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lnfectious Gastrointestinal Syndromes Agent Clinical Findings Diagnosis" Antimicrobial Treatmentb Bacterial Agent Campylobacter Fever, chills, diarrhea (watery or Routine stoolculture or NAAI Azithromycin; fluoroqu inolone bloody), crampy abdominal pain; blood culture such as ciprofloxacin (alternative) postinfection Gu i lain-Ba116 I

Agent Clinical Findings Diagnosis" Antimicrobial Treatmentb Bacterial Agent Campylobacter Fever, chills, diarrhea (watery or Routine stoolculture or NAAI Azithromycin; fluoroqu inolone bloody), crampy abdominal pain; blood culture such as ciprofloxacin (alternative) postinfection Gu i lain-Ba116 I syndrome, lBS, intestinal perfo ration, g lome ru lone ph ritis, erythema nodosum, hemolytic anemia, or reactive arthritis Shigella Dysentery (fever, abdom ina I Routine stool culture or NAAI Fluoroquinolone such as cram ps, tenesm us, bloody/m ucus- blood cultures (with severe ciprofloxacin, or azithromycin or filled stools; possibly vomiting); disease) ceftriaxone postinfection HUS, reactive arthritis, erythema nodosu m, glomerulonephritis, or IBS Salmonella Fevec chills, diarrhea (watery or Routine stool culture or NAAI Mild: none bloody), cramps, myalgia; blood cultures (moderate to severe bacteremia in 10o/o-257" of disease); bone marrow and Underlying disease or severe patients; postinfection reactive duodenal fluid cultures may also illness: fluoroquinolone such as arthritis, erythema nodosum, or IBS be helpful when enteric fever ciprofloxaci n and/or parenteral suspected thi rd-generation cephalospori n such as ceftriaxone EHEC/STEC, most Bloody stools in >80% of patients; Stool culture with specialized None commonly fever often absent or low grade; media and immunoassay for Shiga Escherichia coli may be associated with HUS toxin or NAATfor gene(s)encoding 0157:H7 Shiga toxin ETEC (travelers' Non bloody, watery stools; None-usually a clinical diagnosis Fluoroquinolone (such as diarrhea) constitutional sym ptoms rare ciprofloxaci n), azith romycin, or rifaximin Yersinia Fever, diarrhea, right lower Stool culture with specialized Fluoroquinolone such as quadrant pain (may mimic media (or culture of other involved ciprofloxacin appendicitis); pharyngitis; sites); NAAT i ntesti na I perforation; postinfection Third-generation cepha losporin reactive arth ritis, hemolytic anem ia, such as ceftriaxone plus or erythema nodosum gentamicin for severe disease

syndrome, lBS, intestinal perfo ration, g lome ru lone ph ritis, erythema nodosum, hemolytic anemia, or reactive arthritis Shigella Dysentery (fever, abdom ina I Routine stool culture or NAAI Fluoroquinolone such as cram ps, tenesm us, bloody/m ucus- blood cultures (with severe ciprofloxacin, or azithromycin or filled stools; possibly vomiting); disease) ceftriaxone postinfection HUS, reactive arthritis, erythema nodosu m, glomerulonephritis, or IBS Salmonella Fevec chills, diarrhea (watery or Routine stool culture or NAAI Mild: none bloody), cramps, myalgia; blood cultures (moderate to severe bacteremia in 10o/o-257" of disease); bone marrow and Underlying disease or severe patients; postinfection reactive duodenal fluid cultures may also illness: fluoroquinolone such as arthritis, erythema nodosum, or IBS be helpful when enteric fever ciprofloxaci n and/or parenteral suspected thi rd-generation cephalospori n such as ceftriaxone EHEC/STEC, most Bloody stools in >80% of patients; Stool culture with specialized None commonly fever often absent or low grade; media and immunoassay for Shiga Escherichia coli may be associated with HUS toxin or NAATfor gene(s)encoding 0157:H7 Shiga toxin ETEC (travelers' Non bloody, watery stools; None-usually a clinical diagnosis Fluoroquinolone (such as diarrhea) constitutional sym ptoms rare ciprofloxaci n), azith romycin, or rifaximin Yersinia Fever, diarrhea, right lower Stool culture with specialized Fluoroquinolone such as quadrant pain (may mimic media (or culture of other involved ciprofloxacin appendicitis); pharyngitis; sites); NAAT i ntesti na I perforation; postinfection Third-generation cepha losporin reactive arth ritis, hemolytic anem ia, such as ceftriaxone plus or erythema nodosum gentamicin for severe disease Vibrio Bloody stools (>25"/" of patients), Stool culture with specialized Usually no treatment unless parahaemolyticus fever, vomiting (>50% of patients) media (blood culture with invasive suspected invasive disease); NAAT Doxycycline, fluoroquinolone (such as ciprofloxacin), or azithromycin if treating severe noninvasive gastrointestinal illness Doxycycline plus ceftriaxone for invasive infection Clostridioides Diarrhea (gross blood in stool Stool NAAT alone or stool ElAtoxin Nonsevere: oral vancomycin or difficile uncommon), fever, abdominal test as part of stepwise approach, oral fidaxomicin; if neither is pain/cra mping, colonic d istention including NAAT plus toxin, or GDH available, oral metronidazole (with possible sepsis, hypotension, plus toxin, or GDH plus toxin Severe: oral vancomycin or ileus, toxic megacolon in fulminant followed by NAAT when results are fidaxomicin disease), leu kocytosis, acute kid ney discordant injury Fulminant: oral vancomycin, lV metronidazole, and (possibly) vancomycin enema

Vibrio Bloody stools (>25"/" of patients), Stool culture with specialized Usually no treatment unless parahaemolyticus fever, vomiting (>50% of patients) media (blood culture with invasive suspected invasive disease); NAAT Doxycycline, fluoroquinolone (such as ciprofloxacin), or azithromycin if treating severe noninvasive gastrointestinal illness Doxycycline plus ceftriaxone for invasive infection Clostridioides Diarrhea (gross blood in stool Stool NAAT alone or stool ElAtoxin Nonsevere: oral vancomycin or difficile uncommon), fever, abdominal test as part of stepwise approach, oral fidaxomicin; if neither is pain/cra mping, colonic d istention including NAAT plus toxin, or GDH available, oral metronidazole (with possible sepsis, hypotension, plus toxin, or GDH plus toxin Severe: oral vancomycin or ileus, toxic megacolon in fulminant followed by NAAT when results are fidaxomicin disease), leu kocytosis, acute kid ney discordant injury Fulminant: oral vancomycin, lV metronidazole, and (possibly) vancomycin enema Viral Norovirus Watery, noninflammatory diarrhea NAAT, particularly for outbreak None and fever; vomiting in >50% of investigations patients; shon incubation period and high attack rate (Continued on the next page)

Viral Norovirus Watery, noninflammatory diarrhea NAAT, particularly for outbreak None and fever; vomiting in >50% of investigations patients; shon incubation period and high attack rate (Continued on the next page) 59

Infectious Gastrointestinal Syndromes Causative Agents, Clinical Presentation, and Management of lnfectious Dia rrhea (Continued) TABLE 46. Agent Clinical Findings Diagnosis" Antimicrobial Treatmentb Parasitic Giardia Watery, "greasy", floating, foul- EIA or NAAT preferred; stool Tinidazole, nitazoxanide, or smelling diarrhea, abdominal microscopy for ova and parasites metronidazole crampi ng, nausea, steatorrhea, flatulence, weight loss; fever uncommon; posti nfection lactose intolerance or IBS CnJptosporidium Watery diarrhea; abdominal Modified acid-fast stain; direct Nitazoxanide cramping; malaise; weight loss fluorescent antibody Effective antiretrovi ra I thera py i n immunoassay; EIA; NAAT patients with HIV infection

Parasitic Giardia Watery, "greasy", floating, foul- EIA or NAAT preferred; stool Tinidazole, nitazoxanide, or smelling diarrhea, abdominal microscopy for ova and parasites metronidazole crampi ng, nausea, steatorrhea, flatulence, weight loss; fever uncommon; posti nfection lactose intolerance or IBS CnJptosporidium Watery diarrhea; abdominal Modified acid-fast stain; direct Nitazoxanide cramping; malaise; weight loss fluorescent antibody Effective antiretrovi ra I thera py i n immunoassay; EIA; NAAT patients with HIV infection Amebiasis Most asymptomatic; dysentery, Stool microscopy for ova and Ti nidazole or metronidazole abdominal pain, fevel weight loss; parasites; stool antigen followed by paromomycin or intesti na I perforation i mmunoassay; NAAI serologic diloxanide antibodies Cyclospora Watery diarrhea, bloating, Modified acid-fast stain; Tri meth o pri m -su lfa m eth oxazo le flatulence, weight loss, nausea, fl uorescence m icroscopy; NAAT anorexia, crampy abdominal pain; sometimes fever

Amebiasis Most asymptomatic; dysentery, Stool microscopy for ova and Ti nidazole or metronidazole abdominal pain, fevel weight loss; parasites; stool antigen followed by paromomycin or intesti na I perforation i mmunoassay; NAAI serologic diloxanide antibodies Cyclospora Watery diarrhea, bloating, Modified acid-fast stain; Tri meth o pri m -su lfa m eth oxazo le flatulence, weight loss, nausea, fl uorescence m icroscopy; NAAT anorexia, crampy abdominal pain; sometimes fever EHEC = enterohemorrh agic E. coli; EIA - enzyme immunoassay; ETEC = enterotoxigenic E. coli; GDH = glutamate dehydrogenase; HUS = hemolytic uremic syndrome; IBS = irritable bowel syndrome; lV = intravenous; NAAT = nucleic acid amplification test; PCR = polymerase chain reaction; STEC = Shiga toxin-producin g E. coli. bEmpiric treatment, with the final choice of the antimicrobial agent to use guided by in vitro susceptibility testing.

EHEC = enterohemorrh agic E. coli; EIA - enzyme immunoassay; ETEC = enterotoxigenic E. coli; GDH = glutamate dehydrogenase; HUS = hemolytic uremic syndrome; IBS = irritable bowel syndrome; lV = intravenous; NAAT = nucleic acid amplification test; PCR = polymerase chain reaction; STEC = Shiga toxin-producin g E. coli. bEmpiric treatment, with the final choice of the antimicrobial agent to use guided by in vitro susceptibility testing. considered followed by empiric azithromycin treatment. is about 3 days; see Table 46 for clinical findings and postinfec- Microbiologic assessment should guide treatment of chronic tion complications. Stools are visibly bloody in approximately diarrhea. 15'/. of patients. Stool culture and molecular testing can be used Patients with dysentery and a temperature of 37.8 'C for diagnosis; blood cultures can identi$z extraintestinal disease. (foO "f') or less should have microbiologic assessment to guide Diarrhea usually resolves spontaneously. Patients who have therapy. When severe debilitating dysentery is present with severe disease (bloody stools, bacteremia, high fever, or pro- temperatures of 38.3 'C (101 "F) or greater, microbiologic longed [>t week] symptoms) or are immunocompromised assessment should be considered, followed by empiric azithro- should receive antibiotic therapy. When indicated, macrolide mycin treatment; if travel associated, empiric azithromycin therapy is preferred empirically because of increasing fluoro- treatment is recommended. Antimotility agents, such as quinolone resistance. loperamide, are discouraged in patients with inflammatory f,EY POIilT diarrhea (fever, abdominal pain, bloody stools) or Clostridioides dffi cile - associated infection. . CampAlobacter- associated diarrhea usually resolves spontaneously; azithromycin is generally the preferred r(EY POTilTS empiric treatment for those who have severe disease or o Patients with mucoid or bloody diarrhea (dysentery), are immunocompromised. fever, significant abdominal cramping, or suspected sepsis and those who are immunocompromised or require hospitalization should have diagnostic assess- Shigella Infection ment of their stool to guide antimicrobial use. Shigella infection is most commonly spread from person to HVC o Most healthy patients with watery diarrhea of less than person and by consumption of contaminated food or water. 3 days' duration can be treated with supportive care and Fewer than 100 bacteria can cause infection, and the incuba- no diagnostic assessment; when the illness is debilitating tion period is approximately 3 days. Patients typically present and associated with travel, antibiotic therapy with a fluo- with dysentery: crampy abdominal pain, tenesmus, small- roquinolone, azithromycin, or rifaximin is recommended. volume bloody andior mucoid diarrhea and high fever. More serious complications include bacteremia, seizures, and intes- tinal obstruction and perforation; postinfectious sequelae may Ca m pyl ob acte r I nfeqti o n also occur (see Table 46). Routine stool culture and molecular Campylobocter-associated gastroenteritis is usually foodborne, testing can assist with diagnosis. Blood cultures can confirm often secondary to undercooked poultry. The incubation period invasive disease in patients with severe infection. Treatment

considered followed by empiric azithromycin treatment. is about 3 days; see Table 46 for clinical findings and postinfec- Microbiologic assessment should guide treatment of chronic tion complications. Stools are visibly bloody in approximately diarrhea. 15'/. of patients. Stool culture and molecular testing can be used Patients with dysentery and a temperature of 37.8 'C for diagnosis; blood cultures can identi$z extraintestinal disease. (foO "f') or less should have microbiologic assessment to guide Diarrhea usually resolves spontaneously. Patients who have therapy. When severe debilitating dysentery is present with severe disease (bloody stools, bacteremia, high fever, or pro- temperatures of 38.3 'C (101 "F) or greater, microbiologic longed [>t week] symptoms) or are immunocompromised assessment should be considered, followed by empiric azithro- should receive antibiotic therapy. When indicated, macrolide mycin treatment; if travel associated, empiric azithromycin therapy is preferred empirically because of increasing fluoro- treatment is recommended. Antimotility agents, such as quinolone resistance. loperamide, are discouraged in patients with inflammatory f,EY POIilT diarrhea (fever, abdominal pain, bloody stools) or Clostridioides dffi cile - associated infection. . CampAlobacter- associated diarrhea usually resolves spontaneously; azithromycin is generally the preferred r(EY POTilTS empiric treatment for those who have severe disease or o Patients with mucoid or bloody diarrhea (dysentery), are immunocompromised. fever, significant abdominal cramping, or suspected sepsis and those who are immunocompromised or require hospitalization should have diagnostic assess- Shigella Infection ment of their stool to guide antimicrobial use. Shigella infection is most commonly spread from person to HVC o Most healthy patients with watery diarrhea of less than person and by consumption of contaminated food or water. 3 days' duration can be treated with supportive care and Fewer than 100 bacteria can cause infection, and the incuba- no diagnostic assessment; when the illness is debilitating tion period is approximately 3 days. Patients typically present and associated with travel, antibiotic therapy with a fluo- with dysentery: crampy abdominal pain, tenesmus, small- roquinolone, azithromycin, or rifaximin is recommended. volume bloody andior mucoid diarrhea and high fever. More serious complications include bacteremia, seizures, and intes- tinal obstruction and perforation; postinfectious sequelae may Ca m pyl ob acte r I nfeqti o n also occur (see Table 46). Routine stool culture and molecular Campylobocter-associated gastroenteritis is usually foodborne, testing can assist with diagnosis. Blood cultures can confirm often secondary to undercooked poultry. The incubation period invasive disease in patients with severe infection. Treatment 70

lnfectious Gastrointestinal Syndromes with antibiotics is recommended for those with severe illness with severe disease requiring hospitalization. Local antibiotic (those requiring hospitalization, with invasive disease, or with susceptibilities of Salmonello should dictate empiric therapy. complications) and those who are immunocompromised. Treatment may also be recommended when outbreaks occur. KEY POITTS Ciprofloxacin, azithromycin, and ceftriaxone have been used . Nontyphoidal Solmonellaserotypes are the most com- for treatment, but ideally antibiotic susceptibilities should be mon bacterial cause of foodborne illness in the United obtained because of increasing resistance rates. National States; diagnosis is made by stool culture or molecular Antimicrobial Resistance Monitoring System (http: i/www.cdc. testing, and the illness is usually self-limited, although gov/narms) data can help guide empiric decisions. bacteremia with extraintestinal infection may occur. o Most uncomplicated Sqlmonello infections in adults HVC rEY POI ]II younger than 50 years resolve within l week and . In patients with Shigella infection, treatment with anti- require only supportive care; when empiric treatment is biotic agents is recommended for those with severe ill- indicated for those with more severe or invasive disease, ness and those who are immunocompromised. fluoroquinolones (such as ciprofloxacin) are most likely to be effective.

with antibiotics is recommended for those with severe illness with severe disease requiring hospitalization. Local antibiotic (those requiring hospitalization, with invasive disease, or with susceptibilities of Salmonello should dictate empiric therapy. complications) and those who are immunocompromised. Treatment may also be recommended when outbreaks occur. KEY POITTS Ciprofloxacin, azithromycin, and ceftriaxone have been used . Nontyphoidal Solmonellaserotypes are the most com- for treatment, but ideally antibiotic susceptibilities should be mon bacterial cause of foodborne illness in the United obtained because of increasing resistance rates. National States; diagnosis is made by stool culture or molecular Antimicrobial Resistance Monitoring System (http: i/www.cdc. testing, and the illness is usually self-limited, although gov/narms) data can help guide empiric decisions. bacteremia with extraintestinal infection may occur. o Most uncomplicated Sqlmonello infections in adults HVC rEY POI ]II younger than 50 years resolve within l week and . In patients with Shigella infection, treatment with anti- require only supportive care; when empiric treatment is biotic agents is recommended for those with severe ill- indicated for those with more severe or invasive disease, ness and those who are immunocompromised. fluoroquinolones (such as ciprofloxacin) are most likely to be effective. Salmonella Infection Salmonello infections can be typhoidal or nontyphoidal. The Escherichia coli I nfeqtion typhoidal types cause enteric fever, a syndrome consisting of Although Escherichiacoliare normal inhabitants of the intes- fever, abdominal pain, rash (see Travel Medicine), hepato- tinal microbiome, some strains can become enteropathogenic splenomegaly, and relative bradycardia. This type of infection (Table a7). is uncommon in the United States, with most affected per- Enterotoxigenic E. coli infection (ETEC) is the most com- sons traveling to endemic areas and ingesting contaminated mon cause of travelers' diarrhea. ETEC results from ingestion water or food. In contrast, nontyphoidal serotypes are the of water or food contaminated with stool and has an incuba- most common bacterial cause of foodborne illness in the tion period of 1 to 3 days. Enterotoxins cause watery diarrhea United States. with abdominal cramping, nausea, and low-grade or no fever. Nontyphoidal Solmonello infection usually results from Usually self-limiting, the illness resolves after approximately ingesting fecally contaminated water or food of animal origin, including poultry beef, eggs, and milk. Contact with infected animais (including pet reptiles, amphibians, and poultry) is a TABLE 47. Diarrheagenic Strains o{ Escherichia coli less common mode of transmission. The incubation period is Strain Epidemiology ClinicalFindings usually less than 3 days, and symptoms typically include Enteroaggregative Diarrhea in Watery diarrhea, crampy abdominal pain, fever, diarrhea (not usually visibly E. coli (EAEC) travelers, young fever typically bloody), headache, nausea, and vomiting. Stool culture or children, and absent molecular testing can be diagnostic. Illness is usually self- patients with HIV infection limited, although bacteremia with extraintestinal infection (involving vascular endothelium, joints, or meninges) may Enteroinvasive Allages, primarily lnflammatory E. coli(EIEC) in developing diarrhea occur. Salmonello osteomyelitis is classically associated with countries (dysentery)with sickle cell disease. Severe invasive disease is more likely in fever, abdominal pain infants, older adults, patients with cell-mediated immunode- ficiency, and patients with hypochlorhydria. Postinfection Enteropathogenic Sporadic, Nausea, vomiting, E. coli(EPEC) occasionally malnutrition complications may also occur (see Table 46). persistent (when chronic) Most uncomplicated Solmonello infections in adults diarrhea in young younger than 50 years resolve within l week and require only children supportive care. Antibiotics are typically reserved for patients Enterotoxigenic Diarrhea in Watery diarrhea, E. coli(ETEC) travelers, fever typically with more serious illness (including severe diarrhea requiring absent or low foodborne hospitalization, bacteremia, high fever, or sepsis) and those at outbreaks grade high risk for severe complicated invasive disease (including Foodborne Bloody stools, Shiga toxin- infants, patients )50 years, or those with prosthetic materials, producing E. coli outbreaks progression to significant atherosclerotic disease, or immunocompromising (sTEC)/ (associated with hemolytic uremic Enterohemorrhagic beef and other syndrome, fever conditions). Fluoroquinolones (such as ciprofloxacin) are most contaminated typically absent E. coli(EHEC) likely to be effective, but azithromycin and trimethoprim- food), person-to- sulfamethoxazole are potentially active empiric agents. A fluo- person, and zoonotic roquinolone or third-generation cephalosporin (such as transmission ceftriaxone) are often initiated as empiric therapy for patients

Salmonella Infection Salmonello infections can be typhoidal or nontyphoidal. The Escherichia coli I nfeqtion typhoidal types cause enteric fever, a syndrome consisting of Although Escherichiacoliare normal inhabitants of the intes- fever, abdominal pain, rash (see Travel Medicine), hepato- tinal microbiome, some strains can become enteropathogenic splenomegaly, and relative bradycardia. This type of infection (Table a7). is uncommon in the United States, with most affected per- Enterotoxigenic E. coli infection (ETEC) is the most com- sons traveling to endemic areas and ingesting contaminated mon cause of travelers' diarrhea. ETEC results from ingestion water or food. In contrast, nontyphoidal serotypes are the of water or food contaminated with stool and has an incuba- most common bacterial cause of foodborne illness in the tion period of 1 to 3 days. Enterotoxins cause watery diarrhea United States. with abdominal cramping, nausea, and low-grade or no fever. Nontyphoidal Solmonello infection usually results from Usually self-limiting, the illness resolves after approximately ingesting fecally contaminated water or food of animal origin, including poultry beef, eggs, and milk. Contact with infected animais (including pet reptiles, amphibians, and poultry) is a TABLE 47. Diarrheagenic Strains o{ Escherichia coli less common mode of transmission. The incubation period is Strain Epidemiology ClinicalFindings usually less than 3 days, and symptoms typically include Enteroaggregative Diarrhea in Watery diarrhea, crampy abdominal pain, fever, diarrhea (not usually visibly E. coli (EAEC) travelers, young fever typically bloody), headache, nausea, and vomiting. Stool culture or children, and absent molecular testing can be diagnostic. Illness is usually self- patients with HIV infection limited, although bacteremia with extraintestinal infection (involving vascular endothelium, joints, or meninges) may Enteroinvasive Allages, primarily lnflammatory E. coli(EIEC) in developing diarrhea occur. Salmonello osteomyelitis is classically associated with countries (dysentery)with sickle cell disease. Severe invasive disease is more likely in fever, abdominal pain infants, older adults, patients with cell-mediated immunode- ficiency, and patients with hypochlorhydria. Postinfection Enteropathogenic Sporadic, Nausea, vomiting, E. coli(EPEC) occasionally malnutrition complications may also occur (see Table 46). persistent (when chronic) Most uncomplicated Solmonello infections in adults diarrhea in young younger than 50 years resolve within l week and require only children supportive care. Antibiotics are typically reserved for patients Enterotoxigenic Diarrhea in Watery diarrhea, E. coli(ETEC) travelers, fever typically with more serious illness (including severe diarrhea requiring absent or low foodborne hospitalization, bacteremia, high fever, or sepsis) and those at outbreaks grade high risk for severe complicated invasive disease (including Foodborne Bloody stools, Shiga toxin- infants, patients )50 years, or those with prosthetic materials, producing E. coli outbreaks progression to significant atherosclerotic disease, or immunocompromising (sTEC)/ (associated with hemolytic uremic Enterohemorrhagic beef and other syndrome, fever conditions). Fluoroquinolones (such as ciprofloxacin) are most contaminated typically absent E. coli(EHEC) likely to be effective, but azithromycin and trimethoprim- food), person-to- sulfamethoxazole are potentially active empiric agents. A fluo- person, and zoonotic roquinolone or third-generation cephalosporin (such as transmission ceftriaxone) are often initiated as empiric therapy for patients 71

I nfectious Gastrointestinal Syndromes 4 days. Hydration and empiric antibiotic therapy with fluoro- enrichment conditions are applied. Uncomplicated gastroin- quinolones, azithromycin, or rifaximin are recommended in testinal illness in healthy, immunocompetent adults does not travelers with ETEC when symptoms restrict activities. require treatment. When treatment is indicated, a fluoroquin- Enterohemorrhagic E. coli (EHEC) strains, most com- olone (such as ciprofloxacin) is recommended' If disease is monly -O!57:H7, produce a Shiga toxin (i.e., Shiga-toxin pro- severe, empiric intravenous ceftriaxone with an aminoglyco- ducing E. coli, or STEC) that can cause hemorrhagic colitis. side like gentamicin is used. These bacteria are found in cow intestines and are transmitted KEY PO I T{TS by ingesting undercooked hamburgers or fecally contami- o Most Yersiniaspecies diarrheal illness is caused by nated food and water; fecal-oral transmission through expo- Yersinia enterocolitico, usually after ingestion of contam- sure to infected animals is also possible. The incubation period inated food, particularly undercooked pork; the diagno- is 3 to 4 days, and patients typically have visibly bloody diar- sis is confirmed by molecular testing of stool or by cul- rhea, crampy abdominal pain, and no fever, the latter a distin- ture of stool, blood, a throat swab, or infected tissue. guishing feature from other causes of bloody diarrhea. Alerting the laboratory is recommended so that appropriate media, . When treatment is indicated, a fluoroquinolone (such antigen testing, and Shiga toxin assays can be performed. as ciprofloxacin) is recommended; if disease is severe,

4 days. Hydration and empiric antibiotic therapy with fluoro- enrichment conditions are applied. Uncomplicated gastroin- quinolones, azithromycin, or rifaximin are recommended in testinal illness in healthy, immunocompetent adults does not travelers with ETEC when symptoms restrict activities. require treatment. When treatment is indicated, a fluoroquin- Enterohemorrhagic E. coli (EHEC) strains, most com- olone (such as ciprofloxacin) is recommended' If disease is monly -O!57:H7, produce a Shiga toxin (i.e., Shiga-toxin pro- severe, empiric intravenous ceftriaxone with an aminoglyco- ducing E. coli, or STEC) that can cause hemorrhagic colitis. side like gentamicin is used. These bacteria are found in cow intestines and are transmitted KEY PO I T{TS by ingesting undercooked hamburgers or fecally contami- o Most Yersiniaspecies diarrheal illness is caused by nated food and water; fecal-oral transmission through expo- Yersinia enterocolitico, usually after ingestion of contam- sure to infected animals is also possible. The incubation period inated food, particularly undercooked pork; the diagno- is 3 to 4 days, and patients typically have visibly bloody diar- sis is confirmed by molecular testing of stool or by cul- rhea, crampy abdominal pain, and no fever, the latter a distin- ture of stool, blood, a throat swab, or infected tissue. guishing feature from other causes of bloody diarrhea. Alerting the laboratory is recommended so that appropriate media, . When treatment is indicated, a fluoroquinolone (such antigen testing, and Shiga toxin assays can be performed. as ciprofloxacin) is recommended; if disease is severe, Hemolytic uremic syndrome develops in less than 10% of empiric intravenous ceftriaxone with an aminoglyco- patients infected with EHEC and manifests as microangio- side like gentamicin is used. pathic hemolytic anemia, thrombocytopenia, and kidney injury. Treatment is primarily supportive; antibiotics and anti- motility agents may increase the risk of developing hemolytic Vibrio lnfection uremic syndrome and do not appear to shorten infection In the United States, Vibrio parahaemolyticus is the most duration. common Vibrio species to cause gastrointestinal illness, I(EY PO I ilT5 usually after consumption of undercooked oysters and other HVC o Enterotoxigenic Escherichia coli infection is usually a shellfish. The incubation period is about 2 days; typically self-limiting illness that resolves without treatment reported presenting symptoms are diarrhea (can be bloody), after approximately 4 days; hydration and empiric anti- fever, nausea or emesis, and crampy abdominal pain. biotic therapy with fluoroquinolones, azithromycin, or Septicemia can develop in patients who have liver disease rifaximin are recommended in travelers when symp- and may lead to secondary necrotizing skin infections. toms restrict activities. Severe noninvasive gastrointestinal illness can be treated with doxycycline, although fluoroquinolones and mac- HVC o Enterohemorrhagic Escherichia coli strains produce a rolides are alternatives. Patients with septicemia require Shiga toxin that can cause hemorrhagic colitis; treat- more aggressive combination therapy, typically with doxycy- ment is primarily supportive because antibiotics and cline plus ceftriaxone. antimotility agents may increase the risk of developing hemolytic uremic syndrome and do not appear to t(EY POt l{TS shorten infection duration. . Vibrio parahaemolyticus can cause septicemia and necrotizing skin infections in patients who have liver disease. Yersinia Infestion o Severe noninvasive Vibrio parahaemolyticus gastroin- Most Yersinio species diarrheal illness is caused by Yersinia testinal illness is treated with doxycycline, although enterocolitico, usually after ingestion of contaminated food, fluoroquinolones and macrolides are alternatives. particularly undercooked pork. Patients with iron overload states, including hemochromatosis, are at increased risk for infection (including bacteremia) owing to the siderophilic characteristics of Yersinia species. The incubation period is Clostri dioid es difficile I nfection approximately 5 days, and patients typically have fever, Clostridioides dfficile is the leading cause of hospital-acquired abdominal pain, diarrhea (possibly bloody), and (sometimes) infectious diarrhea and results from fecal-oral transmission. nausea and emesis. The organism is drawn to lymphoid tissue The number of these infections reported in the United States (including tonsillar tissue and mesenteric lymph nodes), increased significantly beginning in 2000, owing in large part which results in pharyngitis or right lower-quadrant pain to the emergence of a hypervirulent strain associated with mimicking appendicitis. Postinfection complications may fluoroquinolone use, but recent estimates suggest declining occur (see Table a6). The diagnosis is confirmed by stool disease burden. Risk factors for infection include exposure to molecular testing or culture of stool, blood, a throat swab, or antibiotic and chemotherapeutic agents, older age, severe infected tissue; the testing laboratory should be alerted when underlying comorbidities, presence of inflammatory bowel Yersinia infection is suspected so that optimal media and disease, solid organ transplantation, gastrointestinal surgery

Hemolytic uremic syndrome develops in less than 10% of empiric intravenous ceftriaxone with an aminoglyco- patients infected with EHEC and manifests as microangio- side like gentamicin is used. pathic hemolytic anemia, thrombocytopenia, and kidney injury. Treatment is primarily supportive; antibiotics and anti- motility agents may increase the risk of developing hemolytic Vibrio lnfection uremic syndrome and do not appear to shorten infection In the United States, Vibrio parahaemolyticus is the most duration. common Vibrio species to cause gastrointestinal illness, I(EY PO I ilT5 usually after consumption of undercooked oysters and other HVC o Enterotoxigenic Escherichia coli infection is usually a shellfish. The incubation period is about 2 days; typically self-limiting illness that resolves without treatment reported presenting symptoms are diarrhea (can be bloody), after approximately 4 days; hydration and empiric anti- fever, nausea or emesis, and crampy abdominal pain. biotic therapy with fluoroquinolones, azithromycin, or Septicemia can develop in patients who have liver disease rifaximin are recommended in travelers when symp- and may lead to secondary necrotizing skin infections. toms restrict activities. Severe noninvasive gastrointestinal illness can be treated with doxycycline, although fluoroquinolones and mac- HVC o Enterohemorrhagic Escherichia coli strains produce a rolides are alternatives. Patients with septicemia require Shiga toxin that can cause hemorrhagic colitis; treat- more aggressive combination therapy, typically with doxycy- ment is primarily supportive because antibiotics and cline plus ceftriaxone. antimotility agents may increase the risk of developing hemolytic uremic syndrome and do not appear to t(EY POt l{TS shorten infection duration. . Vibrio parahaemolyticus can cause septicemia and necrotizing skin infections in patients who have liver disease. Yersinia Infestion o Severe noninvasive Vibrio parahaemolyticus gastroin- Most Yersinio species diarrheal illness is caused by Yersinia testinal illness is treated with doxycycline, although enterocolitico, usually after ingestion of contaminated food, fluoroquinolones and macrolides are alternatives. particularly undercooked pork. Patients with iron overload states, including hemochromatosis, are at increased risk for infection (including bacteremia) owing to the siderophilic characteristics of Yersinia species. The incubation period is Clostri dioid es difficile I nfection approximately 5 days, and patients typically have fever, Clostridioides dfficile is the leading cause of hospital-acquired abdominal pain, diarrhea (possibly bloody), and (sometimes) infectious diarrhea and results from fecal-oral transmission. nausea and emesis. The organism is drawn to lymphoid tissue The number of these infections reported in the United States (including tonsillar tissue and mesenteric lymph nodes), increased significantly beginning in 2000, owing in large part which results in pharyngitis or right lower-quadrant pain to the emergence of a hypervirulent strain associated with mimicking appendicitis. Postinfection complications may fluoroquinolone use, but recent estimates suggest declining occur (see Table a6). The diagnosis is confirmed by stool disease burden. Risk factors for infection include exposure to molecular testing or culture of stool, blood, a throat swab, or antibiotic and chemotherapeutic agents, older age, severe infected tissue; the testing laboratory should be alerted when underlying comorbidities, presence of inflammatory bowel Yersinia infection is suspected so that optimal media and disease, solid organ transplantation, gastrointestinal surgery 72

I nfectious Gastrointestinal Synd romes TAS{-# 48. Treatment of Clostridioides difficile lnfection" Severity of Treatment Disease Nonsevere Vancomycin,l25 mg fourtimes daily PO x 10 d or Fidaxomicin, 200 mg twice daily PO x 10 d lf neither oral vancomycin or fidaxomicin is available (or both are contraindicated), metronidazole, 500 mg three times daily PO x 10d Severe Vancomycin, 125 mg four times daily PO x 1 0 d or Fidaxomicin, 200 mg twice daily PO x 10 d Fulminant Vancomycin, 500 mg fourtimes daily PO or by NGl, plus metronidazole,500 mg every 8 h lV When ileus is present, consideration of vancomycin PR at a dose of 500 mg in approximately 100 mL normal saline every 6 h lV = intravenously; NGT = nasogastric tube; PO = by mouth; PR = per rectum. alnitial presentation.

TAS{-# 48. Treatment of Clostridioides difficile lnfection" Severity of Treatment Disease Nonsevere Vancomycin,l25 mg fourtimes daily PO x 10 d or Fidaxomicin, 200 mg twice daily PO x 10 d lf neither oral vancomycin or fidaxomicin is available (or both are contraindicated), metronidazole, 500 mg three times daily PO x 10d Severe Vancomycin, 125 mg four times daily PO x 1 0 d or Fidaxomicin, 200 mg twice daily PO x 10 d Fulminant Vancomycin, 500 mg fourtimes daily PO or by NGl, plus metronidazole,500 mg every 8 h lV When ileus is present, consideration of vancomycin PR at a dose of 500 mg in approximately 100 mL normal saline every 6 h lV = intravenously; NGT = nasogastric tube; PO = by mouth; PR = per rectum. alnitial presentation. FIGURE 32, Clostridioides difficile colitis showing exudative pseudomembranes. institutional stool submission criteria are strictly met (no laxa- tive use; more than three new-onset, unformed, and unex- plained stools in 24 hours). In this setting, NAAT alone is and (possibly) gastric acid suppression with proton pump sufficient. Combined EIA tests for GDH plus toxin (discordant inhibitors. Antibiotic stewardship is paramount in reducing results require NAAT testing) or NAAT plus toxin should be incidence of infection, and hand washing with soap and water performed in those institutional settings not adherent to the is the gold standard for infection control; alcohol-based gels do specifled criteria for stool submission. not eliminate spores. Asymptomatic colonization can occur; for those with In infected patients, the antibiotic agent associated with pathologic infection, the incubation period can be as long as 3 the infection should be stopped if possible. Treatment is dic- tated by severiff of disease (Table 48). Severe disease is defined months after perturbation of the intestinal flora with antibi- clinically by a leukocyte count of 15,000/pL (15 x 10e/L) or otic agents. Community-acquired infections without previous greater or a serum creatinine level of 1.5 mgldl. (133 pmol/L) or exposure to health care settings, antibiotic agents, or both have greater. Oral vancomycin or fidaxomicin for 10 days is recom- been increasingly reported. mended for severe and nonsevere disease. Oral metronidazole C. dfficile produces an enterotoxin (toxin A) and a cyto- can be used for nonsevere disease if neither of these agents is toxin (toxin B) that are pathogenic. Symptomatic patients available. Fulminant disease includes associated shock, hypo- typically have watery diarrhea (rarely bloody), crampy tension, toxic megacolon, or ileus. Higher-dose oral or nasogas- abdominal pain, malaise, and sometimes nausea and fever. Abnormal laboratory study findings are nonspecific but can tric vancomycin, intravenous metronidazole, and (possibly) vancomycin enema (when ileus is present) are recommended. include marked leukocytosis, an elevated serum creatinine Patients with fulminant disease warrant surgical evaluation. level, and hypoalbuminemia. Radiographic imaging, also Recurrent infection is reported in as many as 25olo of patients, nonspecific, may demonstrate colonic wall thickening, and treatment recommendations are provided in Table 49. mucosal edema, fat stranding, and megacolon. Colonoscopy, Studies have shown that fecal microbiota transplantation is effec- although not a routine diagnostic modality, may show pseu- tive in the management of patients with multiple recurrences. domembranes (Figure 32). Retesting stool for C. dfficile after treatment for evidence of cure Diagnosis is usually established by testing unformed in patients who have no symptoms is not recommended. stools from persons not taking laxatives who have unexplained new-onset diarrhea occurring three or more times daily. f,EY POIilI5 Although highly specific and rapid, enzyme immunoassay . Clostndioides difficileis the leading cause of hospital- HVC (EIA) testing for presence of toxin A or B lacks sensitivity. EIA acquired infectious diarrhea; antibiotic stewardship is para- testing for glutamate dehydrogenase (GDH), an antigenic pro- mount in reducing incidence of infection, and hand wash- tein present in all C. dfficile isolates, is sensitive but lacks ingwith soap andwater is importantto eliminate spores. specificity. Nucleic acid amplification testing (NAAT) for C. (Continued) dfficile toxin genes is sensitive and specific if appropriate

FIGURE 32, Clostridioides difficile colitis showing exudative pseudomembranes. institutional stool submission criteria are strictly met (no laxa- tive use; more than three new-onset, unformed, and unex- plained stools in 24 hours). In this setting, NAAT alone is and (possibly) gastric acid suppression with proton pump sufficient. Combined EIA tests for GDH plus toxin (discordant inhibitors. Antibiotic stewardship is paramount in reducing results require NAAT testing) or NAAT plus toxin should be incidence of infection, and hand washing with soap and water performed in those institutional settings not adherent to the is the gold standard for infection control; alcohol-based gels do specifled criteria for stool submission. not eliminate spores. Asymptomatic colonization can occur; for those with In infected patients, the antibiotic agent associated with pathologic infection, the incubation period can be as long as 3 the infection should be stopped if possible. Treatment is dic- tated by severiff of disease (Table 48). Severe disease is defined months after perturbation of the intestinal flora with antibi- clinically by a leukocyte count of 15,000/pL (15 x 10e/L) or otic agents. Community-acquired infections without previous greater or a serum creatinine level of 1.5 mgldl. (133 pmol/L) or exposure to health care settings, antibiotic agents, or both have greater. Oral vancomycin or fidaxomicin for 10 days is recom- been increasingly reported. mended for severe and nonsevere disease. Oral metronidazole C. dfficile produces an enterotoxin (toxin A) and a cyto- can be used for nonsevere disease if neither of these agents is toxin (toxin B) that are pathogenic. Symptomatic patients available. Fulminant disease includes associated shock, hypo- typically have watery diarrhea (rarely bloody), crampy tension, toxic megacolon, or ileus. Higher-dose oral or nasogas- abdominal pain, malaise, and sometimes nausea and fever. Abnormal laboratory study findings are nonspecific but can tric vancomycin, intravenous metronidazole, and (possibly) vancomycin enema (when ileus is present) are recommended. include marked leukocytosis, an elevated serum creatinine Patients with fulminant disease warrant surgical evaluation. level, and hypoalbuminemia. Radiographic imaging, also Recurrent infection is reported in as many as 25olo of patients, nonspecific, may demonstrate colonic wall thickening, and treatment recommendations are provided in Table 49. mucosal edema, fat stranding, and megacolon. Colonoscopy, Studies have shown that fecal microbiota transplantation is effec- although not a routine diagnostic modality, may show pseu- tive in the management of patients with multiple recurrences. domembranes (Figure 32). Retesting stool for C. dfficile after treatment for evidence of cure Diagnosis is usually established by testing unformed in patients who have no symptoms is not recommended. stools from persons not taking laxatives who have unexplained new-onset diarrhea occurring three or more times daily. f,EY POIilI5 Although highly specific and rapid, enzyme immunoassay . Clostndioides difficileis the leading cause of hospital- HVC (EIA) testing for presence of toxin A or B lacks sensitivity. EIA acquired infectious diarrhea; antibiotic stewardship is para- testing for glutamate dehydrogenase (GDH), an antigenic pro- mount in reducing incidence of infection, and hand wash- tein present in all C. dfficile isolates, is sensitive but lacks ingwith soap andwater is importantto eliminate spores. specificity. Nucleic acid amplification testing (NAAT) for C. (Continued) dfficile toxin genes is sensitive and specific if appropriate 73

lnfectious Gastrointestinal Syndromes TABLE 49. Treatment of Recurrent Clostridioides difficile I(EY POIlIT lnfection o Noroviruses are the most common cause of gastroen- First recurrence/ Vancomycin,l25 mg fourtimes daily PO teritis in the United States; viral shedding persists as second episode x 10 d, if metronidazole used for initial long as 2 weeks after symptom resolution, which con- episode or tributes to high infectivity. Prolonged tapered and pulsed vancomycin if standard regimen was used for initial episode (that is, vancomycin, 125 mg four times daily PO x 1 0 d, then Parasitic Infection 125 mg twice daily PO x 7 d, then 125 mg Parasitic infection should be considered in patients with every 2 or 3 d PO for 2-8 wk)or chronic diarrhea. Immunosuppressed persons are at increased Fidaxomicin, 200 mg twice daily PO x 10 d, if vancomycin PO was used for the initial risk for more chronic and severe infection. episode Second and Prolonged tapered and pulsed Giardia lamblia lnfection subsequent vancomycin PO (see above)or Giardia lamblia is the most common parasitic pathogen in the recurrence(s)/ Vancomycin,l25 mg fourtimes daily PO United States. Cysts from infected animals are excreted in stool third and x 10 d, followed by rifaximin,400 mg into reservoirs of fresh water, and subsequent ingestion of con su bseq uent three times daily PO x20 d or episodes taminated water (or food) can lead to human infection. F'rdaxomicin, 200 mg twice daily PO x 10 d Secondary person-to-person transmission is also possible. Persons at risk for infection include outdoor travelers, children Fecal microbiota transplantation (after two recurrences treated with appropriate in day care centers, immunocompromised hosts (particularly antibiotics) those with humoral immunodeficienry), and persons engaged in sexual activity that includes oral-anal contact. The incubation PO = by mouth. period ranges from 1 to 3 weeks. More than half of infected patients are asymptomatic; however, if present, symptoms, can (EY POlt{IS (continud) last for several weeks until spontaneously resolving (see Table 46). . Nucleic acid amplification testing for Clostridioides dif- Chronic infection may develop, particularly in persons with ficile toxin genes is rapid, highly sensitive, and specific; hypogammaglobulinemia. Immunoassays for antigen detection enzyme immunoassay testing for presence of toxin A or and molecular testing of stool are more sensitive than stool B is highly specific and rapid but lacks sensitivity, and microscopy for confirming the diagnosis. Treatment is recom- enzyme immunoassay testing for presence of glutamate mended for symptomatic patients; metronidazole, tinidazole, or dehydrogenase is quite sensitive but lacks specificity. nitazoxanide can be used. Postinfection lactose intolerance or IBS o Treatment of an initial Clostridioides dfficile infection may be mistaken fbr recurrent or resistant Giardiainfection. is dictated by disease severity, with nonsevere disease I(EY POIilIS treated with oral vancomycin or fidaxomicin, severe o Parasitic infection should be considered in patients disease treated with oral vancomycin or fidaxomicin, with chronic diarrhea. and fulminant disease treated with higher-dose oral vancomycin, intravenous metronidazole, and (when o More than half of patients infected with Giordialam- ileus is present) vancomycin enema. bliaare asymptomatic; in symptomatic patients, treat- ment with metronidazole, tinidazole, or nitazoxanide can be used. Viral Gastroenteritis o Postinfection lactose intolerance or irritable bowel syn- Viruses are responsible for acute gastroenteritis in most drome may be mistaken for recurrent or resistant patients. Rotavirus infects young children, and noroviruses, Giardia infection. which are the most common cause of gastroenteritis in the United States, affect all ages. Norovirus outbreaks on cruise Cryptosporidiu m I nfection ships and in schools and other institutionalized settings are Cryptosporidium species can infect humans and other mam- well documented. Transmission from person to person is pri- mals. Infection occurs after consumption of fecally contami- marily fecal oral. Infection can develop after ingestion of fewer nated water or food or through close person-to person or than 100 viral particles. The incubation period is typically less animal-to-person transmission. Municipal water supplies and than 2 days, and infected patients usually have self-limited swimming pools can be a source of infection because the watery diarrhea, nausea, vomiting, and fever. Treatment is thick-walled oocysts are chlorine resistant and can evade fil supportive. Diagnostic molecular testing is available. Viral tration. It is highly infectious, and ingestion of fewer than 50 shedding persists for as long as 2 weeks after symptom resolu- oocysts may result in infection. The incubation period is tion, which contributes to its high infectivity. 7 days. Clinical findings are described in Table 46. Symptoms

TABLE 49. Treatment of Recurrent Clostridioides difficile I(EY POIlIT lnfection o Noroviruses are the most common cause of gastroen- First recurrence/ Vancomycin,l25 mg fourtimes daily PO teritis in the United States; viral shedding persists as second episode x 10 d, if metronidazole used for initial long as 2 weeks after symptom resolution, which con- episode or tributes to high infectivity. Prolonged tapered and pulsed vancomycin if standard regimen was used for initial episode (that is, vancomycin, 125 mg four times daily PO x 1 0 d, then Parasitic Infection 125 mg twice daily PO x 7 d, then 125 mg Parasitic infection should be considered in patients with every 2 or 3 d PO for 2-8 wk)or chronic diarrhea. Immunosuppressed persons are at increased Fidaxomicin, 200 mg twice daily PO x 10 d, if vancomycin PO was used for the initial risk for more chronic and severe infection. episode Second and Prolonged tapered and pulsed Giardia lamblia lnfection subsequent vancomycin PO (see above)or Giardia lamblia is the most common parasitic pathogen in the recurrence(s)/ Vancomycin,l25 mg fourtimes daily PO United States. Cysts from infected animals are excreted in stool third and x 10 d, followed by rifaximin,400 mg into reservoirs of fresh water, and subsequent ingestion of con su bseq uent three times daily PO x20 d or episodes taminated water (or food) can lead to human infection. F'rdaxomicin, 200 mg twice daily PO x 10 d Secondary person-to-person transmission is also possible. Persons at risk for infection include outdoor travelers, children Fecal microbiota transplantation (after two recurrences treated with appropriate in day care centers, immunocompromised hosts (particularly antibiotics) those with humoral immunodeficienry), and persons engaged in sexual activity that includes oral-anal contact. The incubation PO = by mouth. period ranges from 1 to 3 weeks. More than half of infected patients are asymptomatic; however, if present, symptoms, can (EY POlt{IS (continud) last for several weeks until spontaneously resolving (see Table 46). . Nucleic acid amplification testing for Clostridioides dif- Chronic infection may develop, particularly in persons with ficile toxin genes is rapid, highly sensitive, and specific; hypogammaglobulinemia. Immunoassays for antigen detection enzyme immunoassay testing for presence of toxin A or and molecular testing of stool are more sensitive than stool B is highly specific and rapid but lacks sensitivity, and microscopy for confirming the diagnosis. Treatment is recom- enzyme immunoassay testing for presence of glutamate mended for symptomatic patients; metronidazole, tinidazole, or dehydrogenase is quite sensitive but lacks specificity. nitazoxanide can be used. Postinfection lactose intolerance or IBS o Treatment of an initial Clostridioides dfficile infection may be mistaken fbr recurrent or resistant Giardiainfection. is dictated by disease severity, with nonsevere disease I(EY POIilIS treated with oral vancomycin or fidaxomicin, severe o Parasitic infection should be considered in patients disease treated with oral vancomycin or fidaxomicin, with chronic diarrhea. and fulminant disease treated with higher-dose oral vancomycin, intravenous metronidazole, and (when o More than half of patients infected with Giordialam- ileus is present) vancomycin enema. bliaare asymptomatic; in symptomatic patients, treat- ment with metronidazole, tinidazole, or nitazoxanide can be used. Viral Gastroenteritis o Postinfection lactose intolerance or irritable bowel syn- Viruses are responsible for acute gastroenteritis in most drome may be mistaken for recurrent or resistant patients. Rotavirus infects young children, and noroviruses, Giardia infection. which are the most common cause of gastroenteritis in the United States, affect all ages. Norovirus outbreaks on cruise Cryptosporidiu m I nfection ships and in schools and other institutionalized settings are Cryptosporidium species can infect humans and other mam- well documented. Transmission from person to person is pri- mals. Infection occurs after consumption of fecally contami- marily fecal oral. Infection can develop after ingestion of fewer nated water or food or through close person-to person or than 100 viral particles. The incubation period is typically less animal-to-person transmission. Municipal water supplies and than 2 days, and infected patients usually have self-limited swimming pools can be a source of infection because the watery diarrhea, nausea, vomiting, and fever. Treatment is thick-walled oocysts are chlorine resistant and can evade fil supportive. Diagnostic molecular testing is available. Viral tration. It is highly infectious, and ingestion of fewer than 50 shedding persists for as long as 2 weeks after symptom resolu- oocysts may result in infection. The incubation period is tion, which contributes to its high infectivity. 7 days. Clinical findings are described in Table 46. Symptoms 74

lnfections in Transplant Recipients usually last less than 2 weeks before spontaneously resolving Cyclospora lnfection in immunocompetent hosts. Immunocompromised patients, Cyclospora infections are typically acquired after consump- in particular patients with AIDS, can develop serious and pro tion of food or water that is fecally contaminated with longed infection. Diagnosis from stool can be pursued micro- Cyclospora oocysts. In the United States, many of these infec- scopically by visualization of oocysts with modified acid-fast tions have been traced to imported fresh produce from tropical staining, EIA or direct immunofluorescent antibody testing, or and subtropical areas or have occurred in travelers to endemic molecular testing. Treatment for immunocompetent patients areas. The incubation period is approximately 1 week. usually consists of supportive care. When antimicrobial agents Symptoms can last for several weeks and may be more pro are considered for severe or prolonged infection, nitazoxanide nounced in HlV-infected patients (Table 46). is recommended. In HlV-infected patients, antiretroviral ther- apy is most effective in resolving infection. I(EY POIl{T o Cyclosporo infection is typically diagnosed microscopi, I(EY POIilTS cally by visualization of oocysts with modified acid-fast o Municipal water supplies and swimming pools can be a staining, microscopy with ultraviolet fluorescence, or source of Crgptosporidium infection. molecular testing; trimethoprim-sulfamethoxazole is o Microscopic visualization of oocysts in stool using modi- recommended for treatment of symptomatic infection. fied acid-fast staining, erzyme immunoassay or direct immunofluorescent antibody testing, or molecular testing can provide a diagnosis of Cryptosporidiuminfection. o Treatmentof Cryptosporidium infection consists of I nfections in Transplant supportive care for most immunocompetent hosts or nitazoxanide for severe or prolonged infection; antiret- Recipients roviral therapy is most effective in resolving infection in lntroduction HlV-infected patients. The occurrence of solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) procedures Amebiasis continues to increase, as do long term survival rates owing to Entamoeba histolytico is responsible for amebiasis. In the improved management of rejection and decreased complica- United States, most infections are diagnosed in travelers return- tions. With more patients living longer after transplantation, ing from visits to unsanitary tropical or developing countries, awareness of principles involved in the recognition and pre- immigrants from these areas, persons in institutionalized set- vention of infection in transplant recipients remains impor- tings, or those who practice oral-anal sex. Amebiasis is highly tant for physicians who are not transplant specialists. infectious, with ingestion of only a small number of infective Despite improvements in immunosuppression and anti- cysts needed for infection. The incubation period is 2 to 4 weeks. microbial therapy, infection remains a significant cause of Clinical findings are described in Table 46. Colonic perforation, morbidity and mortality after SOT and HSCT. Infection is the peritonitis, and death may complicate more fulminant infec most common cause of death in the first year after SOT. tions. Risk factors for severe infection in adults include immu- Additionally, the interaction of the immune system and infec- nodeficiency. Microscopic visualization of cysts or trophozoites, tion is bidirectional; although immune suppression to prevent stool antigen immunoassay testing, stool molecular testing, and rejection increases risk of infection, infection also raises the serologic antibody testing can provide a diagnosis, although the risk of rejection. latter does not distinguish current from remote infection. Treatment is recommended for all infected patients. In sympto matic patients, treatment with metronidazole or tinidazole is Antirejection Drugs in recommended initially for parasitic clearance followed by an Transplant Recipients intraluminal amebicide, such as paromomycin or diloxanide, Success after transplantation depends on modulating the for cyst clearance. In asymptomatic infections, an intraluminal immune system to prevent organ rejection in SOT and to mini- agent for eradication of cysts is recommended. mize graft-versus-host disease (GVHD) in allogeneic HSCT. IEY POIl{I Antirejection regimens involve multiple agents (TaUte 5O)with o Treatment is recommended for all patients with amebi- different mechanisms of action, which are chosen to minimize overlapping toxicities. After SOI an induction and mainte- asis; for symptomatic patients, metronidazole or tinida- nance strate$/ is applied; immunosuppression is most inten- zole is recommended initially for parasitic clearance fol- sive in the first month after transplantation and often includes lowed by an intraluminal amebicide for cyst clearance, lymphocyte depletion therapy. Immunosuppression may and for asymptomatic patients, an intraluminal agent require intensification during episodes of rejection, with asso- for eradication of cysts is recommended. ciated increased risk of infection.

usually last less than 2 weeks before spontaneously resolving Cyclospora lnfection in immunocompetent hosts. Immunocompromised patients, Cyclospora infections are typically acquired after consump- in particular patients with AIDS, can develop serious and pro tion of food or water that is fecally contaminated with longed infection. Diagnosis from stool can be pursued micro- Cyclospora oocysts. In the United States, many of these infec- scopically by visualization of oocysts with modified acid-fast tions have been traced to imported fresh produce from tropical staining, EIA or direct immunofluorescent antibody testing, or and subtropical areas or have occurred in travelers to endemic molecular testing. Treatment for immunocompetent patients areas. The incubation period is approximately 1 week. usually consists of supportive care. When antimicrobial agents Symptoms can last for several weeks and may be more pro are considered for severe or prolonged infection, nitazoxanide nounced in HlV-infected patients (Table 46). is recommended. In HlV-infected patients, antiretroviral ther- apy is most effective in resolving infection. I(EY POIl{T o Cyclosporo infection is typically diagnosed microscopi, I(EY POIilTS cally by visualization of oocysts with modified acid-fast o Municipal water supplies and swimming pools can be a staining, microscopy with ultraviolet fluorescence, or source of Crgptosporidium infection. molecular testing; trimethoprim-sulfamethoxazole is o Microscopic visualization of oocysts in stool using modi- recommended for treatment of symptomatic infection. fied acid-fast staining, erzyme immunoassay or direct immunofluorescent antibody testing, or molecular testing can provide a diagnosis of Cryptosporidiuminfection. o Treatmentof Cryptosporidium infection consists of I nfections in Transplant supportive care for most immunocompetent hosts or nitazoxanide for severe or prolonged infection; antiret- Recipients roviral therapy is most effective in resolving infection in lntroduction HlV-infected patients. The occurrence of solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) procedures Amebiasis continues to increase, as do long term survival rates owing to Entamoeba histolytico is responsible for amebiasis. In the improved management of rejection and decreased complica- United States, most infections are diagnosed in travelers return- tions. With more patients living longer after transplantation, ing from visits to unsanitary tropical or developing countries, awareness of principles involved in the recognition and pre- immigrants from these areas, persons in institutionalized set- vention of infection in transplant recipients remains impor- tings, or those who practice oral-anal sex. Amebiasis is highly tant for physicians who are not transplant specialists. infectious, with ingestion of only a small number of infective Despite improvements in immunosuppression and anti- cysts needed for infection. The incubation period is 2 to 4 weeks. microbial therapy, infection remains a significant cause of Clinical findings are described in Table 46. Colonic perforation, morbidity and mortality after SOT and HSCT. Infection is the peritonitis, and death may complicate more fulminant infec most common cause of death in the first year after SOT. tions. Risk factors for severe infection in adults include immu- Additionally, the interaction of the immune system and infec- nodeficiency. Microscopic visualization of cysts or trophozoites, tion is bidirectional; although immune suppression to prevent stool antigen immunoassay testing, stool molecular testing, and rejection increases risk of infection, infection also raises the serologic antibody testing can provide a diagnosis, although the risk of rejection. latter does not distinguish current from remote infection. Treatment is recommended for all infected patients. In sympto matic patients, treatment with metronidazole or tinidazole is Antirejection Drugs in recommended initially for parasitic clearance followed by an Transplant Recipients intraluminal amebicide, such as paromomycin or diloxanide, Success after transplantation depends on modulating the for cyst clearance. In asymptomatic infections, an intraluminal immune system to prevent organ rejection in SOT and to mini- agent for eradication of cysts is recommended. mize graft-versus-host disease (GVHD) in allogeneic HSCT. IEY POIl{I Antirejection regimens involve multiple agents (TaUte 5O)with o Treatment is recommended for all patients with amebi- different mechanisms of action, which are chosen to minimize overlapping toxicities. After SOI an induction and mainte- asis; for symptomatic patients, metronidazole or tinida- nance strate$/ is applied; immunosuppression is most inten- zole is recommended initially for parasitic clearance fol- sive in the first month after transplantation and often includes lowed by an intraluminal amebicide for cyst clearance, lymphocyte depletion therapy. Immunosuppression may and for asymptomatic patients, an intraluminal agent require intensification during episodes of rejection, with asso- for eradication of cysts is recommended. ciated increased risk of infection. 75

lnfections in Transplant Recipients TABLE 50" lmmunosuppressive Agents Used in TABLE 51 . Timeline of Common lnfections after Solid Transplantation Organ Transplantation Class Agents Early Period Middle Period Late Period (<1 Month after (1-6 Months after (>6 Months after Glucocorticoids Prednisone, others Transplantation)" Transplantation) Transplantation) Cytotoxic agents (DNA Mycophenolate mofetil Cytomegalovirus Epstein-Barr virus Staphylococcus synthesis inhibitors, infection (including PTLD) Mycophenolate sodium aureus infection antimetabolites) (including infection Azathioprine Epstein-Barr virus methicillin- (including PTLD) Va ricella-zoster Methotrexate resistant) infection virus infection Cyclophosphamide Nosocomialgram- Herpes simplex Community- negative bacterial Calcineurin pathway Cyclosporine virus infection acquired infection pneumonia inhibitors Va ricella-zoster Tacrolimus Clostridioides virus infection Urinary tract mTOR inhibitors Sirolimus (rapamycin) difficile colitis infections Polyomavirus BK Everolimus Candida infection infection Polyomavirus BK Lymphocyte-depleting Aspergillus infection Pneumocystis antibodies infection jiroveciiinfection Cytomegalovirus Polyclonal Antithymocyte g lobulins Surgicalsite infection Toxoplasma, infections Monoclonal Muromonab (anti-CD3) Trypanosoma, Hospital-acquired Strongyloides Basil iximab (anti-l L-2 receptor) pneumonia Listeria infection Daclizu ma b (a nti-l L-2 receptor) Catheter-related Nocardia infection Rituximab (anti-CD20) bacteremia Tuberculosis Alemtuzumab (anti-CD52 ) Urinary tract reactivation infections lL-2 = interleukin-2; mTOR = mammalian target of rapamycin Fungal infections, including Cryptococcus Steroid-sparing or minimizing regimens are increasingly PTLD = posttransplant lym phoproliferative disorder. used to avoid the toxicities of long-term steroid therapy. "For opportunistic infections in the Iate period, risk depends on level of Tacrolimus, cyclosporine, or sirolimus are the cornerstones, immunosuppression. lnfections such as Pneumocystis and other fungi, Listeria, and Nocardia can be seen in the late period in patients with higher immunosuppression. usually with mycophenolate or, less commonly, azathioprine. Drug interactions are common with these agents, and many drugs can affect antirejection medication levels. Monitoring is in the late period depends on the immunosuppression level important to balance adequate immunosuppression with required. In the first month after SOT, infections are similar to toxicity. those seen in other hospitalized postsurgical patients, includ- ing a risk of resistant bacteria, and most often involve the KEY POIl{T lungs, urinary tract, and surgical sites. The middle period usu- o Glucocorticoid-sparing or minimizing regimens (with ally encompasses the most intensive immunosuppression, tacrolimus, cyclosporine, or sirolimus) are increasingly with significant risk for viral (such as cytomegalovirus) and used to avoid the toxicities of long-term steroid therapy. fungal (such as Pneumocustis) infections owing to defects in cell-mediated immunity. If immunosuppression can be de- escalated during the late period, risk for oppotunistic infec- Posft ra nspla ntation I nfections tions decreases overall, but patients remain at risk for certain Timeline and Type of Transplant viral infections and have increased risk for community- Infection may occur at any time after transplantation, but acquired bacterial infections. periods of highest immunosuppression, usually within the For some infections, the risk strongly depends on donor first few months after transplantation , carry the highest likeli- and recipient characteristics. Standard donor and recipient hood. Risk for infection is also affected by pre-existing condi- pretransplantation testing includes serologies for cytomegalo- tions (such as diabetes mellitus, cirrhosis, or neutropenia) and virus; Epstein-Barr virus; varicella-zoster virus; HIV; hepatitis by colonization with resistant organisms (such as Burkholderia B, C, and E viruses; syphilis; toxoplasmosis; and Strongyloides, in cystic fibrosis). Leishmanio, and Trypanosomaif from an endemic or€s; ond The specific infection risk varies depending on the time interferon-y release assay for latent tuberculosis infection. after transplantation. Table 51 shows the typical timeline of Immunosuppressive drugs and changed anatomy after trans- risk for specific infections after SOT. However, the timeline plantation may also contribute to altered presentations, mak- restarts when treating episodes of rejection, and infection risk ing diagnosis of common infections more challenging.

TABLE 50" lmmunosuppressive Agents Used in TABLE 51 . Timeline of Common lnfections after Solid Transplantation Organ Transplantation Class Agents Early Period Middle Period Late Period (<1 Month after (1-6 Months after (>6 Months after Glucocorticoids Prednisone, others Transplantation)" Transplantation) Transplantation) Cytotoxic agents (DNA Mycophenolate mofetil Cytomegalovirus Epstein-Barr virus Staphylococcus synthesis inhibitors, infection (including PTLD) Mycophenolate sodium aureus infection antimetabolites) (including infection Azathioprine Epstein-Barr virus methicillin- (including PTLD) Va ricella-zoster Methotrexate resistant) infection virus infection Cyclophosphamide Nosocomialgram- Herpes simplex Community- negative bacterial Calcineurin pathway Cyclosporine virus infection acquired infection pneumonia inhibitors Va ricella-zoster Tacrolimus Clostridioides virus infection Urinary tract mTOR inhibitors Sirolimus (rapamycin) difficile colitis infections Polyomavirus BK Everolimus Candida infection infection Polyomavirus BK Lymphocyte-depleting Aspergillus infection Pneumocystis antibodies infection jiroveciiinfection Cytomegalovirus Polyclonal Antithymocyte g lobulins Surgicalsite infection Toxoplasma, infections Monoclonal Muromonab (anti-CD3) Trypanosoma, Hospital-acquired Strongyloides Basil iximab (anti-l L-2 receptor) pneumonia Listeria infection Daclizu ma b (a nti-l L-2 receptor) Catheter-related Nocardia infection Rituximab (anti-CD20) bacteremia Tuberculosis Alemtuzumab (anti-CD52 ) Urinary tract reactivation infections lL-2 = interleukin-2; mTOR = mammalian target of rapamycin Fungal infections, including Cryptococcus Steroid-sparing or minimizing regimens are increasingly PTLD = posttransplant lym phoproliferative disorder. used to avoid the toxicities of long-term steroid therapy. "For opportunistic infections in the Iate period, risk depends on level of Tacrolimus, cyclosporine, or sirolimus are the cornerstones, immunosuppression. lnfections such as Pneumocystis and other fungi, Listeria, and Nocardia can be seen in the late period in patients with higher immunosuppression. usually with mycophenolate or, less commonly, azathioprine. Drug interactions are common with these agents, and many drugs can affect antirejection medication levels. Monitoring is in the late period depends on the immunosuppression level important to balance adequate immunosuppression with required. In the first month after SOT, infections are similar to toxicity. those seen in other hospitalized postsurgical patients, includ- ing a risk of resistant bacteria, and most often involve the KEY POIl{T lungs, urinary tract, and surgical sites. The middle period usu- o Glucocorticoid-sparing or minimizing regimens (with ally encompasses the most intensive immunosuppression, tacrolimus, cyclosporine, or sirolimus) are increasingly with significant risk for viral (such as cytomegalovirus) and used to avoid the toxicities of long-term steroid therapy. fungal (such as Pneumocustis) infections owing to defects in cell-mediated immunity. If immunosuppression can be de- escalated during the late period, risk for oppotunistic infec- Posft ra nspla ntation I nfections tions decreases overall, but patients remain at risk for certain Timeline and Type of Transplant viral infections and have increased risk for community- Infection may occur at any time after transplantation, but acquired bacterial infections. periods of highest immunosuppression, usually within the For some infections, the risk strongly depends on donor first few months after transplantation , carry the highest likeli- and recipient characteristics. Standard donor and recipient hood. Risk for infection is also affected by pre-existing condi- pretransplantation testing includes serologies for cytomegalo- tions (such as diabetes mellitus, cirrhosis, or neutropenia) and virus; Epstein-Barr virus; varicella-zoster virus; HIV; hepatitis by colonization with resistant organisms (such as Burkholderia B, C, and E viruses; syphilis; toxoplasmosis; and Strongyloides, in cystic fibrosis). Leishmanio, and Trypanosomaif from an endemic or€s; ond The specific infection risk varies depending on the time interferon-y release assay for latent tuberculosis infection. after transplantation. Table 51 shows the typical timeline of Immunosuppressive drugs and changed anatomy after trans- risk for specific infections after SOT. However, the timeline plantation may also contribute to altered presentations, mak- restarts when treating episodes of rejection, and infection risk ing diagnosis of common infections more challenging. 76

lnfections in Transplant Recipients Noninfectious complications such as GVHD or malignancy shows the timeline of risk for specific infections after alloge- may also be confused with infection. neic HSCT. Risk after HSCT is much greater for allogeneic than autologous transplantation because of the myeloablative con- I( EY PO I TTS ditioning regimen. After allogeneic HSCI patients undergo a o Infection may occur at any time after transplantation prolonged period of intense neutropenia, putting them at risk but is most likely at periods of highest immunosuppres- for bacterial infections, Condido and mold infections, and sion; the risk for specific organisms varies depending herpes simplex and other virus reactivation. This is followed on the time after transplantation. by a prolonged period of impaired cell-mediated and humoral o Infection risk is much greater after allogeneic than immunity because of immunosuppression to reduce GVHD. autologous hematopoietic stem cell transplantation Development of chronic GVHD can also increase risk for because of myeloablative conditioning with a prolonged infections caused by immune system effects and breakdowns period of neutropenia and immunosuppression given to in mucosal and other barriers. Infections in this later period reduce graft-versus-host disease. are similar to those in the later period after SOT. Figure 33

Noninfectious complications such as GVHD or malignancy shows the timeline of risk for specific infections after alloge- may also be confused with infection. neic HSCT. Risk after HSCT is much greater for allogeneic than autologous transplantation because of the myeloablative con- I( EY PO I TTS ditioning regimen. After allogeneic HSCI patients undergo a o Infection may occur at any time after transplantation prolonged period of intense neutropenia, putting them at risk but is most likely at periods of highest immunosuppres- for bacterial infections, Condido and mold infections, and sion; the risk for specific organisms varies depending herpes simplex and other virus reactivation. This is followed on the time after transplantation. by a prolonged period of impaired cell-mediated and humoral o Infection risk is much greater after allogeneic than immunity because of immunosuppression to reduce GVHD. autologous hematopoietic stem cell transplantation Development of chronic GVHD can also increase risk for because of myeloablative conditioning with a prolonged infections caused by immune system effects and breakdowns period of neutropenia and immunosuppression given to in mucosal and other barriers. Infections in this later period reduce graft-versus-host disease. are similar to those in the later period after SOT. Figure 33 Phase l, Preen graft ment, Phase ll, Postengraftment, Phase lll, Late phase, <30 days 30-1 00 days >1 00 days

Noninfectious complications such as GVHD or malignancy shows the timeline of risk for specific infections after alloge- may also be confused with infection. neic HSCT. Risk after HSCT is much greater for allogeneic than autologous transplantation because of the myeloablative con- I( EY PO I TTS ditioning regimen. After allogeneic HSCI patients undergo a o Infection may occur at any time after transplantation prolonged period of intense neutropenia, putting them at risk but is most likely at periods of highest immunosuppres- for bacterial infections, Condido and mold infections, and sion; the risk for specific organisms varies depending herpes simplex and other virus reactivation. This is followed on the time after transplantation. by a prolonged period of impaired cell-mediated and humoral o Infection risk is much greater after allogeneic than immunity because of immunosuppression to reduce GVHD. autologous hematopoietic stem cell transplantation Development of chronic GVHD can also increase risk for because of myeloablative conditioning with a prolonged infections caused by immune system effects and breakdowns period of neutropenia and immunosuppression given to in mucosal and other barriers. Infections in this later period reduce graft-versus-host disease. are similar to those in the later period after SOT. Figure 33 Phase l, Preen graft ment, Phase ll, Postengraftment, Phase lll, Late phase, <30 days 30-1 00 days >1 00 days Neutropenia, mucositis, lmpaired cellular immunity lmpaired cellular and Host immune humoral immunity and and acute graft-versus- and acute and chronic graft- system defect chronic graft-versus- host disease versus-host disease host disease

Neutropenia, mucositis, lmpaired cellular immunity lmpaired cellular and Host immune humoral immunity and and acute graft-versus- and acute and chronic graft- system defect chronic graft-versus- host disease versus-host disease host disease Device risk Central line Allogeneic Respiratory and vrruses patients Herpes simplex virus",b Cytomegalovirus",b Varicella-zoster virusb Facultative gram-negative bacilli Epstein-Barr viru lym phoprol iferative d iseaseb +> Stre pto coccu s e p i d e rm i d i s Gastro i ntesti na I tract Streptococcus species - Encapsulated bacteria (e.9., pneumococcus) All Candida species ctes

Gastro i ntesti na I tract Streptococcus species - Encapsulated bacteria (e.9., pneumococcus) All Candida species ctes Toxoplasma gondii + \ / Stro n gyl oi d es stercora/is

Toxoplasma gondii + \ / Stro n gyl oi d es stercora/is 0 30 100 360 Days after transplant High incidence (>10%) Low incidence (<10%) +> Episodic and endemic +> Continuous risk +> F lG U R E 3 3. Phases of opportunistic infections in allogeneic hematopoietic stem cell transplant recipients. 'Without standard prophylaxis. bPrimarily among persons who are seropositive before transplantation. 77

lnfections in Transplant Recipients Specific Posttransplantation I nfections disease. Related to persistently low antibody levels, encapsu- Viral Infections lated organisms such as Streptococcus pneumoniae remain Cytomegalovirus is the most significant viral infection after common even late after HSCT. transplantation, with risk for infection depending on donor and recipient serology. After SOT, the risk for cytomegalovi- Fungal Infections rus is highest (>SOZ) for donor-positive/recipient negative, Fungal infections are most common in the middle period after intermediate (15'X,-20'2,) for recipient-positive, and lowest for SOT but may also occur late, especially in the setting of donor negative/recipient-negative transplantations. Risk is increased immunosuppression for the treatment of rejection also significantly increased with use of lymphocyte- or profound T-cell depression secondary to cytomegalovirus depleting agents. Comparatively, after allogeneic HSCI the infection. Without prophylaxis, the most common fungal risk of cytomegalovirus is highest for donor-negative/ infection is Pneumocystis pneumonia, which presents as a recipient positive transplantations. Cytomegalovirus is an more acute and severe pneumonitis in patients after trans immunomodulatory virus, and active cytomegalovirus infec- plantation than in those with AIDS. Cryptococcosis usually tion after transplantation is associated with increased rates of presents as subacute meningitis with fever, headache, mental rejection and GVHD, as well as increases in other opportun status changes, and lymphocytic pleocytosis in cerebrospinal istic infections and posttransplant lymphoproliferative disor- fluid, although skin and other organ involvement may also der (PTLD). Cytomegalovirus often presents as a nonspecific oCCUr; cryptococcal antigen testing is key to diagnosis. viral syndrome with fever and cytopenias. Specific organ Histoplasmosis may also occur in geographically endemic disease owing to cytomegalovirus includes pneumonitis areas and is more likely to present with disseminated disease (more common in HSCT than SOT), encephalitis, hepatitis, after transplantation. Mucocutaneous candidiasis is common and other gastrointestinal sites. Colitis is the most common early after SOT and HSCT. Invasive Candida infections and manifestation of cytomegalovirus gastrointestinal disease candidemia can be seen, especially in the neutropenic phase after SOT, whereas esophagitis is more common after HSCT. after HSCT, as can aspergillosis and other invasive molds, such Definitive diagnosis of organ disease depends on demonstra- as Mucor. The risk for invasive fungal infections after HSCT is tion of cytomegalovirus in biopsy, although presumptive also increased in later periods by the use of immunosuppres- diagnosis can be made based on cytomegalovirus viremia, sive agents for GVHD. In SOT, pulmonary aspergillosis is most using quantitative nucleic acid amplification testing, in the common after lung transplantation. appropriate clinical setting. Epstein-Barr virus is most significant for its relationship Protozoa and Helminths to PTLD resulting from B-cell proliferation; PTLD should be Toxoplasma gondii, a risk particularly for heart transplant suspected in any patient in the middle or late period present- recipients, is a protozoan that can reactivate with immuno- ing with lymphadenopathy or an extranodal mass, often with suppression, causing encephalitis with fever, headache, and fever. Treatment of PTLD involves rituximab and decreasing focal neurologic deficits with multiple ring-enhancing brain immunosuppression. Reactivation of herpes simplex virus is Iesions on imaging (see HIV/AIDS) . Strongyloides can cause a especially common after HSCT and can be reduced with acy- hyperinfection syndrome with significant immunosuppres- clovir prophylaxis (if the patient is not already receiving an sion (especially glucocorticoid use), often with secondary agent for cytomegalovirus). Patients with chronic hepatitis B pneumonia and gram-negative bacteremia. Reactivation of can have disease flares if not taking suppressive therapy (see Trypanosomeor Leishmanio can also occur after transplanta- MKSAP 19 Gastroenterologz & HepatoloSl). Polyomavirus BK tion, if the recipient or donor was from an endemic area. can cause nephropathy after kidney transplantation, increas r( EY P0 r 1{IS ing the risk of graft rejection, and hemorrhagic cystitis, par . C),tomegalovirus is the most significant viral infection ticularly in HSCT. after transplantation and may present as a nonspecific viral syndrome with fever and cytopenias orwith specific Bacterial Infections organ disease, including pneumonitis, encephalitis, Bacterial infections are common in the early period after SOT esophagitis, and colitis. and during neutropenia after HSCT. These are often typical . Clostridioides dfficile colitis is common after trans- nosocomial infections, including resistant organisms such as plantation, complicating the extensive antibiotic use methicillin resistant staphylococci, vancomycin-resistant that accompanies transplantation. enterococci, and multidrug-resistant gram negative organ- . MAcobacterium tuberculosis can reactivate with the isms. Clostridioides difftcile colitis is common, especially with immunosuppression of transplantation and may present the extensive antibiotic use that accompanies transplantation. with an atypical pattern on chest radiography or with My cobacterium tubercu losis can reactivate with the immuno- extrapulmonary disease. suppression of transplantation and may present with an affpi- (Continued) cal pattern on chest radiography or with extrapulmonary

Specific Posttransplantation I nfections disease. Related to persistently low antibody levels, encapsu- Viral Infections lated organisms such as Streptococcus pneumoniae remain Cytomegalovirus is the most significant viral infection after common even late after HSCT. transplantation, with risk for infection depending on donor and recipient serology. After SOT, the risk for cytomegalovi- Fungal Infections rus is highest (>SOZ) for donor-positive/recipient negative, Fungal infections are most common in the middle period after intermediate (15'X,-20'2,) for recipient-positive, and lowest for SOT but may also occur late, especially in the setting of donor negative/recipient-negative transplantations. Risk is increased immunosuppression for the treatment of rejection also significantly increased with use of lymphocyte- or profound T-cell depression secondary to cytomegalovirus depleting agents. Comparatively, after allogeneic HSCI the infection. Without prophylaxis, the most common fungal risk of cytomegalovirus is highest for donor-negative/ infection is Pneumocystis pneumonia, which presents as a recipient positive transplantations. Cytomegalovirus is an more acute and severe pneumonitis in patients after trans immunomodulatory virus, and active cytomegalovirus infec- plantation than in those with AIDS. Cryptococcosis usually tion after transplantation is associated with increased rates of presents as subacute meningitis with fever, headache, mental rejection and GVHD, as well as increases in other opportun status changes, and lymphocytic pleocytosis in cerebrospinal istic infections and posttransplant lymphoproliferative disor- fluid, although skin and other organ involvement may also der (PTLD). Cytomegalovirus often presents as a nonspecific oCCUr; cryptococcal antigen testing is key to diagnosis. viral syndrome with fever and cytopenias. Specific organ Histoplasmosis may also occur in geographically endemic disease owing to cytomegalovirus includes pneumonitis areas and is more likely to present with disseminated disease (more common in HSCT than SOT), encephalitis, hepatitis, after transplantation. Mucocutaneous candidiasis is common and other gastrointestinal sites. Colitis is the most common early after SOT and HSCT. Invasive Candida infections and manifestation of cytomegalovirus gastrointestinal disease candidemia can be seen, especially in the neutropenic phase after SOT, whereas esophagitis is more common after HSCT. after HSCT, as can aspergillosis and other invasive molds, such Definitive diagnosis of organ disease depends on demonstra- as Mucor. The risk for invasive fungal infections after HSCT is tion of cytomegalovirus in biopsy, although presumptive also increased in later periods by the use of immunosuppres- diagnosis can be made based on cytomegalovirus viremia, sive agents for GVHD. In SOT, pulmonary aspergillosis is most using quantitative nucleic acid amplification testing, in the common after lung transplantation. appropriate clinical setting. Epstein-Barr virus is most significant for its relationship Protozoa and Helminths to PTLD resulting from B-cell proliferation; PTLD should be Toxoplasma gondii, a risk particularly for heart transplant suspected in any patient in the middle or late period present- recipients, is a protozoan that can reactivate with immuno- ing with lymphadenopathy or an extranodal mass, often with suppression, causing encephalitis with fever, headache, and fever. Treatment of PTLD involves rituximab and decreasing focal neurologic deficits with multiple ring-enhancing brain immunosuppression. Reactivation of herpes simplex virus is Iesions on imaging (see HIV/AIDS) . Strongyloides can cause a especially common after HSCT and can be reduced with acy- hyperinfection syndrome with significant immunosuppres- clovir prophylaxis (if the patient is not already receiving an sion (especially glucocorticoid use), often with secondary agent for cytomegalovirus). Patients with chronic hepatitis B pneumonia and gram-negative bacteremia. Reactivation of can have disease flares if not taking suppressive therapy (see Trypanosomeor Leishmanio can also occur after transplanta- MKSAP 19 Gastroenterologz & HepatoloSl). Polyomavirus BK tion, if the recipient or donor was from an endemic area. can cause nephropathy after kidney transplantation, increas r( EY P0 r 1{IS ing the risk of graft rejection, and hemorrhagic cystitis, par . C),tomegalovirus is the most significant viral infection ticularly in HSCT. after transplantation and may present as a nonspecific viral syndrome with fever and cytopenias orwith specific Bacterial Infections organ disease, including pneumonitis, encephalitis, Bacterial infections are common in the early period after SOT esophagitis, and colitis. and during neutropenia after HSCT. These are often typical . Clostridioides dfficile colitis is common after trans- nosocomial infections, including resistant organisms such as plantation, complicating the extensive antibiotic use methicillin resistant staphylococci, vancomycin-resistant that accompanies transplantation. enterococci, and multidrug-resistant gram negative organ- . MAcobacterium tuberculosis can reactivate with the isms. Clostridioides difftcile colitis is common, especially with immunosuppression of transplantation and may present the extensive antibiotic use that accompanies transplantation. with an atypical pattern on chest radiography or with My cobacterium tubercu losis can reactivate with the immuno- extrapulmonary disease. suppression of transplantation and may present with an affpi- (Continued) cal pattern on chest radiography or with extrapulmonary 78

lnfections in Transplant Recipients l(EY P0ltllt {onfiaucd} in Table 52. Most immunizations are safe in patients after o Without prophylaxis, the most common fungal infec transplantation except for live virus vaccines, which should be tion is Pneumocysfis pneumonia, which presents as a avoided after transplantation. more acute and severe pneumonitis in patients after Trimethoprim-sulfamethoxazole is one of the most transplantation than in those with AIDS. important prophylactic medications after transplantation. Used to prevent Pneumocystis, it may also reduce toxoplas- mosis and certain bacteria, including Listeriaand agents caus- Prevention of Infections in ing urinary tract infections. Antifungal prophylaxis is indicated during the early Transplant Recipients months after HSCT and may need to be extended in the setting Prevention is preferred over treatment strategies for most of GVHD. Coverage should include Candida and Aspergillus, common infections after transplantation because most oppor- typically with posaconazole or voriconazole. tunistic infections have devastating effects and the cost and Strategies to reduce the effects of cytomegalovirus toxicity of prophylaxis and immunization are relatively low. include primary prophylaxis, usually with valganciclovir, or Recommended immunizations for SOT and HSCT are shown regular monitoring for active cytomegalovirus replication by

l(EY P0ltllt {onfiaucd} in Table 52. Most immunizations are safe in patients after o Without prophylaxis, the most common fungal infec transplantation except for live virus vaccines, which should be tion is Pneumocysfis pneumonia, which presents as a avoided after transplantation. more acute and severe pneumonitis in patients after Trimethoprim-sulfamethoxazole is one of the most transplantation than in those with AIDS. important prophylactic medications after transplantation. Used to prevent Pneumocystis, it may also reduce toxoplas- mosis and certain bacteria, including Listeriaand agents caus- Prevention of Infections in ing urinary tract infections. Antifungal prophylaxis is indicated during the early Transplant Recipients months after HSCT and may need to be extended in the setting Prevention is preferred over treatment strategies for most of GVHD. Coverage should include Candida and Aspergillus, common infections after transplantation because most oppor- typically with posaconazole or voriconazole. tunistic infections have devastating effects and the cost and Strategies to reduce the effects of cytomegalovirus toxicity of prophylaxis and immunization are relatively low. include primary prophylaxis, usually with valganciclovir, or Recommended immunizations for SOT and HSCT are shown regular monitoring for active cytomegalovirus replication by TABLE 52. lmmunization Recommendations for Adult Recipients of Transplantsu lmmunization Recommendations for Solid Organ Recommendations for Hematopoietic Stem Transplantation Cell Transplantationb Pneumococcal Before transplantation: PCV13 followed 8 weeks 3-6 months after transplantation: three doses of later by PPSV23 PCV13 After transpla ntation : PCV1 3 (if not admin istered 1 2 months after transplantation: one dose of pretransplantation) 2-6 months after PPSV23 transplantation; one dose PPSV23 at least 8 weeks after PCV13 and 5 years after any previous PPSV23 lnfluenza (inactivated only) Annually Annually Tdap Before tra nsplantation : complete series, 6 months after transplantation: three doses Tdap including Tdap booster MMR Contra i nd icated after transpla ntation 24 months after transplantation: one to two doses, only if no GVHD or immune suppression lnactivated polio Before transpla ntation : complete series 6-12 months after transplantation: three doses Haemophilus influenzae type B No recommendation 6-12 months after transplantation: three doses Meningococcal Per recom me ndations for nontra nspla nt patie nts 6 months after transplantation: both quadrivalent conjugate vaccine and serogroup B vaccine Hepatitis B Before transplantation: complete series if not 6-12 months after transplantation: three doses if already immune indications for nontransplant patients are met Hepatitis A Before transplantation: complete series if not Per recom mendati o ns for nontra nspla nt pati e nts already immune Varicel la-zoster vi rus

TABLE 52. lmmunization Recommendations for Adult Recipients of Transplantsu lmmunization Recommendations for Solid Organ Recommendations for Hematopoietic Stem Transplantation Cell Transplantationb Pneumococcal Before transplantation: PCV13 followed 8 weeks 3-6 months after transplantation: three doses of later by PPSV23 PCV13 After transpla ntation : PCV1 3 (if not admin istered 1 2 months after transplantation: one dose of pretransplantation) 2-6 months after PPSV23 transplantation; one dose PPSV23 at least 8 weeks after PCV13 and 5 years after any previous PPSV23 lnfluenza (inactivated only) Annually Annually Tdap Before tra nsplantation : complete series, 6 months after transplantation: three doses Tdap including Tdap booster MMR Contra i nd icated after transpla ntation 24 months after transplantation: one to two doses, only if no GVHD or immune suppression lnactivated polio Before transpla ntation : complete series 6-12 months after transplantation: three doses Haemophilus influenzae type B No recommendation 6-12 months after transplantation: three doses Meningococcal Per recom me ndations for nontra nspla nt patie nts 6 months after transplantation: both quadrivalent conjugate vaccine and serogroup B vaccine Hepatitis B Before transplantation: complete series if not 6-12 months after transplantation: three doses if already immune indications for nontransplant patients are met Hepatitis A Before transplantation: complete series if not Per recom mendati o ns for nontra nspla nt pati e nts already immune Varicel la-zoster vi rus Live attenuated vaccine >4 weeks before transplantation: varicella if not >4 weeks before transplantation: varicella if not immune immune >4 weeks before transplantation: zoster if same 24 months after transplantation: two doses indications as nontransplant patients are met varicella if seronegative and only if no GVHD or immunosuppression Both contraindicated after transplantation Recom bi na nt adj uva nted Theoretically safe, but data in severely Theoretically safe, but data in severely zoster vaccrne i m m u nocom prom ised patients not yet avai lable; immunocompromised patients not yet available no recommendations after transplantation except for autologous HSCT; no recom mendations after tra nspla ntation Should be given before transplantation if possible Should be given before transplantation if possible Human papillomavirus Before tra nsplantation : per recom mendations Pe r recom mendations for no ntra nsp la nt pati e nts for nontransplant patients GVHD = graft-versus-host disease; MMR = measles, mumps, and rubella vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine; Tdap = 1s13nr., diphtheria, and acellular pertussis vaccine.

Live attenuated vaccine >4 weeks before transplantation: varicella if not >4 weeks before transplantation: varicella if not immune immune >4 weeks before transplantation: zoster if same 24 months after transplantation: two doses indications as nontransplant patients are met varicella if seronegative and only if no GVHD or immunosuppression Both contraindicated after transplantation Recom bi na nt adj uva nted Theoretically safe, but data in severely Theoretically safe, but data in severely zoster vaccrne i m m u nocom prom ised patients not yet avai lable; immunocompromised patients not yet available no recommendations after transplantation except for autologous HSCT; no recom mendations after tra nspla ntation Should be given before transplantation if possible Should be given before transplantation if possible Human papillomavirus Before tra nsplantation : per recom mendations Pe r recom mendations for no ntra nsp la nt pati e nts for nontransplant patients GVHD = graft-versus-host disease; MMR = measles, mumps, and rubella vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine; Tdap = 1s13nr., diphtheria, and acellular pertussis vaccine. "See MKSAP 19 General lnternal Medicine 2 for more information on vaccination recommendations and schedules. bFor multiple-dose immunizations, the time period between doses is generally 1-2 months 79

Health Care-Associated lnfections quantitative nucleic acid amplification testing and institution Prevention of pre-emptive therapy based on results. Monitoring and pre- Hand hygiene is the foundation of infection prevention, but less emptive therapy is more often used after HSCI partially than 50'2, adherence has been reported. Most facilities have because of increased concerns for neutropenia as an adverse improved in the last decade, with sustained improvement up to effect of prophylaxis and because prophylaxis was not found 90% adherence at some facilities. Hand hygiene should be per- to be superior to pre-emptive therapy in a randomized con formed at least before and after every patient contact. The World trolled trial. Letermovir, a novel antiviral agent without the Health Organization s five key hand hygiene moments (https'l hematologic toxicities of valganciclovir, is approved for prophy- wryvw.who. int /grsc /tools / SmomentsHandHygiene -A3. pdI?ua=l) laxis of cytomegalovirus infection in bone marrow transplant are commonly used to define hand hygiene opportunities. Hand recipients. For SOT, prophylaxis with valganciclovir is pre- hygiene should include all surfaces of the hands up to the ferred for patients at high risk (donor-positive/recipient- wrists, between fingers, and the fingertips (htfps://youtu.be/ negative, those receiving lymphocyte-depleting agents, lung IisgnbMfKvl). Alcohol-based hand rubs are generally preferred transplants) and is usually given for at least 3 to 6 months; to soap and water hand disinfection, except when hands are Ietermovir prophylaxis is under study in SOT recipients. visibly soiled, when personnel come in direct contact with t(EY P0lltTS blood or body fluids, or after contact with a patient with C. dtf HVC . Prophylaxis and immunization are preferred over treat- ficile infection or his or her environment. ing active infections after transplantation; live virus Standard precautions should be practiced for every patient vaccines should not be given after transplantation. to protect health care personnel from exposure to bloodborne o Monitoring by quantitative nucleic acid amplification pathogens. Blood and all body fluids except sweat are potentially

quantitative nucleic acid amplification testing and institution Prevention of pre-emptive therapy based on results. Monitoring and pre- Hand hygiene is the foundation of infection prevention, but less emptive therapy is more often used after HSCI partially than 50'2, adherence has been reported. Most facilities have because of increased concerns for neutropenia as an adverse improved in the last decade, with sustained improvement up to effect of prophylaxis and because prophylaxis was not found 90% adherence at some facilities. Hand hygiene should be per- to be superior to pre-emptive therapy in a randomized con formed at least before and after every patient contact. The World trolled trial. Letermovir, a novel antiviral agent without the Health Organization s five key hand hygiene moments (https'l hematologic toxicities of valganciclovir, is approved for prophy- wryvw.who. int /grsc /tools / SmomentsHandHygiene -A3. pdI?ua=l) laxis of cytomegalovirus infection in bone marrow transplant are commonly used to define hand hygiene opportunities. Hand recipients. For SOT, prophylaxis with valganciclovir is pre- hygiene should include all surfaces of the hands up to the ferred for patients at high risk (donor-positive/recipient- wrists, between fingers, and the fingertips (htfps://youtu.be/ negative, those receiving lymphocyte-depleting agents, lung IisgnbMfKvl). Alcohol-based hand rubs are generally preferred transplants) and is usually given for at least 3 to 6 months; to soap and water hand disinfection, except when hands are Ietermovir prophylaxis is under study in SOT recipients. visibly soiled, when personnel come in direct contact with t(EY P0lltTS blood or body fluids, or after contact with a patient with C. dtf HVC . Prophylaxis and immunization are preferred over treat- ficile infection or his or her environment. ing active infections after transplantation; live virus Standard precautions should be practiced for every patient vaccines should not be given after transplantation. to protect health care personnel from exposure to bloodborne o Monitoring by quantitative nucleic acid amplification pathogens. Blood and all body fluids except sweat are potentially testing for active cytomegalovirus replication and insti- infectious, regardless of the patient's presumed or known infec- tution of pre-emptive therapy based on results is pre- tion status. Personal protective equipment (gloves, gown, mask, ferred to ganciclovir primary prophylaxis of cytomega- and eye protection) are barriers protecting health care personnel

testing for active cytomegalovirus replication and insti- infectious, regardless of the patient's presumed or known infec- tution of pre-emptive therapy based on results is pre- tion status. Personal protective equipment (gloves, gown, mask, ferred to ganciclovir primary prophylaxis of cytomega- and eye protection) are barriers protecting health care personnel lovirus infection after hematopoietic stem cell from exposure to blood and body fluids. Protective equipment transplantation. should be donned and doffed carefully (https:/iwrmar.cdc.gov/ HAlipdfs /ppe /ppeposterla8.pdfl and followed by hand hygiene. Transmission-based precautions (airborne, contact, droplet) are performed in addition to standard precautions to prevent trans- Health Ca re-Associated mission of epidemiologically significant organisms (Table 53). lnfections Additional preventive measures include careful and judi cious device use, safe injection practices (one needle, one Epidemiology syringe, only one time), aseptic technique for invasive proce- Health care-associated infections (HCAI) have been linked dures and surgery and a clean environment and patient equip- to indwelling medical devices, prosthetic devices and ment. HCAI prevention "bundles" comprise three to five materials, surgery, invasive procedures, transmission of evidence-based processes of care that, when performed organisms between patients and health care personnel, together, consistently have a greater impact on decreasing and environmental factors. Approximately 3.2% of hospi- HCAIs than individual components performed inconsistently. talized patients acquire at least one HCAI, costing the U.S. All U.S. health care facilities are required to have an infec- health care system an estimated $28 billion to $45 billion tion prevention program. The infection prevention team is annually. HCAIs include pneumonia (ZS.S%), gastrointes- responsible for providing the knowledge and recommending tinal infections (Zt.gU), surgical site infections (16.2%), the means to minimize risks of acquiring an HCAI. bloodstream infections (12.2'/o; 73% associated with central IEY PO I1{T venous catheters), and urinary tract infections (UTIs, 9.1%; . Hand hygiene is the foundation of infection prevention; HVC 61.5% associated with catheters) . Clostridioides difficile is the World Health Organization has identified five key another common HCAI (see Gastrointestinal Syndromes); hand hygiene moments (before touching a patient, the incidence has begun declining after unprecedented before clean or aseptic procedure, after body fluid expo- high rates, although community-acquired C. difficile con sure risk, after touching a patient, and after touching tinues to rise. patient surroundings). Elimination of HCAIs remains important for the U.S. health care system. Thirty-five percent to 5S'2, of HCAIs are considered preventable. Progress toward elimination varies by type of infection. Central line-associated bloodstream infec- Catheter-Associated U ri na ry tions decreased by 19"/, and C. dfficile infections by 2O'/. Trast lnfestions between 2015 and 2017; catheter-associated UTIs decreased by Seventeen percent to 69% ofcatheter-associated urinary tract 5'lo between 2016 and 2Ol7 . infections (CAUTIs) may be preventable. Urinary catheters are

lovirus infection after hematopoietic stem cell from exposure to blood and body fluids. Protective equipment transplantation. should be donned and doffed carefully (https:/iwrmar.cdc.gov/ HAlipdfs /ppe /ppeposterla8.pdfl and followed by hand hygiene. Transmission-based precautions (airborne, contact, droplet) are performed in addition to standard precautions to prevent trans- Health Ca re-Associated mission of epidemiologically significant organisms (Table 53). lnfections Additional preventive measures include careful and judi cious device use, safe injection practices (one needle, one Epidemiology syringe, only one time), aseptic technique for invasive proce- Health care-associated infections (HCAI) have been linked dures and surgery and a clean environment and patient equip- to indwelling medical devices, prosthetic devices and ment. HCAI prevention "bundles" comprise three to five materials, surgery, invasive procedures, transmission of evidence-based processes of care that, when performed organisms between patients and health care personnel, together, consistently have a greater impact on decreasing and environmental factors. Approximately 3.2% of hospi- HCAIs than individual components performed inconsistently. talized patients acquire at least one HCAI, costing the U.S. All U.S. health care facilities are required to have an infec- health care system an estimated $28 billion to $45 billion tion prevention program. The infection prevention team is annually. HCAIs include pneumonia (ZS.S%), gastrointes- responsible for providing the knowledge and recommending tinal infections (Zt.gU), surgical site infections (16.2%), the means to minimize risks of acquiring an HCAI. bloodstream infections (12.2'/o; 73% associated with central IEY PO I1{T venous catheters), and urinary tract infections (UTIs, 9.1%; . Hand hygiene is the foundation of infection prevention; HVC 61.5% associated with catheters) . Clostridioides difficile is the World Health Organization has identified five key another common HCAI (see Gastrointestinal Syndromes); hand hygiene moments (before touching a patient, the incidence has begun declining after unprecedented before clean or aseptic procedure, after body fluid expo- high rates, although community-acquired C. difficile con sure risk, after touching a patient, and after touching tinues to rise. patient surroundings). Elimination of HCAIs remains important for the U.S. health care system. Thirty-five percent to 5S'2, of HCAIs are considered preventable. Progress toward elimination varies by type of infection. Central line-associated bloodstream infec- Catheter-Associated U ri na ry tions decreased by 19"/, and C. dfficile infections by 2O'/. Trast lnfestions between 2015 and 2017; catheter-associated UTIs decreased by Seventeen percent to 69% ofcatheter-associated urinary tract 5'lo between 2016 and 2Ol7 . infections (CAUTIs) may be preventable. Urinary catheters are 80

Hea lth Care-Associated I nfections TABL= 53. Transmission-Based Precautionsu Precaution Type lndications Precaution Examples Airborne Organisms transmitted from Airborne infection isolation room Chickenpox (pl us contact respiratory tract by small droplet (negative-pressure room); HCP precautions), tuberculosis, measles, nuclei (<5 microns) that travel long wear fit-tested N95 respirator SARS-CoV-2 distances on air currents (Figure 34) Contact Organisms transmitted by direct or Single room; gloves and gown for M ultidrug-resistant organisms (such indirect contact HCP entering room as MRSA, VRE, ESBL-producing g ram-negative organisms, CRE), Cl ostri d i oi d e s d iffi ci I e, rotavi rus Droplet Organisms transmitted from Single room; HCP wear face or I nfl ue nza, Bord ete I I a pefussis, respiratory tract by large dro p let surgical mask when within 3 feet of Nersseria meningitidis for first nuclei (>5 microns) that trave I less patient 24 hours of therapy, mumps than 3 feet on air currents CRE = carbapenem-resistant Enterobacteriaceae; ESBL = extended-spectrum p-lactamase; HCP = health care personnel; MRSA = methicillin-resistant Staphylococcus aureus; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; VRE = vancomycin-resistant enterococci. SARS-CoV-2 : airborne and contact).

respiratory tract by large dro p let surgical mask when within 3 feet of Nersseria meningitidis for first nuclei (>5 microns) that trave I less patient 24 hours of therapy, mumps than 3 feet on air currents CRE = carbapenem-resistant Enterobacteriaceae; ESBL = extended-spectrum p-lactamase; HCP = health care personnel; MRSA = methicillin-resistant Staphylococcus aureus; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; VRE = vancomycin-resistant enterococci. SARS-CoV-2 : airborne and contact). used in 15% to 25% of hospitalized patients in the United the risk of CAUTI. Nonadherence to aseptic technique (for States, compelling efforts to establish appropriateness criteria example, opening a closed system) and insertion by a less for catheter use. Adverse outcomes related to CAUTI include experienced operator also increase the risk. Patient-related pyelonephritis, perinephric abscess, and bacteremia (<SZ). risk factors include female sex, age older than 50 years, diabe- Escherichia coli is the most common CAUTI pathogen, tes mellitus, severe or nonsurgical underlying illness, and followed by Klebsiello pneumoniae/Klebsiella oxAtoca, serum creatinine level greater than 2.0 mg/dl (fi1.e pmol/L). Pseudomonos aeruginosa, and Enterococcus species ; antibi- Appropriate indications for indwelling urinary catheters are otic resistance among these pathogens is increasing. listed in Table 54. Management of urinary incontinence using Colonization with bacteria or yeast occurs within 48 external catheters is preferred when feasible. Provision of care hours of catheterization. Duration of catheterization is the in the ICU is not itself an indication for a catheter. primary modifiable risk factor for CAUTI; €ach day increases Diagnosis Patients with an indwelling urethral or suprapubic catheter (or catheter removed in the 48 hours before symptom onset) or using intermittent catheterization who have signs and symp- toms compatible with UTI (see Urinary Tract Infections for information), no other identifiable infection source, and 103 colony-forming units/ml or more of one or more bacterial species in a urine specimen are diagnosed with a CAUTI. Catheter-associated asymptomatic bacteriuria (>t03 colony- forming unitsiml without urinary tract signs or symptoms) is common and generally does not require treatment.

used in 15% to 25% of hospitalized patients in the United the risk of CAUTI. Nonadherence to aseptic technique (for States, compelling efforts to establish appropriateness criteria example, opening a closed system) and insertion by a less for catheter use. Adverse outcomes related to CAUTI include experienced operator also increase the risk. Patient-related pyelonephritis, perinephric abscess, and bacteremia (<SZ). risk factors include female sex, age older than 50 years, diabe- Escherichia coli is the most common CAUTI pathogen, tes mellitus, severe or nonsurgical underlying illness, and followed by Klebsiello pneumoniae/Klebsiella oxAtoca, serum creatinine level greater than 2.0 mg/dl (fi1.e pmol/L). Pseudomonos aeruginosa, and Enterococcus species ; antibi- Appropriate indications for indwelling urinary catheters are otic resistance among these pathogens is increasing. listed in Table 54. Management of urinary incontinence using Colonization with bacteria or yeast occurs within 48 external catheters is preferred when feasible. Provision of care hours of catheterization. Duration of catheterization is the in the ICU is not itself an indication for a catheter. primary modifiable risk factor for CAUTI; €ach day increases Diagnosis Patients with an indwelling urethral or suprapubic catheter (or catheter removed in the 48 hours before symptom onset) or using intermittent catheterization who have signs and symp- toms compatible with UTI (see Urinary Tract Infections for information), no other identifiable infection source, and 103 colony-forming units/ml or more of one or more bacterial species in a urine specimen are diagnosed with a CAUTI. Catheter-associated asymptomatic bacteriuria (>t03 colony- forming unitsiml without urinary tract signs or symptoms) is common and generally does not require treatment. Treatment Before initiating antimicrobial treatment, a urinalysis and urine culture should be obtained to determine if antimicrobial resistance is present and to guide definitive therapy. CAUTI management includes removing the urinary catheter (and only replacing if still needed). Removal is strongly recommended for catheters in place for 2 or more weeks because biofilm on the catheter makes it difficult to eradicate bacteriuria or funguria and may lead to antimicrobial resistance, Therapy should always be adjusted to the narrowest coverage spectmm possible based on culture results. Treatment is given for 5 to 7 days if symptoms resolve promptly and longer (to-14 days) for patients t I G U R E 3 4. Differences are shown between N95 respirators and medical masks. The N95 respirator (top)seals around the face and requires user fit testing. The medical with delayed response. Candiduria in a patient with a catheter mask (bottom) is also called a surgical or procedure mask. frequently represents colonization and rarely requires

Treatment Before initiating antimicrobial treatment, a urinalysis and urine culture should be obtained to determine if antimicrobial resistance is present and to guide definitive therapy. CAUTI management includes removing the urinary catheter (and only replacing if still needed). Removal is strongly recommended for catheters in place for 2 or more weeks because biofilm on the catheter makes it difficult to eradicate bacteriuria or funguria and may lead to antimicrobial resistance, Therapy should always be adjusted to the narrowest coverage spectmm possible based on culture results. Treatment is given for 5 to 7 days if symptoms resolve promptly and longer (to-14 days) for patients t I G U R E 3 4. Differences are shown between N95 respirators and medical masks. The N95 respirator (top)seals around the face and requires user fit testing. The medical with delayed response. Candiduria in a patient with a catheter mask (bottom) is also called a surgical or procedure mask. frequently represents colonization and rarely requires 81

Health Care-Associated lnfections TABLE 54. Appropriate lndications for Use of lndwelling TABLE 55. Prevention of Catheter-Associated Urinary Urinary Catheters Tract lnfection Indication Period Preventive Measures Management of acute urinary retention without bladder outlet Before Avoid catheterization whenever possible obstruction catheterization lnsert catheter only for appropriate Management of acute urinary retention with bladder outlet indications obstruction not related to infection or trauma Consider alternatives, such as condom Management of chronic urinary retention with bladder outlet catheters and i ntermittent catheterization obstruction when ISC is not feasible Ensure that only properly trained persons Attime of Management of stage lll or lV or unstageable pressure ulcers catheter insertion insert and maintain catheters that cannot be kept clear of urinary incontinence despite other Adhere to hand hygiene practices and urinary management strategies (e.g., barrier creams, absorbent standard (or appropriate isolation) pads, prom pted toi leti n g, non-i ndwel li n g catheters) precautions according to CDC HICPAC/ Hourly measurement of urine volume required to provide WHO guidelines treatment Use proper aseptic techniques and sterile Daily measurement of urine volume required to provide equipment when inserting the catheter treatment when it cannot be assessed by other volume (e.9., daily (acute care setting) weighing, physical examination)and urine collection (e.9., urinal, After catheter Promote early catheter removal whenever bedside commode, bedpan, external catheter, ISC) strategies rnsertron possible Collection of a single 24-hour urine sample needed for Secure the catheter diagnostic test that cannot be obtained by other urine collection strategies Use aseptic technique when handling the catheter, including for sample collection Reduction in instances of acute, severe pain with movement from the designated port (not collecting when other urine management strategies are difficult bug) lmprovement in comfort when urine collection by catheter Maintain a closed drainage system addresses patient and family goals in a dying patient Avoid unnecessary system Management of gross hematuria with blood clots in urine disconnections Management of clinical condition for which ISC or external Maintain unobstructed urine flow catheter is appropriate but placement is difficult or bladder emptying is inadequate for the patient with non-indwelling Keep the collecting bag below the level strategies of the bladder and off the floor

TABLE 54. Appropriate lndications for Use of lndwelling TABLE 55. Prevention of Catheter-Associated Urinary Urinary Catheters Tract lnfection Indication Period Preventive Measures Management of acute urinary retention without bladder outlet Before Avoid catheterization whenever possible obstruction catheterization lnsert catheter only for appropriate Management of acute urinary retention with bladder outlet indications obstruction not related to infection or trauma Consider alternatives, such as condom Management of chronic urinary retention with bladder outlet catheters and i ntermittent catheterization obstruction when ISC is not feasible Ensure that only properly trained persons Attime of Management of stage lll or lV or unstageable pressure ulcers catheter insertion insert and maintain catheters that cannot be kept clear of urinary incontinence despite other Adhere to hand hygiene practices and urinary management strategies (e.g., barrier creams, absorbent standard (or appropriate isolation) pads, prom pted toi leti n g, non-i ndwel li n g catheters) precautions according to CDC HICPAC/ Hourly measurement of urine volume required to provide WHO guidelines treatment Use proper aseptic techniques and sterile Daily measurement of urine volume required to provide equipment when inserting the catheter treatment when it cannot be assessed by other volume (e.9., daily (acute care setting) weighing, physical examination)and urine collection (e.9., urinal, After catheter Promote early catheter removal whenever bedside commode, bedpan, external catheter, ISC) strategies rnsertron possible Collection of a single 24-hour urine sample needed for Secure the catheter diagnostic test that cannot be obtained by other urine collection strategies Use aseptic technique when handling the catheter, including for sample collection Reduction in instances of acute, severe pain with movement from the designated port (not collecting when other urine management strategies are difficult bug) lmprovement in comfort when urine collection by catheter Maintain a closed drainage system addresses patient and family goals in a dying patient Avoid unnecessary system Management of gross hematuria with blood clots in urine disconnections Management of clinical condition for which ISC or external Maintain unobstructed urine flow catheter is appropriate but placement is difficult or bladder emptying is inadequate for the patient with non-indwelling Keep the collecting bag below the level strategies of the bladder and off the floor = intermittent straight catheterization Empty the collecting bag regularly, using a separate collecting container for each patient treatment. Candidq CAUTI is considered when signifi cant can- CDC = Centers for Disease Control and Prevention; HICPAC = Healthcare lnfection diduria persists despite catheter removal or replacement and Control Practices Advisory Committee; WHO = World Health Organization.

= intermittent straight catheterization Empty the collecting bag regularly, using a separate collecting container for each patient treatment. Candidq CAUTI is considered when signifi cant can- CDC = Centers for Disease Control and Prevention; HICPAC = Healthcare lnfection diduria persists despite catheter removal or replacement and Control Practices Advisory Committee; WHO = World Health Organization. the patient is symptomatic. CAUTIs caused by Candido species requiring treatment should be treated for 14 days. l( EY P0lt{TS (cominued) o Candiduria in a patient with a catheter frequently rep HVC Prevention resents colonization and rarely requires treatment. Key prevention strategies include appropriately limiting uri- nary catheter use (see Table 54) and considering other options o Antimicrobial- or antiseptic-coated catheters have not HVC

the patient is symptomatic. CAUTIs caused by Candido species requiring treatment should be treated for 14 days. l( EY P0lt{TS (cominued) o Candiduria in a patient with a catheter frequently rep HVC Prevention resents colonization and rarely requires treatment. Key prevention strategies include appropriately limiting uri- nary catheter use (see Table 54) and considering other options o Antimicrobial- or antiseptic-coated catheters have not HVC associated with lower infection risk (intermittent straight shown benefit for short-term or long-term catheteriza- catheterization, external catheters) when urine collection is tion, are more expensive, and, in some cases, cause necessary (table 55). Most studies have not shown definitive more discomfort for patients. benefit of antimicrobial- or antiseptic-coated catheters for short- (<t+ days) or long-term catheterization; these catheters are more expensive and, in some cases (such as nitrofurazone- Surgical Site I nfeqtions coated catheters), cause more patient discomfort. Surgical site infections (SSIs) account for 23'/. of HCAIs. The over- r(EY POtt{TS all risk of developing an SSI is 1.9%. Wound class affects the risk of infection, with clean wounds having less than a 2% risk of HVC o Catheter-associated asymptomatic bacteriuria is common infection, clean contaminated wounds having less than a 10% and generally does not require treatment. risk, and contaminated wounds having a 20% risk. Most infec HVC . Catheter-associated urinary tract infection management tions occur within 30 days after surgery or within 90 days after includes catheter removal, with replacement only if still surgery with implants; however, infections can manifest beyond necessary' these ranges. Risk factors include patient-related, procedure- (continued) related, and postoperative factors (fante 56). The patient's skin

associated with lower infection risk (intermittent straight shown benefit for short-term or long-term catheteriza- catheterization, external catheters) when urine collection is tion, are more expensive, and, in some cases, cause necessary (table 55). Most studies have not shown definitive more discomfort for patients. benefit of antimicrobial- or antiseptic-coated catheters for short- (<t+ days) or long-term catheterization; these catheters are more expensive and, in some cases (such as nitrofurazone- Surgical Site I nfeqtions coated catheters), cause more patient discomfort. Surgical site infections (SSIs) account for 23'/. of HCAIs. The over- r(EY POtt{TS all risk of developing an SSI is 1.9%. Wound class affects the risk of infection, with clean wounds having less than a 2% risk of HVC o Catheter-associated asymptomatic bacteriuria is common infection, clean contaminated wounds having less than a 10% and generally does not require treatment. risk, and contaminated wounds having a 20% risk. Most infec HVC . Catheter-associated urinary tract infection management tions occur within 30 days after surgery or within 90 days after includes catheter removal, with replacement only if still surgery with implants; however, infections can manifest beyond necessary' these ranges. Risk factors include patient-related, procedure- (continued) related, and postoperative factors (fante 56). The patient's skin 82

Health Care-Associated lnfections TABLE 56. Mitigation of Risk Factors for Surgical Site drainage is culture negative. Organ and deep space SSIs are lnfection associated with more systemic signs and local symptoms Risk Factor lntervention related to a deep abscess or infected fluid collection. In cases Hyperglycemia of suspected organ or deep-space SSIs, CT is helpful to local- Maintain blood glucose level <180 mg/dL (10 mmol/L) during first ize the infection and determine the best approach to fluid or 48 hours after surgery abscess drainage for culture and treatment. When an SSI is lmmunosuppression Reduce doses of immunosuppressive suspected, drainage, purulent fluid, and infected tissue agents should be obtained for culture. Deep tissue or wound cul- Tobacco use Cease 30 days before surgery tures are preferable to superficial wound swab cultures that Obesity Weight loss are likely to reflect skin or wound colonization and not nec- Malnutrition Optimize nutritional status before essarily yield the causative pathogen. surgery Staphylococcus For cardiovascular and orthopedic Treatment aureus nasal surgeries, test for nasal carriage SSI treatment requires debridement of necrotic tissue, carriage 1-2 weeks before drainage of abscesses or infected fluid, and specific antimi- lf positive, decolonize using intranasal crobial therapy for organ or deep-space and deep incisional 2o/o mupirocin ointment with or without infections. Repeat debridement or drainage may be required chlorhexidine body wash to control and resolve the infection even with appropriate Skin preparation Shower the night before (soap or an antiseptic) antimicrobial therapy. When an SSI involves an implant. implant removal is preferred, followed by a prolonged course Use an alcohol-based chlorhexidine scrub at incision site of antibiotics. Superficial incisional infections can usually be managed with oral antibiotics without tissue debridement. Hair removal Do not shave site of incision Culture results guide the choice of antimicrobial agent; lf hair must be removed, it should be treatment duration varies by anatomic site and by depth of clipped as close to time of incision as possible infection. Hypothermia and Maintain perioperative normothermia hypovolemia (temperature >36'C [96.8 "F])and Prevention adequate volume replacement to Prevention is divided into preoperative, intraoperative, and ensure maximum tissue oxygen delivery postoperative measures (see Table 56). Modifiable host factors 2 "C (3.6 "F) decrease in body should be optimized before surgery. If antibiotic prophylaxis is temperature associated with threefold increase in surgical site infection indicated, select the correct agent, dose, and time for admin- istration (60 minutes before incision, 2 hours before incision lncision dressing Primarily closed incision covered with sterile dressing {or 24-48 hours for vancomycin or fluoroquinolones), and redose during sur- gery based on surgery duration and antibiotic half-life. Continuing antibiotics postoperatively does not decrease SSI and gastrointestinal or female genital tracts are major sources of incidence, even in cases of intraoperative spillage of gastroin organisms causing infection, depending on the type of surgery. testinal contents or presence of wound drains. The time during which the surgical site is open represents the period of greatest risk. Common SS I pathogens are Stop h ylococcus t(EY P0r1{rs aureus (23"1,), coagulase-negative staphyloco cci (77 "1,), entero o Most surgical site infections occur within 30 days after cocci (7'2,), E. coli (5o1,), and P aeruginoso (5'lo). Exogenous surgery or within 90 days after surgery with implants. sources of organisms (surgical personnel, surgical instruments, o Deep tissue, drainage, and purulent fluid should be environment) are less common causes of SSIs, usually identified obtained for culture in surgical site infections; Sup€r- when a cluster of infections is present. ficial wound swab cultures are likely to reflect skin or wound colonization rather than the causative Diagnosis pathogen. Clinical signs and symptoms vary by infection site and type o Surgical site infection treatment requires debridement as well as by implicated organism (for example, some are of necrotic tissue, drainage of abscesses or infected more likely to cause purulence). Inflammatory changes at the fluid, and speciflc antimicrobial therapy for organ or surgical site (pain or tenderness, warmth, swelling, ery- deep-space and deep incisional infections. thema) and purulent drainage suggest a superficial incisional . Optimizing modifiable risk factors before surgery infection. Deep incisional SSIs have more extensive tender- (hyperglycemia control, reduction of immunosuppres- ness expanding outside the area of erythema and more sys- sive agents, cessation of tobacco use, weight loss) can temic signs, such as fever and leukocytosis. Wound dehis help prevent surgical site infections. cence suggests a deep incisional SSI unless the wound or

TABLE 56. Mitigation of Risk Factors for Surgical Site drainage is culture negative. Organ and deep space SSIs are lnfection associated with more systemic signs and local symptoms Risk Factor lntervention related to a deep abscess or infected fluid collection. In cases Hyperglycemia of suspected organ or deep-space SSIs, CT is helpful to local- Maintain blood glucose level <180 mg/dL (10 mmol/L) during first ize the infection and determine the best approach to fluid or 48 hours after surgery abscess drainage for culture and treatment. When an SSI is lmmunosuppression Reduce doses of immunosuppressive suspected, drainage, purulent fluid, and infected tissue agents should be obtained for culture. Deep tissue or wound cul- Tobacco use Cease 30 days before surgery tures are preferable to superficial wound swab cultures that Obesity Weight loss are likely to reflect skin or wound colonization and not nec- Malnutrition Optimize nutritional status before essarily yield the causative pathogen. surgery Staphylococcus For cardiovascular and orthopedic Treatment aureus nasal surgeries, test for nasal carriage SSI treatment requires debridement of necrotic tissue, carriage 1-2 weeks before drainage of abscesses or infected fluid, and specific antimi- lf positive, decolonize using intranasal crobial therapy for organ or deep-space and deep incisional 2o/o mupirocin ointment with or without infections. Repeat debridement or drainage may be required chlorhexidine body wash to control and resolve the infection even with appropriate Skin preparation Shower the night before (soap or an antiseptic) antimicrobial therapy. When an SSI involves an implant. implant removal is preferred, followed by a prolonged course Use an alcohol-based chlorhexidine scrub at incision site of antibiotics. Superficial incisional infections can usually be managed with oral antibiotics without tissue debridement. Hair removal Do not shave site of incision Culture results guide the choice of antimicrobial agent; lf hair must be removed, it should be treatment duration varies by anatomic site and by depth of clipped as close to time of incision as possible infection. Hypothermia and Maintain perioperative normothermia hypovolemia (temperature >36'C [96.8 "F])and Prevention adequate volume replacement to Prevention is divided into preoperative, intraoperative, and ensure maximum tissue oxygen delivery postoperative measures (see Table 56). Modifiable host factors 2 "C (3.6 "F) decrease in body should be optimized before surgery. If antibiotic prophylaxis is temperature associated with threefold increase in surgical site infection indicated, select the correct agent, dose, and time for admin- istration (60 minutes before incision, 2 hours before incision lncision dressing Primarily closed incision covered with sterile dressing {or 24-48 hours for vancomycin or fluoroquinolones), and redose during sur- gery based on surgery duration and antibiotic half-life. Continuing antibiotics postoperatively does not decrease SSI and gastrointestinal or female genital tracts are major sources of incidence, even in cases of intraoperative spillage of gastroin organisms causing infection, depending on the type of surgery. testinal contents or presence of wound drains. The time during which the surgical site is open represents the period of greatest risk. Common SS I pathogens are Stop h ylococcus t(EY P0r1{rs aureus (23"1,), coagulase-negative staphyloco cci (77 "1,), entero o Most surgical site infections occur within 30 days after cocci (7'2,), E. coli (5o1,), and P aeruginoso (5'lo). Exogenous surgery or within 90 days after surgery with implants. sources of organisms (surgical personnel, surgical instruments, o Deep tissue, drainage, and purulent fluid should be environment) are less common causes of SSIs, usually identified obtained for culture in surgical site infections; Sup€r- when a cluster of infections is present. ficial wound swab cultures are likely to reflect skin or wound colonization rather than the causative Diagnosis pathogen. Clinical signs and symptoms vary by infection site and type o Surgical site infection treatment requires debridement as well as by implicated organism (for example, some are of necrotic tissue, drainage of abscesses or infected more likely to cause purulence). Inflammatory changes at the fluid, and speciflc antimicrobial therapy for organ or surgical site (pain or tenderness, warmth, swelling, ery- deep-space and deep incisional infections. thema) and purulent drainage suggest a superficial incisional . Optimizing modifiable risk factors before surgery infection. Deep incisional SSIs have more extensive tender- (hyperglycemia control, reduction of immunosuppres- ness expanding outside the area of erythema and more sys- sive agents, cessation of tobacco use, weight loss) can temic signs, such as fever and leukocytosis. Wound dehis help prevent surgical site infections. cence suggests a deep incisional SSI unless the wound or 83