplant infections, 78 Latent tuberculosis infection (LTBI), 33-34, 35t, Q78 Mucormycosis, 44, 44f, Q90 Legionellaspp., 16, 18, Q68 Multidrug resistant organisms (MDROs), 87 Legionellosis, 61t Multidrug-resistant infections, Q53 Leishmania, posttransplant, 78 Multidrug-resistant tuberculosis (MDR{B), 32 Leptospiral meningitis, 2 Mumps,2,103 Leptospirosis, 61t Mupirocin, for folliculitis, 11t Letermovir, 80, 102 Muromonab, immunosuppression by, 76t Leukemias, meningitis caused by, 4 Mycobacteria, nontuberculous, 38t Leukocyte esterase, 29 Mycobacterium au ium complex (MAC), Q30 Levofloxacin Mycobacterium spp. choice in penicillin allerry, Q96 M. obscessus, 39, 39t for acute pyelonephritis, 30-31 M. auium, 38-39, 39t, 92, 92t, 94 for anthrax infections, 58t M. chelonqe,59 for CAP, Q7, Q11 M. fortuitum,9t,39t for severe CAB Q59 M. konsosii,39,39t for travelers' diarrhea, 65t M. marinum,9t for tuberculosis, 36t M. tuberculosis,4, 32-39, 53, Q23, Q69, Q78, Q1O1 Linezolid, llt, 14, l7t, 20, 86 Mycophenolate mofetil, 76t Listeria monocAtogenes meningitis, 2 Mycophenolate sodium, 76t Liver disease, HIV and, 93 Mycoplasma spp., 16, 18, 45 Loperamide, for travelers' diarrhea, 65 Myelitis, YZY and,l Lopinavir, for HIV infection, 96t Lumbar puncture, diagnostic, Q66 t{ Lyme disease,2l-25 N95 respirators, 81f clinical clues, 2, 23t,6lt Naegleriaspp.,4 distribution of,22f Nafcillin, for S. oureus infections, 14 management of, Q6 Natalizumab, adverse effects of, 56t serologic testing for, 24f Necrotizing fasciitis (NF), 10-11, 111, Q13, Q20 Lyme meningitis, Q99 Neisseria spp. Lyme myocarditis, 22 23 N. gonorrhoeae, 44-45, 46t, Q2 Lymphocytic choriomeningitis virus, 2 N. meningitidis,2 Lymphocytic pleocytosis, 4 Nephrolithiasis, 29 Lymphogranuloma venereum (LGV), 50, 50t Neuraminidase inhibitors, 98 Neurobrucellosis, 4 M Neurocognitive decline, HIV and, 93 Machupo, bioterrorism and, 57t Neurocysticercosis, 4, 4t, Q94 Macrolide, for CAB l7t,20 Neurosarcoidosis, 4 Malaria, 60, 61t, 63t, 641, Q54 Neurosyphilis,2,49 Malassezia, folliculitis, 11 Nevirapine, for HIV infection, 96t Maraviroc, for HIV 96t Nipah virus, bioterrorism and, 57t Marburg virus, 571, 58, 60 Nitazoxanide, 7 Ot, 74, 75, Q88 Measles, encephalitis and, 2 Nitrofurantoin, for UTIs, 29, Q36 Measles-mumps-rubella (MMR) vaccine, 103 Non-Hodgkin lymphoma, HIV and, 94 Mefloquine,63t Nontuberculous mycobacteria (NTM), 38-39, 381, 39t Melioidosis, bioterrorism and, 57t Norfloxacin, for travelers' diarrhea, 65t Meningitis, 1-5 Norovirus diarrhea, 69t, 74 Borrelia burgdorferi-associated, Q99 Nosocomial meningitis, 5 caused by antibiotics, 4 NSAIDS, meningitis caused by, 4 chronic,4 Nucleic acid amplificaiton testing (NAAT), 44-45, c44ptococcal, Q3B, Q66 Q64, Q86

Immunocompromise (Co ntinue d) enterovirus, Q1O6 encephalitis and, 7 evaluation, 2 pretravel vaccinations in, Q56 health care-associated, Q85 prevention of HBV reactivation, Q41 herpes simplex-related, Q80 VZV transmission and, Q45 management of, 2 Immunodeficiency s5mdromes, 55-57, 55t, 56t subacute,4 Immunosuppressive agents, 76t Meningoencephalitis, 7, 27 Infliximab, TB reactivation and, 37-38 Meropenem, 111, 30-31 Influenza viruses, 2, 15, 18, 97-98, Q37, Q46, Q64 Meropenem-vaborbactam, 104, 1051 Insulin resistance, HIV and, 92 Methicillin-resistant S. oureus (MRSA), 8, 8f,12, 20,53, 85, Q4 Interferon-lrelease assay (IGRA), Q74 Methicillin-sensitive S. oureus (MSSA), 85, Q8, Q87 Isavuconazole, 4l, 44 Methotrexate, immunosuppression by, 76t Isoniazid, 35, 36t, 371, Q23, Q78 Metronidazole Itraconazole, 43 choice in penicillin allergr, Q96 Ixodes ticks, 21, 22f, 25, 26, 26t for bite wounds, 13 for brain abscesses, 6t J for C. dfficile diarrhea, Q61 Japanese encephalitis, 61t, 68, Q43 for diabetic foot infections, 14 for Giardiq infection, 74 K for infectious diarrhea, 69t, 7Ot, 73 Kanamycin, for tuberculosis, 36t Micafungin, for candidiasis, 40 Kaposi sarcoma, 94,95f Microangiopathic hemolytic anemia, 72 Kaposi sarcoma associated virus, 99t Middle East respiratory syndrome (MERS-CoV), 61t,99 Keratoconjunctivitis, 100 Miltefosine, for parasitic meningitis, 4 Kle b s iella p neumoniae, LO 3 Minocycline,l04 Koplik spots, 1O2f Mites, folliculitis caused by, ll-12 Mollaret meningitis, 1 t Mononucleosis syndrome, 61t Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), 10-11 Morulae,26f La Crosse viruses, 7 Mosquitoes, arboviruses and, 66-67 Lamivudine, for HIV infection, 96t Moxifloxacin, 361, 58t Lassa fever, bioterrorism and, 57t Mucor, posttransplant infections, 78 Latent tuberculosis infection (LTBI), 33-34, 35t, Q78 Mucormycosis, 44, 44f, Q90 Legionellaspp., 16, 18, Q68 Multidrug resistant organisms (MDROs), 87 Legionellosis, 61t Multidrug-resistant infections, Q53 Leishmania, posttransplant, 78 Multidrug-resistant tuberculosis (MDR{B), 32 Leptospiral meningitis, 2 Mumps,2,103 Leptospirosis, 61t Mupirocin, for folliculitis, 11t Letermovir, 80, 102 Muromonab, immunosuppression by, 76t Leukemias, meningitis caused by, 4 Mycobacteria, nontuberculous, 38t Leukocyte esterase, 29 Mycobacterium au ium complex (MAC), Q30 Levofloxacin Mycobacterium spp. choice in penicillin allerry, Q96 M. obscessus, 39, 39t for acute pyelonephritis, 30-31 M. auium, 38-39, 39t, 92, 92t, 94 for anthrax infections, 58t M. chelonqe,59 for CAP, Q7, Q11 M. fortuitum,9t,39t for severe CAB Q59 M. konsosii,39,39t for travelers' diarrhea, 65t M. marinum,9t for tuberculosis, 36t M. tuberculosis,4, 32-39, 53, Q23, Q69, Q78, Q1O1 Linezolid, llt, 14, l7t, 20, 86 Mycophenolate mofetil, 76t Listeria monocAtogenes meningitis, 2 Mycophenolate sodium, 76t Liver disease, HIV and, 93 Mycoplasma spp., 16, 18, 45 Loperamide, for travelers' diarrhea, 65 Myelitis, YZY and,l Lopinavir, for HIV infection, 96t Lumbar puncture, diagnostic, Q66 t{ Lyme disease,2l-25 N95 respirators, 81f clinical clues, 2, 23t,6lt Naegleriaspp.,4 distribution of,22f Nafcillin, for S. oureus infections, 14 management of, Q6 Natalizumab, adverse effects of, 56t serologic testing for, 24f Necrotizing fasciitis (NF), 10-11, 111, Q13, Q20 Lyme meningitis, Q99 Neisseria spp. Lyme myocarditis, 22 23 N. gonorrhoeae, 44-45, 46t, Q2 Lymphocytic choriomeningitis virus, 2 N. meningitidis,2 Lymphocytic pleocytosis, 4 Nephrolithiasis, 29 Lymphogranuloma venereum (LGV), 50, 50t Neuraminidase inhibitors, 98 Neurobrucellosis, 4 M Neurocognitive decline, HIV and, 93 Machupo, bioterrorism and, 57t Neurocysticercosis, 4, 4t, Q94 Macrolide, for CAB l7t,20 Neurosarcoidosis, 4 Malaria, 60, 61t, 63t, 641, Q54 Neurosyphilis,2,49 Malassezia, folliculitis, 11 Nevirapine, for HIV infection, 96t Maraviroc, for HIV 96t Nipah virus, bioterrorism and, 57t Marburg virus, 571, 58, 60 Nitazoxanide, 7 Ot, 74, 75, Q88 Measles, encephalitis and, 2 Nitrofurantoin, for UTIs, 29, Q36 Measles-mumps-rubella (MMR) vaccine, 103 Non-Hodgkin lymphoma, HIV and, 94 Mefloquine,63t Nontuberculous mycobacteria (NTM), 38-39, 381, 39t Melioidosis, bioterrorism and, 57t Norfloxacin, for travelers' diarrhea, 65t Meningitis, 1-5 Norovirus diarrhea, 69t, 74 Borrelia burgdorferi-associated, Q99 Nosocomial meningitis, 5 caused by antibiotics, 4 NSAIDS, meningitis caused by, 4 chronic,4 Nucleic acid amplificaiton testing (NAAT), 44-45, c44ptococcal, Q3B, Q66 Q64, Q86 198

lndex o management of infections, e4, e40, e59 Obiltoxaximab, for anthrax, 5gt risk factors associated with. 9t Ofloxacin, for travelers' diarrhea, 65t vertebral osteomyelitis and, 53 Omadacycline, 12, 104, 1051 Psittacosis, bioterrorism and, 57t Oritavancin, for MRSA, 12 Purpura fulminans, 27 Oseltamivir, for influenza, 9g, e46 Pyelonephritis, 27, 30-31, Q19 Osteomyelitis, 51-53 Pyrazinamide, 36t, 371, Q23 biopsy of, Q91 Pyridoxine. for LTBI, 35 diabetic foot infections and, 52-53, e79 Pyuria, diagnosis of, 28-29 diagnosis of, S1-S2, Q34 imaging in,52f, Q79 o manifestations of, 51 Q fever, 57t,67t MSSA-related, Q87 Quinine sulfate, 64t treatment of, 52, Q28 Quinolones, adverse effects of, 20 vertebral,53, Q28, Q34 R Otitis media, 5 Outpatient parenteral antibiotic therapy (OPAT), 104 Rabies, clinical clues, 61t Ovarian teratomas, 7 Radiculopathy, Lyme disease and, 23 Oxacillin, for S. oureus infections, 14 Raltegravir, 88, 96t Ramsay Hunt syndrome, 101, 101f, QB1 P Raxibacumab, for anthrax, 58t Para-aminosalicy'ic acid, 36t Recurrent benign lymphocytic meningitis, l Parainfluenza virus, 2, 97t Respiratory syncytial virus (RSV), 9Zt Paraneoplastic syndrome, 7 Respiratory viruses, 97t Retapamulin, 11t Parasitic infections, 74-75 Parasitic meningitis, 4 Retinitis, 100 Rhinovirus, 15 Paromomycin, for amebiasis, 75 Ricin toxin, bioterrorism and, 57t Parvovirus B19, 2 Ricketfsio spp., 27, 28t,67 Pasteurella spp., 9t, 12 Rickettsial infections, 6tt, 67 Pelvic inflammatory disease (PID), 45, 47, Q92 Rifabutin, for tuberculosis, 36t Penicillins Rifampin allergr to, Q96 for active tuberculosis, 37t for brain abscesses, 6t for brucellosis. 68 for C. perfringens NFl, Q20 for latent tuberculosis, Q78 for cellulitis, 11t for osteomyelitis, 52 for erysipelas, 11t for tuberculosis, 361, Q23 for MSSA. 85 Rifamycin, for travelers' diarrhea, 65, 65t for syphilis, 50t Rifapentine, for tuberculosis, 36t Peptostreptococcus, 13 Rifaximin. 65. 65t. Q105 Peramivir, for influenza infections, 98 Rilpivirine, for HIV infection, 96t Perinephric abscesses, 27 Ritonavir, for HIV infection, 96t Peripherally inserted central catheters (PICCs), Q1 Krtuxrmao, /, 561, /6t Piperacillin-tazobactam, 11, 111, 30 31 Rocky Mountain spotted fever (RMSF) ,27,27f Plague, 571, 58, 59, 59f Roseolovirus, manifestations of, 99t Plasmapheresis, 7 Rotavirus, 2, 74 Plasmodium spp., 62, 621,63t Rubella, encephalitis and, 2 Plazomicin, 104, 1051 Pleocytosis, 1 5 Pleural effusion, 34t Salmonella diarrhea, 69t, 7l Pneumocg stis jirou ecii, 9 2t, 9 4 Sqlmonella enterice, 62- 65 Pneumocystis pneumonia, 78 Schistosomo spp., meningitis caused by, 4 Pneumonia, 14 21. Q3, Q68. See olso community-acquired pneumonia; Selective IgA deficiency (SIgAD), 55, 55t health care-associated pneumonia; hospital-acquired Severe acute respiratory syndrome (SARS), 61t pneumonia; ventilator-associated pneumonia Sexual practice counseling, Q93 Pneumonia Severity Index (PSI), 19 Sexually transmitted infections (STIs), 44-51, Q2, Q60 Podofilox, for genital warts, 51 Shigella diarrhea, 69t, 7 O -7 7 Poliovirus, encephalitis and, 2 Shingles, acyclovir for, 100, Q71 Polymlxin E, activity of, 104 Sinecatechins, for genital warts, 51 Porphyromonos spp., 12 Sirolimus (rapamycin), z6t Posaconazole, 44,79 Skin and soft tissue infections (SSTIs), 8 14, 11t Post-Lyme disease syndrome, 24, Q6 Skin pathogens, risk factors, 9t Posttransplant infections, 76 79,76t, Q26, Q41 Smallpox (Variola), 57-59, 59f Posttransplant lymphoproliferative disorder (PTLD), Q76 Smallpox, bioterrorism and, 57t Posttreatment Lyme disease syndrome (PTLDS), Q6 Soft tissue infections, 8 14 Pott puffy tumors, 5 Southern tick-associated rash illness (STARI), 25-26 Powassan virus, 27 Spinal epidural abscesses, 5-6 Powassan virus encephalitis,T, Q42 Sporothrix schenckii, 9t Prednisone, immunosuppression by, 7 6t Sporotrichosis, 43 Pre-exposure prophyalxis (PrEP), HIV Q29, Q102 Spotted fever rickettsioses, 261, 27 Pregnant patients Sputum cultures, 18 cystitis in, Q100 St Louis encephalitis, 2, 7 with HIV infection, 96-97 Staphylococcal enterotoxin B, 57t Pretomanid, for tuberculosis, 36t Staphglococcus oureus. See olso methicillin resistant S. oureus (MRSA); Preuotella spp., 13 methicillin-sensitive S. oureus (MSSA) Primaquine, 63t,64t antibiotic resistant, 103 Primary effusion lymphoma, 94 bacteremia, 85-86 Progressive multifocal leukoencephalopathy, 94 CAP and, 15 Prostatitis, 27, 3l-32, Q22 osteomyelitis and, 52-53 Pseudomones ae ruginosa spinal epidural abscesses and, 5-6 antibiotic resistant, 103-104 toxic shock syndrome and, 14 CAP and, 20 UTIs and, 28 folliculitis caused by, 11, 12 Staphylococcus spp., 5, 13

o management of infections, e4, e40, e59 Obiltoxaximab, for anthrax, 5gt risk factors associated with. 9t Ofloxacin, for travelers' diarrhea, 65t vertebral osteomyelitis and, 53 Omadacycline, 12, 104, 1051 Psittacosis, bioterrorism and, 57t Oritavancin, for MRSA, 12 Purpura fulminans, 27 Oseltamivir, for influenza, 9g, e46 Pyelonephritis, 27, 30-31, Q19 Osteomyelitis, 51-53 Pyrazinamide, 36t, 371, Q23 biopsy of, Q91 Pyridoxine. for LTBI, 35 diabetic foot infections and, 52-53, e79 Pyuria, diagnosis of, 28-29 diagnosis of, S1-S2, Q34 imaging in,52f, Q79 o manifestations of, 51 Q fever, 57t,67t MSSA-related, Q87 Quinine sulfate, 64t treatment of, 52, Q28 Quinolones, adverse effects of, 20 vertebral,53, Q28, Q34 R Otitis media, 5 Outpatient parenteral antibiotic therapy (OPAT), 104 Rabies, clinical clues, 61t Ovarian teratomas, 7 Radiculopathy, Lyme disease and, 23 Oxacillin, for S. oureus infections, 14 Raltegravir, 88, 96t Ramsay Hunt syndrome, 101, 101f, QB1 P Raxibacumab, for anthrax, 58t Para-aminosalicy'ic acid, 36t Recurrent benign lymphocytic meningitis, l Parainfluenza virus, 2, 97t Respiratory syncytial virus (RSV), 9Zt Paraneoplastic syndrome, 7 Respiratory viruses, 97t Retapamulin, 11t Parasitic infections, 74-75 Parasitic meningitis, 4 Retinitis, 100 Rhinovirus, 15 Paromomycin, for amebiasis, 75 Ricin toxin, bioterrorism and, 57t Parvovirus B19, 2 Ricketfsio spp., 27, 28t,67 Pasteurella spp., 9t, 12 Rickettsial infections, 6tt, 67 Pelvic inflammatory disease (PID), 45, 47, Q92 Rifabutin, for tuberculosis, 36t Penicillins Rifampin allergr to, Q96 for active tuberculosis, 37t for brain abscesses, 6t for brucellosis. 68 for C. perfringens NFl, Q20 for latent tuberculosis, Q78 for cellulitis, 11t for osteomyelitis, 52 for erysipelas, 11t for tuberculosis, 361, Q23 for MSSA. 85 Rifamycin, for travelers' diarrhea, 65, 65t for syphilis, 50t Rifapentine, for tuberculosis, 36t Peptostreptococcus, 13 Rifaximin. 65. 65t. Q105 Peramivir, for influenza infections, 98 Rilpivirine, for HIV infection, 96t Perinephric abscesses, 27 Ritonavir, for HIV infection, 96t Peripherally inserted central catheters (PICCs), Q1 Krtuxrmao, /, 561, /6t Piperacillin-tazobactam, 11, 111, 30 31 Rocky Mountain spotted fever (RMSF) ,27,27f Plague, 571, 58, 59, 59f Roseolovirus, manifestations of, 99t Plasmapheresis, 7 Rotavirus, 2, 74 Plasmodium spp., 62, 621,63t Rubella, encephalitis and, 2 Plazomicin, 104, 1051 Pleocytosis, 1 5 Pleural effusion, 34t Salmonella diarrhea, 69t, 7l Pneumocg stis jirou ecii, 9 2t, 9 4 Sqlmonella enterice, 62- 65 Pneumocystis pneumonia, 78 Schistosomo spp., meningitis caused by, 4 Pneumonia, 14 21. Q3, Q68. See olso community-acquired pneumonia; Selective IgA deficiency (SIgAD), 55, 55t health care-associated pneumonia; hospital-acquired Severe acute respiratory syndrome (SARS), 61t pneumonia; ventilator-associated pneumonia Sexual practice counseling, Q93 Pneumonia Severity Index (PSI), 19 Sexually transmitted infections (STIs), 44-51, Q2, Q60 Podofilox, for genital warts, 51 Shigella diarrhea, 69t, 7 O -7 7 Poliovirus, encephalitis and, 2 Shingles, acyclovir for, 100, Q71 Polymlxin E, activity of, 104 Sinecatechins, for genital warts, 51 Porphyromonos spp., 12 Sirolimus (rapamycin), z6t Posaconazole, 44,79 Skin and soft tissue infections (SSTIs), 8 14, 11t Post-Lyme disease syndrome, 24, Q6 Skin pathogens, risk factors, 9t Posttransplant infections, 76 79,76t, Q26, Q41 Smallpox (Variola), 57-59, 59f Posttransplant lymphoproliferative disorder (PTLD), Q76 Smallpox, bioterrorism and, 57t Posttreatment Lyme disease syndrome (PTLDS), Q6 Soft tissue infections, 8 14 Pott puffy tumors, 5 Southern tick-associated rash illness (STARI), 25-26 Powassan virus, 27 Spinal epidural abscesses, 5-6 Powassan virus encephalitis,T, Q42 Sporothrix schenckii, 9t Prednisone, immunosuppression by, 7 6t Sporotrichosis, 43 Pre-exposure prophyalxis (PrEP), HIV Q29, Q102 Spotted fever rickettsioses, 261, 27 Pregnant patients Sputum cultures, 18 cystitis in, Q100 St Louis encephalitis, 2, 7 with HIV infection, 96-97 Staphylococcal enterotoxin B, 57t Pretomanid, for tuberculosis, 36t Staphglococcus oureus. See olso methicillin resistant S. oureus (MRSA); Preuotella spp., 13 methicillin-sensitive S. oureus (MSSA) Primaquine, 63t,64t antibiotic resistant, 103 Primary effusion lymphoma, 94 bacteremia, 85-86 Progressive multifocal leukoencephalopathy, 94 CAP and, 15 Prostatitis, 27, 3l-32, Q22 osteomyelitis and, 52-53 Pseudomones ae ruginosa spinal epidural abscesses and, 5-6 antibiotic resistant, 103-104 toxic shock syndrome and, 14 CAP and, 20 UTIs and, 28 folliculitis caused by, 11, 12 Staphylococcus spp., 5, 13 199

lndex Status epilepticus, autoimmune, 7 u Streptobacillus moniliformis. 9t Undulant fever, Q65 Streptococcus spp. Urethritis, 46t,47 human bites infected bY, 13 Urinary tract infections (UTIs), 27-32 S. agalactiae,2S catheter-associated, 27, 80-82, 82t' Ql8' Q82 S. maltophilia,TO4 multidrug-resistant, Q53 S. pneumoniae,2,15,78 prevention of, Q82 S. pyogenes, lO ll, 14, 16, l7t recurrent, 31, Q36 SSTIs caused by, 8, 8f Uveitis, syphilis and, 49 Streptomycin, 361, 58t UveomeningoencePhalitis, 4 Strongyloides, posttransPlant, 78 U Subdural abscesses, 5 Vaccinations Subdural empyema, 5 after anthrax exPosure, Q25 Sulfonamides,6t CVID and, Q27 Surgical site infections (SSIs), 82-84,831, Q31 hepatitis A, Q56 Syndrome of inappropriate secretion of antidiuretic hormone (SIADH),4 in HIV patients, Q24 Syphilis, 2,48-s0, 491 sot, Q12, Q60, Q108 in transplant recipients, 79t pre-travel, Q56 Systemic lupus erythematosus (SLE), 4 travel and, 60t I typhoid, Qs6 Tacrolimus, immunosuppression by, 7 6t Valacycloviq 101, Q44 Taenia solium, meningitis caused by,4 Valganciclovir, T9 , 80, 7O2 Tafenoquine, 631, 64t Vancomycin Tecovirimat, for smallpox, 58t for bacterial meningitis, Q48 Tedizolid, for MRSA skin infections, 12 for brain abscesses, 6t Telavancin, for furuncle, 1lt for C. dfficile infection, Q10, Q61 Tenofovir disproxil fumarate (TDF), 88, 92,95,961, Q29 for CAP, 17t Tenofovir-emtricitabine, Q1 02 for diabetic foot infections, 14 Tenovir alafenamide (TAF), 92, 96t for furuncle, carbuncle or abscess, l.Lt Thoracentesis, 19, Q9 for HAP and VAP, 86 Thrombocytopenia, 72 for infectious diarrhea, 69t,73 Tick bites, 2 for meningitis, Q85 Tick-borne diseases, 21-27, 28t, 68 monitoring therapy with, Q89 Tick-borne encephalitis, 611, 68 for MRSA, 9, 20, 85 Ticks, life stages ol 22f for NFl 11t Tinidazole, 7Ot,74 for skin infections, 11 Tourniquet test, 66f for VAB Q4 Toxic shock syndrome (TSS), 14, 15t for vertebral osteomyelitis, Q28 Toxoplosma gondii, 7 8, 9 4 Varicella-zoster virus (VZV) Toxoplasmosis, HIV and, 92t, 94f acyclovir for, Q71 Transfusions, babesiosis transmission and, Q83 CAP and, 16 Transplant donors, testing of, 76 encephalitis caused by, 7 Transplant recipients features ol 100-101 antirejection drugs in, 75 76 folliculitis caused by, 11 infections in.75-80 manifestations of 99t, 1o0f prevention of infections in, 79 -8O, 79t meningitis caused by, 1 timeline of common infections, 76-78,76t,77f Ramsay Hunt syndrome, Q81 Travel medicine, 60-68, 601. 611, Q56, QlOs transmission of, 99-100, Q45 Traveler's diarrhea, 611, 65t Ventilator-associated pneumonia (VAP), 86-87, Treponema pqllidum meningitis, 2 Q4 Trichloroacetic acid, 51 Ventriculitis, health care-associated, Q85 Trimethoprim-sulfamethoxazole Vertebral osteomyelitis, 53, Q28, Q34 for acute bacterial prostatitis, 32 Vibrio dianhea,T2 for acute pyelonephritis, 30-31 Vibrio parahaemolgticus, 9t, 69t, 72 for bite wounds, 13 Vibrio vulnificus, 9t, 11, Q13 for diabetic foot infections, 14 Viral encephalitis, 7, 57t for furuncle, carbuncle or abscess, 11t Viral gastroeteritis, 74 for infectious diarrhea, 70t, 71 Viral hemorrhagic fever, 57t,60 posttransplant infection prophylaxis using, 79 Viral hepatitis, clinical clues, 61t prophylaxis, in AIDS patient, Q1O4 Viral infections, vaccine preventable, 102 - 103 for recurrent UTIs, 31 Viral meningitis,l-2 for UTIs, 29-30 Viral resistance testing, 95-96 Trypanosomo, posttransplant infections, 78 Vogt-Koyanagi-Harada qmdrome, 4 Tuberculin skin tests, interpretation of, 33t, Q51 Voriconazole, 4t,79 Tuberculosis (TB), 32 39 chest radiograph, 34t w disseminated, Q101 West Nile virus (WNV), 2,7,Q75 HIV and, 92t,93-94, Q69 Western equine encephalitis, 7 latent infection, 33-34, Q78 V management of 36t Yellow fever flavivirus, 68 prevention of, 38 Yersinia diarrhea, 69t, 7 2 risk factors, 32t Yersinia enterocolitica, 7 2 screening for, Q74 Yersiniapestis, 58, 59 spinal abscesses and, 6 treatment of active disease, 371, Q23 I Tularemia, 571, 58, 59 60 Zanamivir, for idluerza infections, 98 Tumor necrosis factor inhibitors, 37-38, 56t Zidovudine, for HIV infection, 96t Typhoid (enteric) fever, 611. 62-65,6Sf, QS6 Zika virus, 61t,66-67

Status epilepticus, autoimmune, 7 u Streptobacillus moniliformis. 9t Undulant fever, Q65 Streptococcus spp. Urethritis, 46t,47 human bites infected bY, 13 Urinary tract infections (UTIs), 27-32 S. agalactiae,2S catheter-associated, 27, 80-82, 82t' Ql8' Q82 S. maltophilia,TO4 multidrug-resistant, Q53 S. pneumoniae,2,15,78 prevention of, Q82 S. pyogenes, lO ll, 14, 16, l7t recurrent, 31, Q36 SSTIs caused by, 8, 8f Uveitis, syphilis and, 49 Streptomycin, 361, 58t UveomeningoencePhalitis, 4 Strongyloides, posttransPlant, 78 U Subdural abscesses, 5 Vaccinations Subdural empyema, 5 after anthrax exPosure, Q25 Sulfonamides,6t CVID and, Q27 Surgical site infections (SSIs), 82-84,831, Q31 hepatitis A, Q56 Syndrome of inappropriate secretion of antidiuretic hormone (SIADH),4 in HIV patients, Q24 Syphilis, 2,48-s0, 491 sot, Q12, Q60, Q108 in transplant recipients, 79t pre-travel, Q56 Systemic lupus erythematosus (SLE), 4 travel and, 60t I typhoid, Qs6 Tacrolimus, immunosuppression by, 7 6t Valacycloviq 101, Q44 Taenia solium, meningitis caused by,4 Valganciclovir, T9 , 80, 7O2 Tafenoquine, 631, 64t Vancomycin Tecovirimat, for smallpox, 58t for bacterial meningitis, Q48 Tedizolid, for MRSA skin infections, 12 for brain abscesses, 6t Telavancin, for furuncle, 1lt for C. dfficile infection, Q10, Q61 Tenofovir disproxil fumarate (TDF), 88, 92,95,961, Q29 for CAP, 17t Tenofovir-emtricitabine, Q1 02 for diabetic foot infections, 14 Tenovir alafenamide (TAF), 92, 96t for furuncle, carbuncle or abscess, l.Lt Thoracentesis, 19, Q9 for HAP and VAP, 86 Thrombocytopenia, 72 for infectious diarrhea, 69t,73 Tick bites, 2 for meningitis, Q85 Tick-borne diseases, 21-27, 28t, 68 monitoring therapy with, Q89 Tick-borne encephalitis, 611, 68 for MRSA, 9, 20, 85 Ticks, life stages ol 22f for NFl 11t Tinidazole, 7Ot,74 for skin infections, 11 Tourniquet test, 66f for VAB Q4 Toxic shock syndrome (TSS), 14, 15t for vertebral osteomyelitis, Q28 Toxoplosma gondii, 7 8, 9 4 Varicella-zoster virus (VZV) Toxoplasmosis, HIV and, 92t, 94f acyclovir for, Q71 Transfusions, babesiosis transmission and, Q83 CAP and, 16 Transplant donors, testing of, 76 encephalitis caused by, 7 Transplant recipients features ol 100-101 antirejection drugs in, 75 76 folliculitis caused by, 11 infections in.75-80 manifestations of 99t, 1o0f prevention of infections in, 79 -8O, 79t meningitis caused by, 1 timeline of common infections, 76-78,76t,77f Ramsay Hunt syndrome, Q81 Travel medicine, 60-68, 601. 611, Q56, QlOs transmission of, 99-100, Q45 Traveler's diarrhea, 611, 65t Ventilator-associated pneumonia (VAP), 86-87, Treponema pqllidum meningitis, 2 Q4 Trichloroacetic acid, 51 Ventriculitis, health care-associated, Q85 Trimethoprim-sulfamethoxazole Vertebral osteomyelitis, 53, Q28, Q34 for acute bacterial prostatitis, 32 Vibrio dianhea,T2 for acute pyelonephritis, 30-31 Vibrio parahaemolgticus, 9t, 69t, 72 for bite wounds, 13 Vibrio vulnificus, 9t, 11, Q13 for diabetic foot infections, 14 Viral encephalitis, 7, 57t for furuncle, carbuncle or abscess, 11t Viral gastroeteritis, 74 for infectious diarrhea, 70t, 71 Viral hemorrhagic fever, 57t,60 posttransplant infection prophylaxis using, 79 Viral hepatitis, clinical clues, 61t prophylaxis, in AIDS patient, Q1O4 Viral infections, vaccine preventable, 102 - 103 for recurrent UTIs, 31 Viral meningitis,l-2 for UTIs, 29-30 Viral resistance testing, 95-96 Trypanosomo, posttransplant infections, 78 Vogt-Koyanagi-Harada qmdrome, 4 Tuberculin skin tests, interpretation of, 33t, Q51 Voriconazole, 4t,79 Tuberculosis (TB), 32 39 chest radiograph, 34t w disseminated, Q101 West Nile virus (WNV), 2,7,Q75 HIV and, 92t,93-94, Q69 Western equine encephalitis, 7 latent infection, 33-34, Q78 V management of 36t Yellow fever flavivirus, 68 prevention of, 38 Yersinia diarrhea, 69t, 7 2 risk factors, 32t Yersinia enterocolitica, 7 2 screening for, Q74 Yersiniapestis, 58, 59 spinal abscesses and, 6 treatment of active disease, 371, Q23 I Tularemia, 571, 58, 59 60 Zanamivir, for idluerza infections, 98 Tumor necrosis factor inhibitors, 37-38, 56t Zidovudine, for HIV infection, 96t Typhoid (enteric) fever, 611. 62-65,6Sf, QS6 Zika virus, 61t,66-67 200