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Viral lnfections airborne route; it is also the only HHV with a vaccine that KEY POI llTS (continued) produces protective humoral immunity. Antivirals are avail- o Intravenous acyclovir is used for severe mucocutaneous able for some HHVs, and immunoglobulin therapy is avail- herpes, disseminated infections in immunosuppressed able for cytomegalovirus and VZV. persons, esophagitis, and suspected HSV encephalitis.

airborne route; it is also the only HHV with a vaccine that KEY POI llTS (continued) produces protective humoral immunity. Antivirals are avail- o Intravenous acyclovir is used for severe mucocutaneous able for some HHVs, and immunoglobulin therapy is avail- herpes, disseminated infections in immunosuppressed able for cytomegalovirus and VZV. persons, esophagitis, and suspected HSV encephalitis. Herpes Simplex Virus Types 1 and 2 Herpes simplex virus (HSV) Upe 1 infection is transmitted by Va ricel la-Zoster Virus oral-oral or oral-genital contact. It typically causes painful, Overview small vesicles on an erythematous base, transitioning to pus- VZV (HHV-3) is transmitted by inhalation and colonization of tules and subsequent crusting of the lesions; erosions or the respiratory tract, with subsequent viremic dissemination ulcers may also develop. It affects 48% of adults. During to skin, liver, spleen, and sensory ganglia (varicella). VZV stress, severe illness, or immunosuppression, patients may establishes latency in the ganglia and can later reactivate, experience recurrence of oral stomatitis or esophagitis. The causing herpes zoster (shingles), especially in adults older incidence of primary genital infection by HSV 1is increasing than 60 years or in immunosuppressed patients. Contact and (see Sexually Transmitted Infections). HSV-1 is the most airborne precautions should be used for all hospitalized common cause of viral encephalitis (see Central Nervous patients with varicella, for patients with disseminated herpes System Infections). zoster, and for those with dermatomal zoster who are HSV-2 is sexually transmitted and typically causes geni- immunosuppressed. tal and rectal ulcers with or without proctitis. HSV-2 affects approximately one sixth of adults in the United States; it can Clinical Features and Diagnosis cause recurrent benign lymphocytic meningitis (Mollaret Primary varicella infection (chickenpox, Figure 4o) pre meningitis), myelitis, sacral radiculopathy, and neonatal sents with a febrile pruritic vesicular rash affecting the skin infection or death (maternofetal transmission in primary and mucocutaneous surfaces (oropharynx, conjunctiva, genital infection). Patients should be counseled regarding genitals); the rash commonly begins on the face and trunk, the natural history of infection and informed that asympto- then spreads to the extremities (centripetal distribution). matic viral shedding is the most common source of HSV Lesions present in various stages of development on any one transmission to sexual partners. Condoms and abstinence part of the body and include macules, papules, vesicles, and from sexual activity when lesions are present and suppres- scabs. Skin lesions may become superinfected with sive therapy to reduce the risk of transmission should be Streptococcus pAogenes or Staphylococcus aureus (impe- discussed. Men and women should be counseled about the tigo). Most children recover without sequelae, but adults risks of neonatal HSV infection. Women should be advised to may develop pneumonia, encephalitis, hepatitis, and cere- inform their obstetric provider and pediatrician of HSV bellar ataxia. infection in themselves or their sexual partner if they Herpes zoster typically causes a painful vesicular rash become pregnant. HSV-I and HSV-2 can cause herpetic that follows a dermatomal distribution that does not cross whitlow (on fingers), herpes gladiatorum (a skin infection the midline (see MKSAP 19 General Internal Medicine 2). typically associated with contact sports), keratoconjunctivi- Young patients presenting with herpes zoster should be tis, and retinitis and can trigger the occurrence of erythema multiforme. Initial infection with HSV-1 or HSV-2 is usually associ ated with more severe illness than episodes of reactivation. HSV-1 and HSV-2 infections can be treated and suppressed with oral nucleoside analogues (acyclovir, valacyclovir, and famciclovir). Topical antiviral agents (trifluridine and vidara- bine) are used for herpetic keratitis. Intravenous acyclovir is used for severe mucocutaneous disease, disseminated infec- tions in immunosuppressed persons, esophagitis, and sus- pected HSV encephalitis.

Herpes Simplex Virus Types 1 and 2 Herpes simplex virus (HSV) Upe 1 infection is transmitted by Va ricel la-Zoster Virus oral-oral or oral-genital contact. It typically causes painful, Overview small vesicles on an erythematous base, transitioning to pus- VZV (HHV-3) is transmitted by inhalation and colonization of tules and subsequent crusting of the lesions; erosions or the respiratory tract, with subsequent viremic dissemination ulcers may also develop. It affects 48% of adults. During to skin, liver, spleen, and sensory ganglia (varicella). VZV stress, severe illness, or immunosuppression, patients may establishes latency in the ganglia and can later reactivate, experience recurrence of oral stomatitis or esophagitis. The causing herpes zoster (shingles), especially in adults older incidence of primary genital infection by HSV 1is increasing than 60 years or in immunosuppressed patients. Contact and (see Sexually Transmitted Infections). HSV-1 is the most airborne precautions should be used for all hospitalized common cause of viral encephalitis (see Central Nervous patients with varicella, for patients with disseminated herpes System Infections). zoster, and for those with dermatomal zoster who are HSV-2 is sexually transmitted and typically causes geni- immunosuppressed. tal and rectal ulcers with or without proctitis. HSV-2 affects approximately one sixth of adults in the United States; it can Clinical Features and Diagnosis cause recurrent benign lymphocytic meningitis (Mollaret Primary varicella infection (chickenpox, Figure 4o) pre meningitis), myelitis, sacral radiculopathy, and neonatal sents with a febrile pruritic vesicular rash affecting the skin infection or death (maternofetal transmission in primary and mucocutaneous surfaces (oropharynx, conjunctiva, genital infection). Patients should be counseled regarding genitals); the rash commonly begins on the face and trunk, the natural history of infection and informed that asympto- then spreads to the extremities (centripetal distribution). matic viral shedding is the most common source of HSV Lesions present in various stages of development on any one transmission to sexual partners. Condoms and abstinence part of the body and include macules, papules, vesicles, and from sexual activity when lesions are present and suppres- scabs. Skin lesions may become superinfected with sive therapy to reduce the risk of transmission should be Streptococcus pAogenes or Staphylococcus aureus (impe- discussed. Men and women should be counseled about the tigo). Most children recover without sequelae, but adults risks of neonatal HSV infection. Women should be advised to may develop pneumonia, encephalitis, hepatitis, and cere- inform their obstetric provider and pediatrician of HSV bellar ataxia. infection in themselves or their sexual partner if they Herpes zoster typically causes a painful vesicular rash become pregnant. HSV-I and HSV-2 can cause herpetic that follows a dermatomal distribution that does not cross whitlow (on fingers), herpes gladiatorum (a skin infection the midline (see MKSAP 19 General Internal Medicine 2). typically associated with contact sports), keratoconjunctivi- Young patients presenting with herpes zoster should be tis, and retinitis and can trigger the occurrence of erythema multiforme. Initial infection with HSV-1 or HSV-2 is usually associ ated with more severe illness than episodes of reactivation. HSV-1 and HSV-2 infections can be treated and suppressed with oral nucleoside analogues (acyclovir, valacyclovir, and famciclovir). Topical antiviral agents (trifluridine and vidara- bine) are used for herpetic keratitis. Intravenous acyclovir is used for severe mucocutaneous disease, disseminated infec- tions in immunosuppressed persons, esophagitis, and sus- pected HSV encephalitis. KEY POIl{TS o The incidence of primary genital infection caused by herpes simplex virus (HSV) type 1is increasing, and patients should be informed that asymptomatic viral shedding is the most common source of HSV transmis- t I G U R E 4 0. Varicella (chickenpox) represents the primary infection with varicella-zoster virus and is a highly contagious disease characterized by a sion to sexual partners' (continued) generalized vesicular rash that spreads from the scalp and face to the trunk and extrem ities.

KEY POIl{TS o The incidence of primary genital infection caused by herpes simplex virus (HSV) type 1is increasing, and patients should be informed that asymptomatic viral shedding is the most common source of HSV transmis- t I G U R E 4 0. Varicella (chickenpox) represents the primary infection with varicella-zoster virus and is a highly contagious disease characterized by a sion to sexual partners' (continued) generalized vesicular rash that spreads from the scalp and face to the trunk and extrem ities. 100

Viral lnfections tested for HIV. Immunosuppressed patients, including preg t(EY POrr{T5 nant women, can present with multiple dermatomes affected o The rash of primary varicella infection (chickenpox) or with disseminated disease. Postherpetic neuralgia, defined commonly begins on the face and trunk, then spreads as neuropathic pain lasting more than 1 month after resolu- to the extremities and presents in various stages of tion of the vesicular rash, is the most significant complica- development on any one part of the body (macules, tion of herpes zoster. Other complications include herpes papules, vesicles, and scabs). zoster ophthalmicus with visual loss, Ramsay Hunt syn- drome (Figure 41), pneumonia, hepatitis, and central nerv- o In immunosuppressed patients, herpes zoster (shingles) ous system complications (see Central Nervous System can affect multiple dermatomes or present with dissem- Infections). inated disease; young patients presenting with herpes Varicella or herpes zoster can be diagnosed clinically by zoster should be tested for HIV the typical vesicular rash and confirmed with VZV PCR testing o Postexposure varicella vaccination is appropriate in of the base of a vesicular lesion. immunocompetent persons, and varicella-zoster immune globulin should be used in immunocompro- Management mised adults and pregnant women. Antiviral therapy (acyclovir, valacyclovir, and famciclovir) o Antiviral therapy speeds recovery and decreases the speeds recovery and decreases the severity and duration of severity and duration of neuropathic pain if begun neuropathic pain if begun within 72 hours of VZV rash within 72 hours of varicella-zoster rash onset. onset. Intravenous acyclovir should be used for immunosup- pressed or hospitalized patients and those with neurologic Epstein-Barr Virus involvement. Epstein-Barr virus (fgV) (HHV-4) is highly prevalent; sero Immunization of patients older than 50 years with the logic studies show evidence of previous EBV infection in recombinant subunit vaccine is the most important pre- almost all adults. It is most commonly transmitted by saliva ventive strategy (see MKSAP 19 General Internal Medicine and is the main cause of infectious mononucleosis in chil 2). Postexposure prophylaxis should be provided to sus- dren and adolescents. Patients present with fever, severe ceptible persons (VZV IgG negative); postexposure vari- fatigue, exudative pharyngitis, cervical and axillary lym- cella vaccination is appropriate in immunocompetent phadenopathy, and splenomegaly. Atypical lymphocytosis persons, and variceila-zoster immune globulin should be and aminotransferase level elevations are clues to the diagno- used in immunocompromised adults and in pregnant sis, which is established by the presence of heterophile anti- women. bodies (Monospot test) or IgM to the EBV viral capsid antigen. The Monospot test result may be negative in the first week of illness. Treatment is supportive; glucocorticoids may be given to patients with autoimmune hemolytic anemia, cen- tral nervous system involvement, or tonsillar enlargement with a compromised airway. EBV is associated with the development of T-cell and B-cell lymphomas, Hodgkin and Burkitt lymphoma, nasopharyngeal carcinoma, and post- transplant lymphoproliferative disease in solid organ transplantation. rEY POIilT5 . Epstein-Barr virus infection, the primary cause of infec- tious mononucleosis, presents with fever, severe fatigue, exudative pharyngitis, cervical and axillary lymphade- nopathy, and splenomegaly. o The presence of heterophile antibodies on the Monospot test establishes the diagnosis of Epstein-Barr virus, although the test result may be negative during the first week of illness.

tested for HIV. Immunosuppressed patients, including preg t(EY POrr{T5 nant women, can present with multiple dermatomes affected o The rash of primary varicella infection (chickenpox) or with disseminated disease. Postherpetic neuralgia, defined commonly begins on the face and trunk, then spreads as neuropathic pain lasting more than 1 month after resolu- to the extremities and presents in various stages of tion of the vesicular rash, is the most significant complica- development on any one part of the body (macules, tion of herpes zoster. Other complications include herpes papules, vesicles, and scabs). zoster ophthalmicus with visual loss, Ramsay Hunt syn- drome (Figure 41), pneumonia, hepatitis, and central nerv- o In immunosuppressed patients, herpes zoster (shingles) ous system complications (see Central Nervous System can affect multiple dermatomes or present with dissem- Infections). inated disease; young patients presenting with herpes Varicella or herpes zoster can be diagnosed clinically by zoster should be tested for HIV the typical vesicular rash and confirmed with VZV PCR testing o Postexposure varicella vaccination is appropriate in of the base of a vesicular lesion. immunocompetent persons, and varicella-zoster immune globulin should be used in immunocompro- Management mised adults and pregnant women. Antiviral therapy (acyclovir, valacyclovir, and famciclovir) o Antiviral therapy speeds recovery and decreases the speeds recovery and decreases the severity and duration of severity and duration of neuropathic pain if begun neuropathic pain if begun within 72 hours of VZV rash within 72 hours of varicella-zoster rash onset. onset. Intravenous acyclovir should be used for immunosup- pressed or hospitalized patients and those with neurologic Epstein-Barr Virus involvement. Epstein-Barr virus (fgV) (HHV-4) is highly prevalent; sero Immunization of patients older than 50 years with the logic studies show evidence of previous EBV infection in recombinant subunit vaccine is the most important pre- almost all adults. It is most commonly transmitted by saliva ventive strategy (see MKSAP 19 General Internal Medicine and is the main cause of infectious mononucleosis in chil 2). Postexposure prophylaxis should be provided to sus- dren and adolescents. Patients present with fever, severe ceptible persons (VZV IgG negative); postexposure vari- fatigue, exudative pharyngitis, cervical and axillary lym- cella vaccination is appropriate in immunocompetent phadenopathy, and splenomegaly. Atypical lymphocytosis persons, and variceila-zoster immune globulin should be and aminotransferase level elevations are clues to the diagno- used in immunocompromised adults and in pregnant sis, which is established by the presence of heterophile anti- women. bodies (Monospot test) or IgM to the EBV viral capsid antigen. The Monospot test result may be negative in the first week of illness. Treatment is supportive; glucocorticoids may be given to patients with autoimmune hemolytic anemia, cen- tral nervous system involvement, or tonsillar enlargement with a compromised airway. EBV is associated with the development of T-cell and B-cell lymphomas, Hodgkin and Burkitt lymphoma, nasopharyngeal carcinoma, and post- transplant lymphoproliferative disease in solid organ transplantation. rEY POIilT5 . Epstein-Barr virus infection, the primary cause of infec- tious mononucleosis, presents with fever, severe fatigue, exudative pharyngitis, cervical and axillary lymphade- nopathy, and splenomegaly. o The presence of heterophile antibodies on the Monospot test establishes the diagnosis of Epstein-Barr virus, although the test result may be negative during the first week of illness. Human Cytomegalovirus Cytomegalovirus (HHV-S) infections are most commonly t t G U R E 41 . These vesicular lesions on and in the ear canal, along with ipsilateral peripheralfacial palsy and altered taste, are characteristic of Ramsay asymptomatic but may present with a mononucleosis-like Hunt syndrome caused by varicella-zoster virus infection. syndrome without pharyngitis and with negative heterophile

Human Cytomegalovirus Cytomegalovirus (HHV-S) infections are most commonly t t G U R E 41 . These vesicular lesions on and in the ear canal, along with ipsilateral peripheralfacial palsy and altered taste, are characteristic of Ramsay asymptomatic but may present with a mononucleosis-like Hunt syndrome caused by varicella-zoster virus infection. syndrome without pharyngitis and with negative heterophile 101

Viral lnfections . Serologrc assays for cytomegalovirus have limited diag- nostic utility because most adults are seropositive; how- ever, they are performed routinely in pretransplant evaluations to assess the risk of cytomegalovirus reacti- vation following transplantation and to determine appropriate prophylaxis. o Diagnosis of cytomegalovirus is confirmed with molecu- lar tests of infected fluids, by demonstrating typical cytopathic "owl's-eye" intracellular inclusions on biopsy specimens, or by cytomegalovirus immunostaining of pathologic samples.

. Serologrc assays for cytomegalovirus have limited diag- nostic utility because most adults are seropositive; how- ever, they are performed routinely in pretransplant evaluations to assess the risk of cytomegalovirus reacti- vation following transplantation and to determine appropriate prophylaxis. o Diagnosis of cytomegalovirus is confirmed with molecu- lar tests of infected fluids, by demonstrating typical cytopathic "owl's-eye" intracellular inclusions on biopsy specimens, or by cytomegalovirus immunostaining of pathologic samples. Re-Emerg i ng Vacci ne-Preventa ble FIGURE 4 2. Under a magnification of 500X, a photomicrograph of a sample of Viral Infections kidney tissue reveals the presence of what are referred t0 as cytomegalic inclusion Measles has re-emerged in the United States after being cells. With enlarged, darkly stained nuclei, such cells are also known as owl's-eye eliminated in 2000. This resurgence is owing to low vaccina- inclusion cells and are caused by cytomegalic inclusion disease resulting from cytomegalovirus. tion rates in the population and reintroduction of the virus from endemic countries. Mandatory vaccination has been implemented in New York City to curb the outbreaks. antibody results. Qrtomegalovirus may be transmitted through Measles is a highly contagious viral infection that presents saliva, blood transfusion, organ transplantation (cytomegalovi- with high fever, rhinorrhea, cough, Koplik spots (Figure 43), rus-positive donor to cytomegalovirus-seronegative recipient), conjunctivitis, and a diffuse macular rash. Complications the placenta (congenital cytomegalovirus), or by breastfeeding. Approximately 60% to 9O"/. of adults have latent cytomegalovi- rus infectionwith disease reactivation more common in immu- nosuppressed persons (those with AIDS, transplant recipients, those receiving glucocorticoid therapy). Cltomegalovirus can cause retinitis, pneumonitis, hepatitis, bone marrow suppres- sion, colitis, esophagitis, and adrenalitis in immunocompro- mised persons. Immunocompetent patients occasionally also present with colitis. Because cytomegalovirus can cause numerous clinical manifestations, a high index of clinical suspicion is impor- tant. Diagnosis is commonly confirmed with molecular tests, such as PCR testing of serum, bronchoalveolar lavage fluid, or cerebrospinal fluid, or by demonstrating typical cytopathic "owl's-eye" intracellular inclusions on biopsy specimens (Figure 42). Pathologic diagnosis is confirmed by cytomeg- alovirus immunostains. Serologic assays have limited diag- nostic utility because most adults are seropositive; however, they are performed routinely in pretransplant evaluations to assess the risk of cytomegalovirus reactivation after trans- plantation and to determine appropriate prophylaxis. Antiviral therapy with intravenous ganciclovir or oral valganciclovir is used in immunocompromised patients or in immunocompetent patients with severe disease. Oral valgan- ciclovir is also used as prophylaxis or pre-emptive therapy (treat if the PCR serum testing converts to positive) in trans- plant recipients. Foscarnet and cidofovir can be used in instances of ganciclovir resistance or intolerance. Letermovir FIGURE 43. Koplikspots are small,l to 3-mm whitish papules on an erythematous base, first appearing on the buccal mucosa opposite the molar teeth is the most recent FDA-approved drug to prevent cytomeg- before spreading to cover the buccal and labial mucosa and the hard and soft alovirus infection in bone marrow transplant recipients. palate. Koplik spots are very specific for measles.

Re-Emerg i ng Vacci ne-Preventa ble FIGURE 4 2. Under a magnification of 500X, a photomicrograph of a sample of Viral Infections kidney tissue reveals the presence of what are referred t0 as cytomegalic inclusion Measles has re-emerged in the United States after being cells. With enlarged, darkly stained nuclei, such cells are also known as owl's-eye eliminated in 2000. This resurgence is owing to low vaccina- inclusion cells and are caused by cytomegalic inclusion disease resulting from cytomegalovirus. tion rates in the population and reintroduction of the virus from endemic countries. Mandatory vaccination has been implemented in New York City to curb the outbreaks. antibody results. Qrtomegalovirus may be transmitted through Measles is a highly contagious viral infection that presents saliva, blood transfusion, organ transplantation (cytomegalovi- with high fever, rhinorrhea, cough, Koplik spots (Figure 43), rus-positive donor to cytomegalovirus-seronegative recipient), conjunctivitis, and a diffuse macular rash. Complications the placenta (congenital cytomegalovirus), or by breastfeeding. Approximately 60% to 9O"/. of adults have latent cytomegalovi- rus infectionwith disease reactivation more common in immu- nosuppressed persons (those with AIDS, transplant recipients, those receiving glucocorticoid therapy). Cltomegalovirus can cause retinitis, pneumonitis, hepatitis, bone marrow suppres- sion, colitis, esophagitis, and adrenalitis in immunocompro- mised persons. Immunocompetent patients occasionally also present with colitis. Because cytomegalovirus can cause numerous clinical manifestations, a high index of clinical suspicion is impor- tant. Diagnosis is commonly confirmed with molecular tests, such as PCR testing of serum, bronchoalveolar lavage fluid, or cerebrospinal fluid, or by demonstrating typical cytopathic "owl's-eye" intracellular inclusions on biopsy specimens (Figure 42). Pathologic diagnosis is confirmed by cytomeg- alovirus immunostains. Serologic assays have limited diag- nostic utility because most adults are seropositive; however, they are performed routinely in pretransplant evaluations to assess the risk of cytomegalovirus reactivation after trans- plantation and to determine appropriate prophylaxis. Antiviral therapy with intravenous ganciclovir or oral valganciclovir is used in immunocompromised patients or in immunocompetent patients with severe disease. Oral valgan- ciclovir is also used as prophylaxis or pre-emptive therapy (treat if the PCR serum testing converts to positive) in trans- plant recipients. Foscarnet and cidofovir can be used in instances of ganciclovir resistance or intolerance. Letermovir FIGURE 43. Koplikspots are small,l to 3-mm whitish papules on an erythematous base, first appearing on the buccal mucosa opposite the molar teeth is the most recent FDA-approved drug to prevent cytomeg- before spreading to cover the buccal and labial mucosa and the hard and soft alovirus infection in bone marrow transplant recipients. palate. Koplik spots are very specific for measles. 102

Stewardship and Emerging Resistance include otitis media, pneumonia, encephalitis, subacute selection, dosing, therapy duration, and route of adminis- sclerosing panencephalitis, and death. Adults, pregnant tration are also considered. Furthermore, antimicrobial women, and immunocompromised persons are at high risk stewardship teams, including an infectious disease physi- of more severe illness and complications. Real-time PCR cian and a dedicated pharmacist, address simplifying unnec- detection of viral RNA in respiratory and urine samples and essary combination therapy, avoiding redundant double measles-specific IgM in serum confirm the diagnosis. anaerobic coverage, streamlining de-escalation, targeting Suspected cases should be reported to the local health antibiotics with a high risk of C. difficile infection (such as department within 24 hours. clindamycin, fluoroquinolones, and broad-spectrum antibi- Mumps has also re-emerged because of low vaccination otics), pharmacokinetic monitoring and dose adjustment, rates. Mumps typically cause parotitis associated with low- converting intravenous to oral agents, and raising awareness grade fever, headache, and malaise. Complications include of potential adverse effects (for example, increased risk with orchitis, meningitis, pancreatitis, encephalitis, and hearing fluoroquinolones for QT interval prolongation, aortic aneu- loss. Real-time PCR of a buccal swab confirms the diagnosis; rysm and dissection, hypoglycemia, and tendinitis and mumps-specific IgM can also be used. tendon rupture). The measles-mumps-rubella (MMR) vaccine (see MKSAP Combination therapy does not prevent the emergence of 19 General Internal Medicine 2) is the best way to prevent resistance. However, it may be considered in specific circum- infection, but it cannot be given to immunosuppressed per- stances, such as empiric therapy regimens, to broaden the sons because it contains a live-attenuated virus. spectrum of activity or provide coverage for potential antimi- crobial-resistant organisms pending culture and susceptibility results. Antibiotic combination therapy may also provide syn- ergistic activity in limited situations, such as enterococcal Stewardship and Emerging endocarditis and bacteremia caused by CRE. Resistance Conversion from an intravenous to an oral antimicrobial agent should be considered for ease of administration and to lntroduction limit intravenous catheter use. Factors supporting readiness Emergence of antibiotic resistance is potentiated by all antibi- for conversion include a temperature of 38 "C (100.4 "F) or less, otic use. Careful antibiotic use is essential to preserving the an improving leukocyte count, clinical stability and improve armamentarium. Approxim ately 269 million outpatient anti- ment of signs and symptoms related to infection, a functioning biotic prescriptions were dispensed in the United States in gastrointestinal tract, no indication for intravenous therapy 2015, and at least 30%, of these were considered unnecessary. (endocarditis, Stoph ylococcus aureus bacteremia), and avail- Most prescriptions are for acute respiratory infections (usu- ability of a suitable oral alternative with good oral bioavailabil- ally caused by viruses) and asymptomatic bacteriuria not ity (fluoroquinolones, metronidazole, or doxycycline, among requiring antibiotic treatment. Inpatient antibiotic use others). accounts for 38.5% of all antibiotic use; half of hospitalized rEY POIl{T patients receive antibiotics, and half of these medications are . Avoiding unnecessary antibiotic use, simplifying HVC considered unnecessary or inappropriate. The CDC and the unnecessary combination therapy, avoiding double World Health Organization developed comprehensive plans anaerobic coverage, converting intravenous to oral outlining urgent actions to combat antibiotic resistance; these agents, streamlining de-escalation, and minimizing include addressing carbapenem-resistant Enterobacteriaceae therapy duration are important components of antimi- (CRE) and other highly resistant gram-negative bacteria, crobial stewardship programs. developing improved diagnostics, and accelerating research for new antibiotics. Anti biotics for Anti biotic- Resista nt Antim icrobia I Stewa rdshi p Organisms An infectious diseases consultation should be considered for and the Value of Infestious infections with antibiotic-resistant organisms because few effec Disease Consultation tive antibiotics are available to treat these infections. Enterococcus Antibiotic stewardship refers to coordinated interventions faecium, S. aureus, Klebsiella pneumoniqe, Acinetobocter spe- to improve antibiotic use and clinical outcomes by promot- cies, Pseudomonas aeruginosa, and Enterobacter species are ing optimal antibiotic regimens. Goals include minimizing particular$ problematic antibiotic-resistant organisms. This adverse events (S% risk per antibiotic per patient), risk of group includes extended-spectrum B-lactamase (ESBL)- Clostridioides difficile infection, and emergence of resist- producing gram-negative bacteria and carbapenemase ance. A key responsibility of stewardship programs is avoid- producing CRE (I( pneumonioe carbapenemases [KPC] and ing antibiotic administration when not indicated. Antibiotic New Delhi metallo-p-lactamase) that destroy carbapenems.

include otitis media, pneumonia, encephalitis, subacute selection, dosing, therapy duration, and route of adminis- sclerosing panencephalitis, and death. Adults, pregnant tration are also considered. Furthermore, antimicrobial women, and immunocompromised persons are at high risk stewardship teams, including an infectious disease physi- of more severe illness and complications. Real-time PCR cian and a dedicated pharmacist, address simplifying unnec- detection of viral RNA in respiratory and urine samples and essary combination therapy, avoiding redundant double measles-specific IgM in serum confirm the diagnosis. anaerobic coverage, streamlining de-escalation, targeting Suspected cases should be reported to the local health antibiotics with a high risk of C. difficile infection (such as department within 24 hours. clindamycin, fluoroquinolones, and broad-spectrum antibi- Mumps has also re-emerged because of low vaccination otics), pharmacokinetic monitoring and dose adjustment, rates. Mumps typically cause parotitis associated with low- converting intravenous to oral agents, and raising awareness grade fever, headache, and malaise. Complications include of potential adverse effects (for example, increased risk with orchitis, meningitis, pancreatitis, encephalitis, and hearing fluoroquinolones for QT interval prolongation, aortic aneu- loss. Real-time PCR of a buccal swab confirms the diagnosis; rysm and dissection, hypoglycemia, and tendinitis and mumps-specific IgM can also be used. tendon rupture). The measles-mumps-rubella (MMR) vaccine (see MKSAP Combination therapy does not prevent the emergence of 19 General Internal Medicine 2) is the best way to prevent resistance. However, it may be considered in specific circum- infection, but it cannot be given to immunosuppressed per- stances, such as empiric therapy regimens, to broaden the sons because it contains a live-attenuated virus. spectrum of activity or provide coverage for potential antimi- crobial-resistant organisms pending culture and susceptibility results. Antibiotic combination therapy may also provide syn- ergistic activity in limited situations, such as enterococcal Stewardship and Emerging endocarditis and bacteremia caused by CRE. Resistance Conversion from an intravenous to an oral antimicrobial agent should be considered for ease of administration and to lntroduction limit intravenous catheter use. Factors supporting readiness Emergence of antibiotic resistance is potentiated by all antibi- for conversion include a temperature of 38 "C (100.4 "F) or less, otic use. Careful antibiotic use is essential to preserving the an improving leukocyte count, clinical stability and improve armamentarium. Approxim ately 269 million outpatient anti- ment of signs and symptoms related to infection, a functioning biotic prescriptions were dispensed in the United States in gastrointestinal tract, no indication for intravenous therapy 2015, and at least 30%, of these were considered unnecessary. (endocarditis, Stoph ylococcus aureus bacteremia), and avail- Most prescriptions are for acute respiratory infections (usu- ability of a suitable oral alternative with good oral bioavailabil- ally caused by viruses) and asymptomatic bacteriuria not ity (fluoroquinolones, metronidazole, or doxycycline, among requiring antibiotic treatment. Inpatient antibiotic use others). accounts for 38.5% of all antibiotic use; half of hospitalized rEY POIl{T patients receive antibiotics, and half of these medications are . Avoiding unnecessary antibiotic use, simplifying HVC considered unnecessary or inappropriate. The CDC and the unnecessary combination therapy, avoiding double World Health Organization developed comprehensive plans anaerobic coverage, converting intravenous to oral outlining urgent actions to combat antibiotic resistance; these agents, streamlining de-escalation, and minimizing include addressing carbapenem-resistant Enterobacteriaceae therapy duration are important components of antimi- (CRE) and other highly resistant gram-negative bacteria, crobial stewardship programs. developing improved diagnostics, and accelerating research for new antibiotics. Anti biotics for Anti biotic- Resista nt Antim icrobia I Stewa rdshi p Organisms An infectious diseases consultation should be considered for and the Value of Infestious infections with antibiotic-resistant organisms because few effec Disease Consultation tive antibiotics are available to treat these infections. Enterococcus Antibiotic stewardship refers to coordinated interventions faecium, S. aureus, Klebsiella pneumoniqe, Acinetobocter spe- to improve antibiotic use and clinical outcomes by promot- cies, Pseudomonas aeruginosa, and Enterobacter species are ing optimal antibiotic regimens. Goals include minimizing particular$ problematic antibiotic-resistant organisms. This adverse events (S% risk per antibiotic per patient), risk of group includes extended-spectrum B-lactamase (ESBL)- Clostridioides difficile infection, and emergence of resist- producing gram-negative bacteria and carbapenemase ance. A key responsibility of stewardship programs is avoid- producing CRE (I( pneumonioe carbapenemases [KPC] and ing antibiotic administration when not indicated. Antibiotic New Delhi metallo-p-lactamase) that destroy carbapenems. 103