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Gastroenterology and Hepatology lnflammatory Bowel Disease Diagnosis The two most common IBDs are Crohn disease and ulcerative colitis, both of which cause macroscopic inflammation. Microscopic colitis does not cause significant macroscopic abnormalities. STUDY TABLI: Differentiating Ulcerative Colitis {rom Crohn Disease Ulcerative Colitis Crohn Disease Mucosal edema, erythema, and loss of the vascular pattern; Linear, stellate, or serpiginous ulcerations with "skip" areas of a nd bleed n g g ra nu la rity; friabi I ity; u lceration; i inflammation involving entire Gl tract Altered crypt architecture with shortened, branched crypts and Granulomas are characteristic but are often not found. Transmural crypt abscesses involvement. Diarrhea (prominent), tenesmus, u rgency hematochezia, weight Abdominal pain (prominent), diarrhea, inflammatory masses, loss, and fever fevel weight loss, intestinal strictures and fistula Smoking al leviates symptoms Smoking is a risk factor for disease The most common extraintestinal manifestations are arthralgia, back pain (indicating anlcylosing spondylitis or sacroiliitis), and oral aphthous ulcers. Eye redness, pain, and swelling may result from uveitis, iritis, or episcleritis. Skin manifestations include pyoderma gangrenosum and ery.thema nodosum. Liver involvement suggests PSC. Testing Colonoscopy and biopsy confirm the diagnosis. Stool studies are indicated for Shigello , Salmonella, Campylobacter, Escherichia coli O757:H7 , ova and parasites, and C. dfficile toxin, especially if symptoms are acute. Fecal calprotectin should be considered to help differentiate between IBD and IBS. DOil'T BE TRICKED o Do not perform a barium enema examination in patients with moderate to severe ulcerative colitis because this procedure may precipitate toxic megacolon. o In patients with Crohn disease and cystitis, consider the possibility of enterovesical fistula.

Testing Colonoscopy and biopsy confirm the diagnosis. Stool studies are indicated for Shigello , Salmonella, Campylobacter, Escherichia coli O757:H7 , ova and parasites, and C. dfficile toxin, especially if symptoms are acute. Fecal calprotectin should be considered to help differentiate between IBD and IBS. DOil'T BE TRICKED o Do not perform a barium enema examination in patients with moderate to severe ulcerative colitis because this procedure may precipitate toxic megacolon. o In patients with Crohn disease and cystitis, consider the possibility of enterovesical fistula. Treatment Patients with IBD should receive seasonal influenza and both pneumococcal vaccines. Ideally, pneumococcal vaccination should occur before beginning immunosuppressive therapy. Treatment of Crohn disease and ulcerative colitis is divided into active and maintenance strategies. Specific treatment choices depend on the type, extent, and severity ofthe disease. STUDY TABLE: Medical Treatment of lnflammatory Sowel Disease DiseaseActivity UlcerativeColitis Crohn Disease Mild Oral and topical 5-ASAsu Sulfasalazine for colitis" Steroid suppository and enemab Budesonide for ileocolonic diseaseb Multimatrix budesonide Moderate Oral and topical 5-ASAs" Oral and intravenous glucocorticoidsb Azathioprine/6-MP' Budesonide for ileocolonic diseaseb Multimatrix budesonide and oral glucocorticoidsb Azathioprine/6-MP' Biologic agents (infliximab, adalimumab, golimumab, Methotrexate' vedolizumab, ustekinu mab)" Biologic agents (infliximab, adalimumab, certolizumab, Tofacitinibu vedolizumab, natalizumab, ustekinumab)u (Continued on the next page) 95

General lnternal Medicine Diagnosis Look for alcohol use disorder in patients with select conditions, including repeated trauma, hypertension, AF, HF, pancreatitis, alcoholic hepatitis, and cirrhosis. Laboratory clues such as an elevated MCV, y glutamyltransferase level, and AST ALI ratio >2 are suglestive but not diagnostic. STUDY TABLE! Categories and Patterns of Alcohol Use Categories Patterns At-risk drinking Men: >14 drinks per week or >4 drinks per occasion Women and adults age 265 y: >7 drinks per week or >3 drinks per occasion Alcohol use disorder Alcohol use leading to significant impairment or distress, as manifested by multiple psychosocial behavioral, or physiologic features In patients undergoing alcohol withdrawal, look for: o tremor, anxiety, diaphoresis, and palpitations 6 to 36 hours after the last drink r visual, auditory, and tactile hallucinations 12 to 48 hours after the last drink . generalized tonic clonic seizure within 6 to 24 hours after the last drink o delirium tremens (hallucinations, delirium, agitation, fever, palpitations, and hypertension) 24 to 48 hours after the last drink DON'T BE TRICKED o Screening for alcohol use disorder begins with quanti$ring the amount of alcohol consumed, not CAGE or AUDIT-C questions. . Multiple seizures (>1) are not consistent with alcohol withdrawal syndrome and should prompt an evaluation for another disorder. Treatment For management of alcohol use disorder, the USPSTF recommends referral for specialty treatment. For at risk drinking, brief behavioral counseling (such as the five A s and the five Rs, Iisted previously) may be usef'ul. Use naltrexone to prevent relapse of alcohol abuse and dependence. It can be used in patients who are actively drinking. Naltrexone is contraindicated in patients receiving or withdrawing fiom any opioid and in those with Iiver failure or hepatitis. Acamprosate enhances abstinence but is contraindicated in kidney disease. Disulfiram is a second line treatment that causes the accumulation of acetaldehyde if alcohol is consumed, resulting in flushing, headache, emesis, and the need to avoid all additional alcohol containing items.

Use naltrexone to prevent relapse of alcohol abuse and dependence. It can be used in patients who are actively drinking. Naltrexone is contraindicated in patients receiving or withdrawing fiom any opioid and in those with Iiver failure or hepatitis. Acamprosate enhances abstinence but is contraindicated in kidney disease. Disulfiram is a second line treatment that causes the accumulation of acetaldehyde if alcohol is consumed, resulting in flushing, headache, emesis, and the need to avoid all additional alcohol containing items. Hospitalize patients with moderate to severe alcohol withdrawal or another compelling need fbr hospitalization. Benzodiazepines are indicated for hospitalized patients: o with previous alcohol related seizures or delirium tremens o with significant withdrawal symptoms . who are pregnant o with acute medical or surgical illnesses Long-acting benzodiazepines are typically preflerred. Use a symptom triggered regimen to treat alcohol withdrawal (for example, Clinical Institute Withdrawal Assessment fbr Alcohol, Revised [CIWA Ar]). Adjunctive therapy with P-blockers and clonidine may help control tachycardia and hypertension but are not used as monotherapy. 137

lnfectious Disease Diagnosis UTIs (either cystitis or pyelonephritis) are classified as uncomplicated or complicated. Uncomplicated UTI is acute cystitis and pyelonephritis occurring in healthy, nonpregnant women with no history of urinary tract abnormalities. Complicated UTIs occur: . in men and pregnant women o in the presence of foreign bodies (catheters, calculi) o in kidney disease o in immunocompromised hosts o in obstruction and other causes of urinary retention o with recent antibiotic use Designating an infection as complicated influences the choice and duration of antimicrobial therapy and extent of investigation. DOil'T BETRICKED . Age alone does not define a complicated versus uncomplicated infection. Testing Patients with uncomplicated cystitis do not require a urine culture but can be diagnosed with either: . urine dipstick positive for leukocyte esterase and nitrites o >10 WBCs/pL and bacteriuria Obtain a urine culture for: r suspected pyelonephritis r complicated UTI o recurrent UTI . recent antibiotic treatment o health care-associated UTI Treatment For women with s5rmptoms of uncomplicated cystitis, prescribing antibiotics over the telephone without seeing the patient or obtaining a urina$sis is acceptable. For empiric treatment of uncomplicated cystitis in nonpregnant women, select one of the following: . 3 days of oral trimethoprim-sulfamethoxazole . 5 days of oral nitrofurantoin . single dose of fosfomycin In patients at high risk for complicated UTI, obtain a urine culture and initiate empiric treatment for 7 to 10 days with a fluoroquinolone. For pregnant women, choose 7 days of empiric therapy with amoxicillin-clavulanate, cefpodoxime, or cefixime. Obtain a urine culture after treatment. 232

lnfectioug Disease For recurrent uncomplicated UTIs, select one or more of the following: o postcoital antibiotic prophylaxis, particularly if UTIs are temporally associated with coitus e continuous antibioticprophylaxis o self-initiated therapy for frequent recurrent episodes DOX'T BE TilCKED o Trimethoprim-sulfamethoxazole should not be used if it was taken in the preceding 3 months. . Do not schedule a routine follow-up urinalysis or culture after treatment for nonpregnant women with uncomplicated cystitis. Pyelonephritis Diagnosis Selonephritis is associated with the abrupt onset of fever, chills, nausea, and flank or abdominal pain. Hypotension and septic shockmayoccur. Testing Presence ofbacteriuria and pyuria is the gold standard for the diagnosis ofpyelonephritis. Obtain urine cultures for all patients and blood cultures for significanfly ill patients. Imaging studies are indicated only for patients in whom an alternative diagnosis or a urologic complication is suspected. Treatment For patients with uncomplicated infection who are able to tolerate oral therapy, select ciprofloxacin for 7 days or levofloxacin for 5 days. Treat complicated infection for 14 days. Inpatient parenteral antimicrobial options include a fluoroquinolone, extended-spectrum cephalosporins (ceftriaxone or cefepime) or extended-spectrum penicillins (piperacillin-tazobactam), or a carbapenem (meropenem, imipenem, or ertapenem). Obtain ultrasonogmphy or CT for persistent fetrer 272 hours, for persistent bacteremia, or to ev"aluate for complications of pyelonephritis (e.g., perinephric abscess). DO]I'T BETNrcKED o Follow-up urine cultures are indicated only in pregnent women. Tuberculosis Screening The IGRA is the initial screening study for latent TB infection. A TST is the alternative test if IGRA is not feasible or available. 233

lnfectious Disease DOil'T BETRICKED o Interpret a positive TST in a patient with a history of bacillus Calmette-Gudrin vaccination the same as in a person without a history of this vaccination. Diagnosis Know the different TST threshold measurements for TB infection. STUtrY TABLE: lnterpretation of Tuberculin Skin Test Results Criteria for Tuberculin Positivity by Risk Group >5 mm lnduration 210 mm lnduration )15 mm lnduration Persons who are HIV positive Recent (<5 y) arrivals from high-prevalence All others with no risk countries factors forTB Recent contacts of persons with active TB Persons who inject drugs Persons with fibrotic changes on chest x-ray consistent with old TB Residents or employees of high-risk congregate settings: prisons and jails, nursing homes and other Patients with organ transplants and other long-term facilities for older adults, hospitals and immunosuppressive conditions (receiving other health care facilities, residentialfacilities for the equivalent of >1 5 mg/d of prednisone patients with AIDS, homeless shelters for >4 weeks) Mycobacteriology laboratory personnel; persons with clinical conditions that put them at high risk {or active disease; children aged <4 years orthose exposed to adults in high-risk categories tatent TB infection is defined by a positive TST or IGRA in the absence of any systemic manifestation of active infection and a normal chest x-ray. Pulmonary TB accounts for7O"/,, of active disease cases and is characterized by constitutional or pulmonary signs or symptoms that are often insidious and may include: o cough >3 weeks, chest pain, and hemoptysis o fever, chills, and night sweats o weight loss

tatent TB infection is defined by a positive TST or IGRA in the absence of any systemic manifestation of active infection and a normal chest x-ray. Pulmonary TB accounts for7O"/,, of active disease cases and is characterized by constitutional or pulmonary signs or symptoms that are often insidious and may include: o cough >3 weeks, chest pain, and hemoptysis o fever, chills, and night sweats o weight loss Testing Obtain chest x-ray and acid-fast bacilli smears and cultures on three sputum specimens in patients with suspected active TB. Sputum or tissue culture is the gold standard for diagnosis, but results may be delayed for weeks. Stains for acid-fast bacilli are rapid but neither sensitive nor specific. Obtain NAAT of sputum when acid-fast bacilli smear is positive to exclude nontuberculous mycobacteria or to conflrm Mycobacterium tuberculosis in patients with high likelihood of disease but negative sputum smears. DO]II,T BE TRICKED . A negative NAAT cannot exclude pulmonary TB. o Obtain cultures even if NAAT is positive to determine drug susceptibility 234

lnfectious Disease STUtrY TABLE: Chest X-ray Patterns for Pulmonary TB Syndrome Pattern Reactivation TB lnfiltrates in the apical-posterior segments of the upper lung and superior segments o{ the lower lobe Primary progressive TB Hilar lymphadenopathy or infiltrates in any part of the lung CavitaryTB Cavities without air-fluid levels; may be associated with either primary progressive or reactivation TB lm munocompromised patients Typical or absent radiologic findings are common MiliaryTB Characteristic "millet seed" appearance (uniform reticulonodular infiltrate) CT scans may identi$z abnormalities not yet visible on chest x ray. Pulmonary Iubel(ulosis: Upper lobe infiltrates and cavitation consistent with pulmonary IB. For suspected pleural TB, perform thoracentesis for analysis and culture (positive in only 50% ofcases). Ifnegative, perform pleu- Miliary luberculosis: Chest x-ray reveals the bilateral presence of innumerable ral biopsy. Pleural fluid adenosine deaminase levels are helpful in 1'to 3-mm nodules, predominantly seen within the lower lung fields, typical of the evaluation of suspected pleural TB in patients with a negative miliary TB. culture and pleural biopsy. TB meningitis is associated with CSF showing lymphocytic pleocltosis with elevated protein and decreased glucose levels. NAAT of the CSF is highly specific. DON'T BE TRICKED . In persons not already known to be HIV positive, test for HIV infection. Treatment For latent TB: For patients without HIV select any of the following: . 3 months of isoniazid plus rifapentine given once weekly o 3 months of isoniazid plus rifampin given daily . 4 months of rifampin given daily 235

lnfectious Disease In patients with HIV the first and second regimens listed are acceptable if no drug-drug interactions with HIV medications have been identified. For active TB, the core first-line agents are isoniazid, rifampin, pyrazinamide, and ethambutol. These agents are administered daily for 2 months, and then isoniazid and rifampin are continued daily for either 4 or 7 months. The three criteria that establishes a patient as no longer infectious: . adequate TB treatment >2 weeks o improvement of symptoms . three consecutive negative sputum smears DO]I'T BE TRICKED r If ethambutol is used, visual acuity and color vision testing is recommended. . Rifampin is contraindicated or must be used with caution when administered with protease inhibitors and nonnucleoside reverse transcriptase inhibitors; do not administerwith saquinavir/ritonavir. TESTYOURSEIF A 4O-year-old asymptomatic female hospital employee has a 10 mm TST reaction following routine screening. The employee was born in India and has lived in the United States for 1O years. She was vaccinated with bacillus Calmette-Gu€rin as a child. Her chest x-ray is normal. ANSWER: For diagnosis, choose latent TB. Candida lnfections Diagnosis Mucocutaneous candidiasis may present as an erythematous intertriginous rash with satellite lesions. Oral candidiasis appears as adherent, painless white plaques on the tongue and buccal mucosa. Local invasion is most apparent in the esophagus and tends to occur in persons with reduced cell-mediated immunity (HIV) or severe neutropenia. Invasive candidiasis includes candidemia, focal organ involvement, and disseminated candidiasis, with candidemia being the most common. Candidemia occurs most frequently in the presence of an intravascular catheter. In suspected disseminated disease, white exudates may be seen in the retina on ophthalmoscopic examination, and painless skin papules or pustules on an ery.thematous base may be present on the skin. Diagnosis is made by positive culture from the blood or a normally sterile body fluid or site. DOil'T BE TRICKED . When Condido is isolated from the sputum, it usually reflects contamination from the oral mucosa. . Candidain a blood culture is never a contaminant.

In suspected disseminated disease, white exudates may be seen in the retina on ophthalmoscopic examination, and painless skin papules or pustules on an ery.thematous base may be present on the skin. Diagnosis is made by positive culture from the blood or a normally sterile body fluid or site. DOil'T BE TRICKED . When Condido is isolated from the sputum, it usually reflects contamination from the oral mucosa. . Candidain a blood culture is never a contaminant. Treatment Otal Candida: Acute oral candidiasis presenting as white plaques that are painful An echinocandin (anidulafungin, caspofungin, or micafungin) and in a patient with HIV infection. intravascular device removal are recommended as initial treatment for most patients with candidemia. Patients with CNS and eye infec tions should be treated with amphotericin B or an azole. 236

lnfectious Disease Fluconazole is effective in preventing Candida infections in neutropenic oncologz patients, but it has limited effectiveness for preventing other fungal infections. DOil'T BE TRICKED . Treatment is not indicatedfor Candidsin the sputum of patients receiving mechanical ventilation. . Do not treat asymptomatic candiduria except in neutropenic patients or those undergoing invasive urologic procedures. Aspergillosis Diagnosis STU pY TABLE : Pulmonary Aspergillosis Syndromes Condition Characteristics Allergic bronchopulmonary aspergillosis Usually occurs in the setting of asthma or CF Other findings are a positive skin test, elevated lgE, and eosinophilia Presents as difficult-to-control asthma and recurrent pulmonary infiltrates Aspergilloma (fungus ball) Occurs in preexisting pulmonary cavities or cysts, or in areas of devitalized lung Symptoms are cough, hemoptysis, dyspnea, weight loss, fever, and chest pain lnvasive pulmonary aspergillosis Occurs most commonly in immunocompromised hosts (neutropenia or hematopoietic stem cell transplant recipients) CT scan may show the "halo sign," a target lesion with surrounding ground-glass attenuation (hemorrhage) Symptoms are cough, fever, hemoptysis, pleuritic chest pain Neutropenic patients and organ transplant recipients are at increased risk for developing Aspergillus infections. Testing Blood cultures are rarely positive. The initial test for suspected invasive aspergillosis is either serum galactomannan assay or, if negative, bronchoalveolar lavage with PCR test- ing followed by tissue biopsy if necessary.

Neutropenic patients and organ transplant recipients are at increased risk for developing Aspergillus infections. Testing Blood cultures are rarely positive. The initial test for suspected invasive aspergillosis is either serum galactomannan assay or, if negative, bronchoalveolar lavage with PCR test- ing followed by tissue biopsy if necessary. Treatment Voriconazole is first-line treatment in patients with documented or suspected invasive aspergillosis. Surgical resection is indicated for aspergilloma and hemoptysis and is con sidered definitive therapy. Treat allergic bronchopulmonary aspergillosis with inhaled or oral glucocorticoids. DOil'T BE TRICKED . Patients with aspergilloma who are asymptomatic and have stable x-rays do not require therapy. Aspergilloma: This enlarged image Irom a frontal chest x-ray shows a cavitary lesion (anowheads) contain- ing a round mass (anow) representing a fungus ball. 237

lnfectious Disease Diagnosis Consider catheter related infection in any patient with bacteremia or fever and a central venous catheter. Purulence and cel- lulitis around the catheter site are specific, but not sensitive, for catheter-related infection. Obtain two sets of peripheral blood cultures from different sites before starting empiric antibiotic therapy. Treatment Remove the catheter, then: . begin empiric antibiotics . confirm clearance of bacteremia with follow-up blood cultures . evaluate with echocardiography o evaluate patients with candidemia for Condido endophthalmitis STUDY TABLE: Management of CentralVenous Catheter-Related Bloodstream lnfection Based on Pathogen" Organism Treatment Uncomplicatedb Coagulase-negative staphylococci Remove catheter; antimicrobialtherapy for 5-7 days lf catheter is not removed, systemic antimicrobials and antimicrobial lock treatment'for 1 0-1 4 days Staphylococcus aureus (no active Remove catheter; antimicrobials for >14 days (usually 4 weeks) malignancy or immunosuppression) Enterococcus species Remove catheter; antimicrobials for 7-14 days Gram-negative bacilli Remove catheter; antimicrobials f or 7 -14 days Candida s (no retinitis) Remove catheter; antifungal agent for 14 additional after first blood culture Complicated Suppurative thrombophlebitis, Remove catheter; antimicrobials for 4-6 weeks (6-8 weeks for osteomyelitis) endocarditis, osteomyelitis, other site of metastatic or deep-seated infection : "Sho(-termcatheters. bBloodstream lnfection and fever resolve in 72 hours; no intravascular hardware, no endocarditis or suppurative thrombophlebitis. 'Antimicrobial solutlon (such as vancomycin) instilled into the lumen of a catheter and removed after a specified period. Staphyl ococcal Bacterem ia Endocarditis and vertebral diskitis and osteomyelitis are the two significant complications of S. aureus bacteremia.

Staphylococcus aureus (no active Remove catheter; antimicrobials for >14 days (usually 4 weeks) malignancy or immunosuppression) Enterococcus species Remove catheter; antimicrobials for 7-14 days Gram-negative bacilli Remove catheter; antimicrobials f or 7 -14 days Candida s (no retinitis) Remove catheter; antifungal agent for 14 additional after first blood culture Complicated Suppurative thrombophlebitis, Remove catheter; antimicrobials for 4-6 weeks (6-8 weeks for osteomyelitis) endocarditis, osteomyelitis, other site of metastatic or deep-seated infection : "Sho(-termcatheters. bBloodstream lnfection and fever resolve in 72 hours; no intravascular hardware, no endocarditis or suppurative thrombophlebitis. 'Antimicrobial solutlon (such as vancomycin) instilled into the lumen of a catheter and removed after a specified period. Staphyl ococcal Bacterem ia Endocarditis and vertebral diskitis and osteomyelitis are the two significant complications of S. aureus bacteremia. Diagnosis Evaluate all patients with echocardiography. Blood cultures should be repeated every 2 to 4 days until results are negative. The median time to clearance of MRSA bacteremia is 7 to 9 days. Treatment Bacteremia caused by MSSA is treated with IV penicillinase-resistant semisynthetic penicillin (such as oxacillin) or first generation cephalosporin (such as cefazolin). Bacteremia caused by MRSA is treated with vancomycin or daptomycin. Vancomycin should not be used when the isolate has a minimum inhibitory concentration >2 pg/ml; daptomycin is an acceptable alternative if the isolate is susceptible. 250 : t

Infectious Disease Uncomplicated infection should be treated with IV antibiotics for 2 weeks. Bacteremia beyond 72 hours requires additional evaluation and a longer course of antibiotics (4-6 weeks). DON'T BE TRICKED o Do not use vancomycin, because it is associated with higher rates of relapse and microbiologic failure in the treatment of MSSA bacteremia. o Patients with concomitant S. oureus pneumonia should not receive daptomycin, because it is inactivated by surfactant. Hospital-Acquired and Ventilator-Associated Pneumonia Prevention HAP is defined as pneumonia that occurs >48 hours after admission. VAB a subset of HAB is defined as occurring >48 hours after endotracheal intubation. Procedures to reduce VAP include: . minimizing sedation . following daily weaning protocols for timely extubation . keeping the head ofthe bed elevated >30 degrees o avoiding nasal intubation and nasogastric tubes . using chlorhexidine mouth rinse and subglottic suction catheters o facilitating early mobility Diagnosis The diagnosis of HAP is based on a new or progressive radiographic infiltrate plus clinical signs of pneumonia (fever, purulent sputum, leukocytosis, hypoxemia). Obtain specimen for culture. Treatment The main risk factor for MRSA, antibiotic-resistant Pseudomonqs, or other antibiotic-resistant pathogens is intravenous antibiotic use within the past 90 days. Additional risk factors for antibiotic-resistant pathogens associated with VAP are: . septic shock at the time of VAP o ARDS precedingVAP o 5 or more days of hospitalization before VAP o kidney replacement therapy before VAP Initiate empiric antibiotic therapy for HAP or VAP pending culture results. . Cover S. oureus with vancomycin or linezolid if MRSA resistance risk factors are present or MRSA prevalence is >107, or unknown. 251

lnfectious Disease . Cover Pseudomonaswith two antipseudomonal agents of dilferent classes (e'g., piperacillin tazobactam plus gentamicin) if resistance risk factors are present, prevalence is >10%, or bronchiectasis or cystic fibrosis is present. Choose monotherapy with cefepime, piperacillin-tazobactam, or levofloxacin for patients with no resistance risk factors; choose one agent to treat MSSA (e.g., naf'cillin) in patients with no risk factors for MRSA. Narrow the empiric therapy based on culture results. DON'T BE TRICKED . Do not delay empiric antibiotic therapy to perform diagnostic studies. TEST YOURSELF A 7S-year-old woman was admitted from home for treatment of a hip fracture. Four days after admission, she develops a tempera ture of 38.3'C (100.9'F) and a cough. A chest x ray shows a new left lower lobe infiltrate. ANSWER: For diagnosis, choose HAP; for treatment, select cefepime, piperacillin-tazobactam, or levofloxacin and nafcillin. Cl o stri d i oi d e s d iffi ci I e Diagnosis Diagnosis is commonly made by combining EIA tests for glutamine dehydrogenase plus toxin. Positive concordant tests rule in and negative concordant tests rule out C. dfficile infection. Discordant test results require NAAT testing for toxin genes. Alternatively, positive concordant NAAT for toxin genes and toxin EIA tests are diagnostic. Management ot' C. difJicile infection is based on disease severity. Severe disease is defined by any one of the following: o leukocyte count >15,000/pL . serum creatinine level >1.5 mg/dl Hospitalized patients with known or suspected illness should be placed under contact isolation. Treatment Discontinue the offending antibiotic. First line treatment for an initial mild or severe C. difficile infection is oral vancomycin or fidaxomicin. Fulminant disease is defined by the presence of shock, hypotension, toxic megacolon, or ileus. Treatment includes oral vancomycin, lV metronida zole, and possibly vancomycin enemas. A first recurrence is treated with a vancomycin pulse/slow taper regimen or with tidax- omicin. Fecal microbiota transplant is used for patients with multiple relapses. DOT{'T BE TRICKED r Do not obtain stool cultures to diagnose C. dfficileinfection. HIV lnfection Prevention Preexposure prophylaxis may be initiated in adults at high risk with daily combination emtricitabine and either tenofovir disoproxil fumarate or tenofovir alafenamide. 252

Infectious Disease Postexposure prophylaxis should be started within 72 hours following HIV exposure with tenofovir, emtricitabine, and raltegravir or dolutegravir for 4 weeks. Testing for HIV should be done immediately and at 4 to 6 weeks, 12 weeks, and 4 to 6 months. Screening Select universal HIV screening in all adults at least once and at least annually for those at high risk. Screen using the following protocol: . Start with a fourth-generation combination immunoassay that includes an EIA for HIV antibody (HIV-I and HIV-2) and HIV p24 antigen. o If combination immunoassay is positive, obtain immunoassay to differentiate HIV-I from HIV-2. . HIV-1 or HIV-2 antibody detection confirms the diagnosis. o If differentiation immunoassay is inconclusive for either HIV 1 or HIV-2, obtain NAAT, o A positive NAAT in the setting of a negative antibody test indicates acute HIV infection. DON'T BE TRICKED r If a test is positive on the initial antigen/antibody combination immunoassay but negative on the antibody differentiation immunoassay and NAAT testing, the initial test result was a false positive. Diagnosis Diagnose primary HIV infection (initial acute HIV infection) by a febrile illness that occurs within several weeks of a potential HIV exposure. Additional symptoms may include fatigue, lymphadenopathy, pharyngitis, rash, and/or headache. Certain diagnoses warrant HIV testing: . severe or treatment refractory HSV infection r oral thrush or esophageal candidiasis . PneumocAstis jirouecii pneumonitis . cryptococcal meningitis r disseminated mycobacterial infection . CMV retinitis or GI disease o toxoplasmosis . severe seborrheic dermatitis, or new or severe psoriasis o recurrent herpes zoster infections Testing AII positive rapid HIV tests must be confirmed with a fourth generation combination immunoassay. Treatment Consider initiating treatment in any patients motivated to start lifelong medication, regardless of CD4 cell count' Perform resistance testing at baseline.

. severe or treatment refractory HSV infection r oral thrush or esophageal candidiasis . PneumocAstis jirouecii pneumonitis . cryptococcal meningitis r disseminated mycobacterial infection . CMV retinitis or GI disease o toxoplasmosis . severe seborrheic dermatitis, or new or severe psoriasis o recurrent herpes zoster infections Testing AII positive rapid HIV tests must be confirmed with a fourth generation combination immunoassay. Treatment Consider initiating treatment in any patients motivated to start lifelong medication, regardless of CD4 cell count' Perform resistance testing at baseline. Select three drugs from two different classes, preferably combining two nucleoside reverse transcriptase inhibitors with an integrase strand transfer inhibitor. Select patients may be treated with dolutegravir plus lamivudine, but not as an initial regi men in those with a pretreatment HIV RNA level >500,000 copies/ml; do not use in those with chronic HBV infection or in those who will initiate treatment before the results of genotype testing and hepatitis B testing are known' 253

lnfectious Disease Viral load should fall quickly and progressively and reach undetectable levels within a few months. Pregnant women should promptly initiate or continue receiving HIV treatment without interruption. IRIS is an intense inflammatory disorder associated with paradoxical worsening of preexisting inlectious processes following the initiation of ART. The most important therapy lor IRIS is treatment of the underlying infection. Glucocorticoids and NSAIDS are sometimes added to decrease the inflammatory response. TESTYOURSELF A29 year old man with recently diagnosed pulmonary TB is found to have late-stage HIV infection. Three-drug ART and four drug TB therapy are initiated, and he quickly improves. Four weeks later. he develops recurrent fever and neck pain and swelling. He has bilateral tender cervical lymphadenopathy. ANSWER: For diagnosis, choose IRIS. For treatment, choose to continue ART and administer antituberculous drugs. DON'T BE TRICKED . Do not stop ART in the setting of IRIS STUDY TABLE: Prophylaxis for Patients With HIV lnfection Preventable Condition When Agent P. ji rove cii pneumonitis CD4 cell count <200/pL Tri methopri m-su lfa methoxazole Toxoplasmosis CD4 cell count <100/trrL and Trimethopri m-sulfamethoxazole positive lgG for toxoplasmosis MAC infection CD4 cell count <50/pL Azithromycin or clarithromycin Latent TB TST>5 mm or positive IGRA 3 months of isoniazid plus rifapentine given once weekly

Toxoplasmosis CD4 cell count <100/trrL and Trimethopri m-sulfamethoxazole positive lgG for toxoplasmosis MAC infection CD4 cell count <50/pL Azithromycin or clarithromycin Latent TB TST>5 mm or positive IGRA 3 months of isoniazid plus rifapentine given once weekly 3 months of isoniazid plus rifampin given daily lnfluenza Annual vaccination {or all lnactivated influenza vaccine HIV-infected patients Pneumococcal pneumonia Upon diagnosis Pneumococcal conjugate vaccine (PCV1 3) and pneumococcal polysaccharide vaccine (PPSV23) See General lnternal Medicine, Screening and Prevention Hepatiti B Completion of vaccine series if Hepatitis B vaccine not already immune or infected Meningococcal meningitis At diagnosis, then every 5 years Ouad rivalent meningococcal vaccine Discontinue P. jirouecii, toxoplasmosis, and MAC prophylaxis when ART produces CD4 cell counts >200/pL and the viral load is undetectable for at least 3 months. Influenza, Tdap, hepatitis A, and HpV vaccinations are indicated as for the general population. DON'T BE TRICKED o Live vaccines are contraindicated in immunocompromised patients, but the MMR, varicella, and recombinant zoster vaccines can be given to patients with HIV with CD4 cell counts >200/pL. Pneu mocystis ji rovecii Pneu mon ia Diagnosis In patients inf'ected with HIV, symptoms of p jirouecii pneumonia are gradual in onset and characterized by nonproductive cough and progressive dyspnea. Typical chest x ray findings include diffuse bilateral, interstitial l infiltrates. ? 254