- The greatest burden of infectious diarrhea occurs in low and middle income countries, where inadequate sanitation and hygiene are prevalent.
- Nonetheless, economic development also creates opportunities for introduction and transmission of enteric pathogens, including global travel, food importations, mass production and distribution of food, municipal water systems serving large segments of the population, and widespread use of childcare, long-term care, and recreational water facilities.
- Other risk factors include hospitalization, animal exposures, especially in public venues, as well as certain sexual practices (Figure 1).
- Acute gastroenteritis is a frequent cause of outpatient visits and hospitalizations in the United States, with an estimated annual burden of 179 million outpatient visits, nearly 500,000 hospitalizations, and over 5,000 deaths.
- Norovirus and Salmonella enterica subspecies were the leading pathogens among the 24 gastroenteritis pathogens transmissible by food that were assessed. Whereas norovirus (58%) exceeded S. enterica subspecies (11%) as a cause of illness, S. enterica subspecies exceeded norovirus as a cause of hospitalization (35% versus 28%) and death (28% versus 11%).
- Rotavirus was the most common pathogen among children younger than 5 years before rotavirus vaccine introduction.
- Highly effective measures are available to prevent and treat diarrheal disease and its complications. Avoiding dehydration by ensuring adequate fluid and electrolyte intake for replacement and maintenance is the mainstay of diarrheal illness management. Increasing resistance to antimicrobial agents and risk of worsening illness (such as diarrhea associated with Clostridium difficile) can result from antimicrobial and antimotility drug use and highlight the need for appropriate use of these interventions.
- Most acute diarrhea episodes in previously healthy, immunocompetent people are of short duration and self-resolving, and are of viral or unknown etiology. Therefore, laboratory investigation generally is not warranted. However, many factors may justify the expense and complexity of laboratory testing including epidemiologic (Table 1) and clinical features (Table 2) which encompass diarrhea in immunocompromised people, noninfectious and extraintestinal manifestations associated with enteric pathogens (Table 4) the potential for results of laboratory investigation to impact management, and suspicion of an outbreak situation.
Clinical, Demographic, and Epidemiologic Features
- A detailed clinical and exposure history should be obtained from people with diarrhea under any circumstances, including when there is a history of similar illness in others (S-M) (Figure 1).
- People with diarrhea who attend or work in child care centers, long-term care facilities, patient care, food service, or recreational water venues (e.g., pools and lakes) should follow jurisdictional recommendations for outbreak reporting and infection control (S-H).
- People with fever or bloody diarrhea should be evaluated for enteropathogens for which antimicrobial agents may confer clinical benefit, including S. enterica subspecies, Shigella, and Campylobacter (S-L).
- Enteric fever should be considered when a febrile person (with or without diarrhea) has a history of travel to areas in which causative agents are endemic, has consumed foods prepared by people with recent endemic exposure or has laboratory exposure to S. enterica subspecies enterica serovar Typhi and S. enterica subspecies enterica serovar Paratyphi (S-M). In this document, S. Typhi represents the more formal and detailed name S. enterica subspecies enterica serovar Typhi, and Salmonella Paratyphi corresponds to the Paratyphi serovar.
- People of all ages with acute diarrhea should be evaluated for dehydration, which increases the risk of life-threatening illness and death especially among the young and older adults (S-H).
- When the clinical or epidemic history suggests a possible Shiga-toxin producing organism, diagnostic approaches should be applied that detect Shiga toxin (or the genes that encode them) and distinguish Escherichia coli O157:H7 from other Shiga toxin producing E. coli (STEC) in stool (S-M). If available, diagnostic approaches that can distinguish between Shiga toxin 1 and Shiga toxin 2, which is typically more potent, could be used (W-M). In addition, Shigella dysenteriae type 1, and rarely, other pathogens may produce Shiga toxin and should be considered as a cause of hemolytic uremic syndrome (HUS), especially in people with suggestive international travel or personal contact with a traveler (S-M).
- Clinicians should evaluate people for post-infectious and extraintestinal manifestations associated with enteric infections (S-M) (Table 4).
- Stool testing should be performed for Salmonella, Shigella, Campylobacter, Yersinia, C. difficile and STEC in people with diarrhea accompanied by fever, bloody or mucoid stools, severe abdominal cramping or tenderness, or signs of sepsis (S-M). Bloody stools are not an expected manifestation of infection with C. difficile. STEC O157 should be assessed by culture and non-O157 STEC should be detected by Shiga toxin or genomic assays (S-L). Sorbitol-MacConkey agar or an appropriate chromogenic agar alternative is recommended to screen for O157:H7 STEC; detection of Shiga toxin is needed to detect other STEC serotype (S-M).
- Blood cultures should be obtained from infants <3 months of age, people of any age with signs of septicemia or when enteric fever is suspected, systemic manifestations of infection, people who are immunocompromised, people with certain high-risk conditions such as hemolytic anemia, and people who traveled to or have had contact with travelers from enteric fever-endemic areas with a febrile illness of unknown etiology (S-M).
- Stool testing should be performed under clearly identified circumstances (Table 1) for Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, and STEC in symptomatic hosts (S-L). Specifically: a. Test for Yersinia enterocolitica in people with persistent abdominal pain (especially school-aged children with right lower quadrant pain mimicking appendicitis who may have mesenteric adenitis), and in people with fever at epidemiologic risk for yersiniosis, including infants with direct or indirect exposures to raw or undercooked pork products. b. In addition, test stool specimens for Vibrio species in people with large volume rice water stools or either exposure to salty or brackish waters, consumption of raw or undercooked shellfish, or travel to cholera-endemic regions within 3 days prior to onset of diarrhea.
- A broader set of bacterial, viral, and parasitic agents should be considered regardless of the presence of fever, bloody or mucoid stools, or other markers of more severe illness in the context of a possible outbreak of diarrheal illness (e.g., multiple people with diarrhea who shared a common meal or a sudden rise in observed diarrheal cases). Selection of agents for testing should be based on a combination of host and epidemiologic risk factors and ideally in coordination with public health authorities (S-M).
- A broad differential diagnosis is recommended in immunocompromised people with diarrhea, especially those with moderate and severe primary or secondary immune deficiencies, for evaluation of stool specimens by culture, viral studies, and examination for parasites (S-M). People with acquired immune deficiency syndrome (AIDS) with persistent diarrhea should undergo additional testing for other organisms including, but not limited to, Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus (CMV) (S-M).
- Diagnostic testing is not recommended in most cases of uncomplicated travelers’ diarrhea (TD) unless treatment is indicated. Travelers with diarrhea lasting ≥14 days should be evaluated for intestinal parasitic infections (S-M). Testing for C. difficile should be performed in travelers treated with antimicrobial agent(s) within the preceding 8–12 weeks. In addition, gastrointestinal tract disease including inflammatory bowel disease (IBD) and post-infectious irritable bowel syndrome (IBS) should be considered for evaluation (S-M).
- Clinical consideration should be included in the interpretation of results of multiple pathogen nucleic acid amplification tests (MP-NAAT) because these assays detect DNA and not necessarily viable organisms (S-L).
- All specimens that test positive for bacterial pathogens by culture independent diagnostic testing (CIDT) such as antigen-based molecular assays (gastrointestinal tract panels), and for which isolate submission is requested or required under public health reporting rules, should be cultured in the clinical laboratory or at a public health laboratory to ensure that outbreaks of similar organisms are detected and investigated (S-L). Also, a culture may be required in situations where antimicrobial susceptibility testing results would affect care or public health responses (S-L).
- Specimens from people involved in an outbreak of enteric disease should be tested for enteric pathogens per public health department guidance (S-L).
- Culture-independent, including panel based multiplex molecular diagnostics from stool and blood specimens, and, when indicated, culture-dependent diagnostic testing should be performed when there is a clinical suspicion of enteric fever (diarrhea uncommon) or diarrhea with bacteremia (S-M). Additionally, cultures of bone marrow (particularly valuable if antimicrobial agents have been administered), stool, duodenal fluid, and urine may be beneficial to detect enteric fever (W-M). Serologic tests should not be used to diagnose enteric fever (S-M).
- Testing may be considered for C. difficile in people over 2 years of age who have a history of diarrhea following antimicrobial use and in people with healthcare associated diarrhea (W-H). Testing for C. difficile may be considered in people who have persistent diarrhea without an etiology and without recognized risk factors (W-L). A single diarrheal stool specimen is recommended for detection of toxin or a toxigenic C. difficile strain (e.g., NAAT testing) (S-L).
- Multiple specimens do not increase yield.
- The optimal specimen for laboratory diagnosis of infectious diarrhea is a diarrheal stool sample (i.e., a sample that takes the shape of the container). For detection of bacterial infections, if a timely diarrheal stool sample cannot be collected, a rectal swab may be used (W-L). Molecular techniques generally are more sensitive and less dependent than culture on the quality of specimen. For identification of viral and protozoal agents and C. difficile toxin, fresh stool is preferred (W-L).
- Fecal leukocyte examination and stool lactoferrin detection should NOT be used to establish the cause of acute infectious diarrhea (S-M).
- There are insufficient data available to make a recommendation on the value of fecal calprotectin measurement in people with acute infectious diarrhea.
- Serologic tests are NOT recommended to establish an etiology of infectious diarrhea or enteric fever (S-L) but may be considered for people with post-diarrheal HUS in which a stool culture did not yield a Shiga toxin-producing organism (W-L).
- A peripheral white blood cell count and differential and serologic assays should NOT be performed to establish an etiology of diarrhea (S-L), but may be useful clinically (W-L).
- Frequent monitoring of hemoglobin and platelet counts, electrolytes, and blood urea nitrogen and creatinine is recommended to detect hematologic and renal function abnormalities that are early manifestations of HUS and precede renal injury for people with diagnosed E. coli O157 or another STEC infection (especially STEC that produce Shiga toxin 2 or are associated with bloody diarrhea) (S-H). Examining a peripheral blood smear for the presence of red blood cell fragments is necessary when HUS is suspected (S-H).
- Endoscopy or proctoscopic examination should be considered in people with persistent, unexplained diarrhea who have AIDS, in people with certain underlying medical conditions as well as people with acute diarrhea with clinical colitis or proctitis and in people with persistent diarrhea who engage in anal intercourse (S-L). Duodenal aspirate may be considered in select people for diagnosis of suspected Giardia, Strongyloides, Cystoisospora, or microsporidia infection (W-L).
- Imaging (e.g., ultrasonography, computed tomography [CT], or magnetic resonance imaging [MRI]) may be considered to detect aortitis, mycotic aneurysms, signs and symptoms of peritonitis, intraabdominal free air, toxic megacolon, or extravascular foci of infection in older people with invasive S. enterica or Yersinia infections if there is sustained fever or bacteremia despite adequate antimicrobial therapy or if the patient has underlying atherosclerosis or has recent-onset chest, back, or abdominal pain (W-L).
- Follow-up testing is not recommended in most people for case management following resolution of diarrhea (S-M). Collection and analysis of serial stool specimens using culture-dependent methods for S. enterica subspecies enterica serovar Typhi or S. enterica subspecies enterica serovar Paratyphi, STEC, Shigella, non-typhoidal Salmonella, and other bacterial pathogens are recommended in certain situations by local health authorities following cessation of diarrhea to enable return to child care, employment or group social activities (S-M). Practitioners should collaborate with local public health authorities to adhere to policies regarding return to settings in which transmission is a consideration (S-H).
- A clinical and laboratory re-evaluation may be indicated in people who do not respond to an initial course of therapy and should include consideration of noninfectious conditions including lactose intolerance (W-L).
- Non-infectious conditions, including IBD and IBS, should be considered as underlying etiologies in people with symptoms lasting ≥14 days and unidentified sources (S-M).
- Reassessment of fluid and electrolyte balance, nutritional status, and optimal dose and duration of antimicrobial therapy is recommended in people with persistent symptoms (S-H). (Figure 1)
Table 1. Exposure or Condition Associated with Pathogens Causing Diarrhea
|Exposure or Condition||Pathogen(s)|
|Foodborne outbreaks in hotels, cruise ships, resorts, restaurants, catered events||Norovirus, non-typhoidal Salmonella, C. perfringens,|
B. cereus, S. aureus, Campylobacter spp. Enterotoxigenic E. coli (ETEC), STEC, Listeria, Shigella, Cyclospora cayetanensis, Cryptosporidium spp.
|Consumption of unpasteurized milk or dairy products||Salmonella, Campylobacter, Yersinia enterocolitica,|
S. aureus toxin, Cryptosporidium, and STEC. Listeria is infrequently associated with diarrhea, Brucella (goat milk cheese), M. bovis, Coxiella burnetti
|Consumption of raw or undercooked meat or poultry||STEC (beef), C. perfringens (beef, poultry), Salmonella (poultry), Campylobacter (poultry), Yersinia (pork, chitterlings), S. aureus (poultry), and Trichinella spp. (pork, wild game meat)|
|Consumption of fruits or unpasteurized fruit juices, vegetables, leafy greens, and sprouts||STEC, non-typhoidal Salmonella, Cyclospora, Cryptosporidium, norovirus, hepatitis A, and Listeria monocytogenes|
|Consumption of undercooked eggs||Salmonella, Shigella (egg salad)|
|Consumption of raw shellfish||Vibrio species, norovirus, hepatitis A, Plesiomonas|
|Exposure or Contact|
|Swimming in or drinking untreated fresh water||Campylobacter, Cryptosporidium, Giardia, Shigella, Salmonella, STEC , Plesiomonas shigelloides|
|Swimming in recreational water facility with treated water||Cryptosporidium and other potentially waterborne pathogens when disinfectant concentrations are inadequately maintained|
|Healthcare, long-term care, prison exposure or employment||Norovirus, C. difficile, Shigella, Cryptosporidium, Giardia, STEC, rotavirus|
|Child care center attendance or employment||Rotavirus, Cryptosporidium, Giardia, Shigella, STEC|
|Recent antimicrobial therapy||C. difficile, multidrug resistant Salmonella|
|Travel to resource-challenged countries||E. coli (Enteroaggregative, Enterotoxigenic, Enteroinvasive), Shigella, Typhi and nontyphoid Salmonella, Campylobacter, Vibrio cholerae, Entamoeba histolytica, Giardia, Blastocystis, Cyclospora, Cystoisospora, Cryptosporidium|
|Exposure to house pets with diarrhea||Campylobacter, Yersinia|
|Exposure to pig feces in certain parts of the world||Balantidium coli|
|Contact with young poultry or reptiles||Non-typhoidal Salmonella|
|Visiting a farm or petting zoo||STEC, Cryptosporidium, Campylobacter|
|Age group||Rotavirus (6–18 months of age), non-typhoidal Salmonella (infants from birth to 3 months of age and adults >50 years with a history of atherosclerosis), Shigella (1–7 years of age), Campylobacter (young adults)|
|Underlying immunocompromising condition||Non-typhoidal Salmonella, Cryptosporidium, Campylobacter, Shigella, Yersinia|
|Hemochromatosis or hemoglobinopathy||Yersinia enterocolitica, Salmonella|
|AIDS, immunosuppressive therapies||Cryptosporidum, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium-intercellular complex, cytomegalovirus|
|Anal-genital, oral-anal, or digital-anal contact||Shigella, Salmonella, Campylobacter, E. histolytica, Giardia lamblia, Cryptosporidium as well as sexually transmitted infections|
Table 2. Clinical Presentations Suggestive of Infectious Diarrhea Etiologies
|Persistent or chronic diarrhea||Cryptosporidium spp., Giardia lamblia, Cyclospora cayetanensis, Cystoisospora belli, and Entamoeba histolytica|
|Visible blood in stool||STEC, Shigella, Salmonella, Campylobacter, Entamoeba histolytica, non-Cholera Vibrio species, Yersinia, Balantidium coli, Plesiomonas|
|Fever||Not highly discriminatory-viral, bacterial and parasitic infections can cause fever. In general, higher temperatures are suggestive of bacterial etiology or E. histolytica . Patients infected with STEC usually are not febrile at time of presentation.|
|Abdominal pain||STEC, Salmonella, Shigella, Campylobacter, Yersinia, non-cholera Vibrio species, C. difficile|
|Severe abdominal pain, often grossly blood stools (occasionally non-bloody), and minimal or no fever||STEC, Salmonella, Shigella, Campylobacter, and Yersinia enterocolitica|
|Persistent abdominal pain and fever||Yersinia enterocolitica and Y. pseudotuberculosis, may mimic appendicitis|
|Nausea and vomiting lasting ≤24 hours||Ingestion of S. aureus enterotoxin or Bacillus cereus (short-incubation emetic syndrome)|
|Diarrhea and abdominal cramping lasting 1–2 days||Ingestion of Clostridium perfringens or Bacillus cereus (long-incubation emetic syndrome)|
|Vomiting and nonbloody diarrhea lasting 2–3 days or less||Norovirus, (low-grade fever usually present during the first 24 hours in 40% if infections)|
|Chronic watery diarrhea, often lasting a year or more||Brainerd diarrhea (etiologic agent has not been identified); post-infectious irritable bowel syndrome|
Table 3. Laboratory Diagnostics for Organisms Associated with Infectious Diarrhea*
|Etiologic Agents||Diagnostic Procedures||Optimal Specimen**|
|C. difficile||Nucleic acid amplification test (NAAT)||Stool|
|Glutamate dehydrogenase (GDH) antigen with or without toxin detection followed by cytotoxin or C. difficile toxin or toxigenic C. difficile strain.|
|Salmonella enterica, Shigella spp, Campylobacter spp||Routine stool enteric pathogen culturea or NAAT||Stool|
|Salmonella enterica serovar Typhi and Paratyphi (enteric fever)||Routine culture||Stool, blood, bone marrow, and duodenal fluid|
|Shiga-toxin-producing E. coli||Culture for E. coli O157:H7 b and Shiga-toxin immunoassay or NAAT for Shiga toxin genes||Stool|
|Yersinia spp, Plesiomonas spp, Edwardsiella tarda, S. aureus E. coli: enterotoxigenic enteroinvasive enteropathogenic enteroaggregative||Specialized stool culture or molecular assays c or NAAT||Stool|
|Clostridium perfringens||Specialized procedure for toxin detection d||Stool|
|Specialized procedure for toxin detection d||Food|
|Clostridium botulinum||Mouse lethality assay (performed at a State Public Health Laboratory, or CDC) e,f,g||Serum, stool, gastric contents, vomitus|
Entamoeba histolytica Blastocystis homini h Dientamoeba fragilis h Balantidium coli Giardia lamblia
Nematodes (generally not associated with diarrhea) including: Ascaris lumbricoides, Strongyloides stercoralisi, Trichuris trichiura, Hookworms Cestodes (tapeworms) Trematodes (flukes)
|Ova and parasite examination including permanent stained smeari or NAAT||Duodenal fluid for Giardia and Strongyloides|
|E. histolytica||E. histolytica species-specific immunoassay or NAAT||Stool|
|Giardia lamblia j||Enzyme immunoassay (EIA) or NAAT||Stool|
|Cryptosporidium spp j||Direct fluorescent immunoassay, EIA or NAAT||Stool|
|Cyclospora cayetanensis and Cystoisospora bellik||Modified acid fast stain k performed on concentrated specimen, ultraviolet fluorescence microscopy, or NAAT||Stool|
|Microsporidia (now classified as a fungus)||Modified trichrome stain k performed on concentrated specimen||Stool|
|Histologic examination with electron microscopic confirmation||Small bowel biopsy|
|Calicivirus (Norovirus, Sapovirus) k Enteric Adenovirus Enterovirus/Parechovirus k Rotavirus||NAAT||Stool|
|Rotavirus Enteric Adenovirus||Enzyme immunoassay||Stool|
|Enteric Adenovirus l Enterovirus/Parechovirus||Viral culture||Stool|
|Cytomegalovirus (CMV)||Histopathological examination||Biopsy|
* The field of rapid diagnostic testing is rapidly expanding. We expect that additional diagnostic assays will become available following publication of these guidelines, specifically panel-based molecular diagnostics, including NAAT.
** Contact laboratory for instructions regarding container, temperature and transport guidelines to optimize results.
a Routine stool culture in most laboratories is designed to detect Salmonella spp, Shigella spp, Campylobacter spp and E. coli O157 or Shiga-toxin producing E. coli, but this should be confirmed with the testing laboratory.
b It is recommended that laboratories routinely process all stool specimens submitted for bacterial culture for the presence of Shiga-toxin-producing strains of E. coli including O157:H7. However, in some laboratories, O157:H7 testing is performed only by specific request.
c Specialized cultures or molecular assays may be required to detect these organisms in stool specimens. The laboratory should be notified whenever there is a suspicion of infection due to one of these pathogens.
d Bacillus cereus, Clostridium perfringens and Staphylococcus aureus are associated with diarrheal syndromes that are toxin mediated. An etiologic diagnosis is made by demonstration of toxin in stool for Clostridium perfringens and demonstration of toxin in food for Bacillus cereus and Staphylococcus aureus.
e Toxin assays are either performed in public health laboratories or referred to laboratories specializing in such assays.
f Testing for Clostridium botulinum toxin is either performed in public health laboratories or referred to laboratories specializing in such testing. The toxin is lethal, and special precautions are required for handling. Class A bioterrorism agent and rapid sentinel laboratory reporting schemes must be followed. Immediate notification of a suspected infection to the state health department is mandated.
g Implicated food materials may also be examined for C. botulinum toxin, but most hospital laboratories are not equipped for food analysis.
h The pathogenicity of Blastocystis hominis and Dientamoeba fragilis remains controversial. In the absence of other pathogens, they may be clinically relevant if symptoms persist. Reporting semi-quantitative results (rare, few, many) may help determine significance and is a College of American Pathologists accreditation requirement for participating laboratories.
i Detection of Strongyloides in stool may require the use of Baermann technique or agar plate culture.
j Cryptosporidium and Giardia lamblia testing is often offered and performed together as the primary parasitology examination. Further studies should follow if the epidemiologic setting or clinical manifestations suggest parasitic disease.
k These stains may not be routinely available.
l Enteric adenoviruses may not be recovered in routine viral culture.
Empiric Management of Infectious Diarrhea
- In immunocompetent children and adults, empiric antimicrobial therapy for bloody diarrhea while waiting for results of investigations is NOT recommended (S-L), except for the following:
- Infants <3 months of age with suspicion of a bacterial etiology.
- Ill immunocompetent people with fever documented in a medical setting, abdominal pain, bloody diarrhea, and bacillary dysentery (frequent scant bloody stools, fever, abdominal cramps, tenesmus) presumptively due to Shigella.
- People who have recently travelled internationally with body temperatures >38.5° Celsius and/or signs of sepsis (W-L). (https://wwwnc.cdc.gov/travel/yellowbook/2016/the-pre-travel-consultation/travelers-diarrhea)
- The empiric antimicrobial therapy in adults should be either a fluoroquinolone such as ciprofloxacin, or azithromycin, depending on the local susceptibility patterns and travel history (S-M). Empiric therapy for children includes a third generation cephalosporin for infants <3 months of age and others with neurologic involvement, or azithromycin, depending on local susceptibility patterns and travel history (S-M).
- Empiric antibacterial treatment should be considered in immunocompromised people with severe illness and bloody diarrhea (S-L).
- Asymptomatic contacts of people with bloody diarrhea should not be offered empiric treatment but should be advised to follow appropriate infection prevention and control measures (S-M).
- People with clinical features of sepsis who are suspected of having enteric fever should be treated empirically with broad-spectrum antimicrobial therapy after blood, stool, and urine culture collection (S-L). Antimicrobial therapy should be narrowed when antimicrobial susceptibility testing results become available (S-H). If an isolate is unavailable and there is a clinical suspicion of enteric fever, antimicrobial choice may be tailored to susceptible patterns from the setting where acquisition occurred (W-L).
- Antimicrobial therapy for people with infections attributed to STEC O157 and other STEC that produce Shiga toxin 2 (or if the toxin genotype is unknown) should be avoided (S-M). Antimicrobial therapy for people with infections attributed to other STEC that do not produce Shiga toxin 2 (generally non-O157 STEC) is debatable due to insufficient evidence of benefit or the potential harm associated with some classes of antimicrobial agents (S-L).
- In most people with acute watery diarrhea and without recent international travel, empiric antimicrobial therapy is not recommended (S-L). An exception may be made in people who are immunocompromised or young infants who are ill-appearing. Empiric treatment should be avoided in people with persistent
watery diarrhea >14 days or more (S-L).
- Asymptomatic contacts of people with acute or persistent watery diarrhea should not be offered empiric or preventive therapy but should be advised to follow appropriate infection prevention and control measures (S-M).
Directed Management of Infectious Diarrhea
- Antimicrobial treatment should be modified or discontinued when a clinically plausible organism is identified (S-H) (Table 5).
- Reduced osmolarity oral rehydration solution (ORS) is recommended as the first-line therapy of mild to moderate dehydration in infants, children, and adults with acute diarrhea from any cause (S-M) and in people with mild to moderate dehydration associated with vomiting or severe diarrhea.
- Nasogastric administration of ORS may be considered in infants, children, and adults with moderate dehydration who cannot tolerate oral intake, or in children with normal mental status who are too weak or refuse to drink adequately (W-L).
- Isotonic intravenous fluids such as lactated Ringer’s and normal saline solution should be administered when there is severe dehydration, shock, or altered mental status and failure of ORS therapy (S-H) or ileus (S-M). In people with ketonemia, an initial course of intravenous hydration may be needed to enable tolerance of oral rehydration (W-L).
- In severe dehydration, intravenous rehydration should be continued until pulse, perfusion and mental status normalizes, patient awakens and has no risk factors for aspiration and no evidence of ileus (S-L). The remaining deficit can be replaced by using ORS (W-L). Infants, children, and adults with mild-to-moderate dehydration should receive ORS until clinical dehydration is corrected (S-L).
- Once the patient is rehydrated, maintenance fluids should be administered. Replace ongoing losses in stools from infants, children, and adults with ORS, until diarrhea and vomiting are resolved (S-L).
- Human milk feeding should be continued in infants and children throughout the diarrheal episode (S-L).
- Resumption of an age-appropriate usual diet is recommended during or immediately after the rehydration process is completed (S-L).
- Ancillary treatment with antimotility, antinausea, or antiemetic agents can be considered once the patient is adequately hydrated, but their use is not a substitute for fluid and electrolyte therapy (W-L).
- Antimotility drugs (e.g., loperamide) should not be given to children <18 years of age with acute diarrhea (S-M). Loperamide may be given to immunocompetent adults with acute watery diarrhea (W-M) but should be avoided at any age in suspected or proven cases where toxic megacolon may result in inflammatory diarrhea or diarrhea with fever (S-L).
- Antinausea and antiemetic (e.g., ondansetron) drugs may be given to facilitate tolerance of oral rehydration in children >4 years of age and in adolescents with acute gastroenteritis associated with vomiting (W-M).
- Probiotic preparations may be offered to reduce the symptom severity and duration in immunocompetent adults and children with infectious or antimicrobial-associated diarrhea (W-M).
- Specific recommendations regarding selection of probiotic organism(s), route of delivery and dose may be found through literature searches of studies and through guidance from manufacturers.
- Oral zinc supplementation reduces the duration of diarrhea in children 6 months to 5 years of age who reside in countries with a high prevalence of zinc deficiency or who have signs of malnutrition (S-M).
- Asymptomatic people who practice hand hygiene and live and work in low-risk settings (do not provide healthcare, child or elderly adult care and are not food service employees) do not need treatment except asymptomatic people with S. enterica subspecies enterica serovar Typhi in their stool who may be treated empirically to reduce potential for transmission (W-L). Asymptomatic people who practice hand hygiene and live and work in high-risk settings (provide healthcare, child or elderly adult care and are food service employees) should be treated according to local public health guidance (S-H).
- Hand hygiene should be performed after using the toilet, changing diapers, before and after preparing food, before eating, after handling garbage or soiled laundry items, and after touching animals or their feces or environments, especially in public settings such as petting zoos (S-M).
- Infection control measures including use of gloves and gowns, hand hygiene with soap and water, or alcohol-based sanitizers should be followed in the care of people with diarrhea (S-H). The selection of a hand hygiene product should be based upon a known or suspected pathogen and the environment in which the organism may be transmitted (S-L). Refer to https://www.cdc.gov/hicpac/2007IP/2007isolationPrecautions.html
- Appropriate food safety practices are recommended to avoid cross-contamination of other foods or cooking surfaces and utensils during grocery shopping, food preparation, and storage. Ensure that foods containing meats and eggs are cooked and maintained at proper temperatures (S-M).
- Health care providers should direct educational efforts towards all people with diarrhea but particularly to people with primary and secondary immune deficiencies, pregnant women, parents of young children, and the elderly since they have increased risk of complications from diarrheal disease (S-L).
- Ill people with diarrhea should avoid swimming, water-related activities and sexual contact with other people while symptomatic and adhere to meticulous hand hygiene, (S-L).
- Rotavirus vaccine should be administered to all infants without a known contraindication (S-H).
- Two typhoid vaccines (oral and injectable) are licensed in the United States but are not recommended routinely. Typhoid vaccination is recommended as an adjunct to hand hygiene and the avoidance of high-risk foods and beverages for travelers to areas where there is moderate to high-risk for exposure to S. enterica subspecies enterica serovar Typhi, people with intimate exposure (e.g., household contact) to a documented S. enterica subspecies enterica serovar Typhi chronic carrier, and microbiologists and other laboratory personnel routinely exposed to cultures of S. enterica subspecies enterica serovar Typhi (S-H). Booster doses are recommended for people who remain at risk (S-H).
- A live attenuated cholera vaccine, which is available as a single-dose oral vaccine in the United States, is recommended for adults 18–64 years of age who travel to cholera-affected areas (S-H). https://www.cdc.gov/cholera/vaccines.html
- All diseases listed in the table of National Notifiable Diseases Surveillance System at the national level, including those that cause diarrhea, should be reported to the appropriate state, territorial, or local health department with submission of isolates of certain pathogens (e.g., Salmonella, STEC, Shigella, and Listeria) to ensure that control and prevention practices may be implemented (S-H).
Table 4. Post-infectious Manifestations Associated with Enteric Pathogens
|Erythema nodosum||Yersinia, Campylobacter, Salmonella, Shigella|
|Glomerulonephritis||Shigella, Campylobacter, Yersinia|
|Hemolytic anemia||Campylobacter, Yersinia|
|Hemolytic uremic syndrome||STEC, Shigella dysenteriae serotype 1|
|Reactive arthritis (includes Reiter syndrome)||Salmonella, Shigella, Campylobacter, Yersinia, rarely Giardia and Cyclospora cayetanensis|
|Post-infectious irritable bowel syndrome||Campylobacter, Salmonella, Shigella, STEC, Giardia|
|Meningitis||Listeria, Salmonella (infants <3 months of age are at high-risk)|
|Intestinal perforation||Salmonella including Salmonella Typhi, Shigella, Campylobacter, Yersinia, Entamoeba histolytica|
|Ekiri syndrome (lethal, toxic encephalopathy) and/or seizure||Shigella|
|Aortitis, osteomyelitis, extravascular deep tissue focus||Salmonella, Yersinia|
Table 5. Recommended Antimicrobial Agents by Pathogen
|C. difficile||Oral vancomycin||fidaxomicin||Fidaxomicin not currently recommended for people <18 years of age. Metronidazole is still acceptable treatment for non-severe CDI in children and as a second-line agent for adults with non-severe CDI (e.g., who cannot obtain vancomycin or fidaxomicin at a reasonable cost).|
|Non-typhoidal Salmonella enterica b||Usually not indicated for uncomplicated infection||N/A||Antimicrobial therapy should be considered for groups at increased risk for invasive infection: neonates (<3 months old), persons >50 years old with suspected atherosclerosis, persons with immunosuppression, cardiac (valvular or endovascular) or significant joint disease. If susceptible, treat with ceftriaxone, ciprofloxacin, TMP/SMX or amoxicillin.|
|Salmonella enterica Typhi or Paratyphi b||ceftriaxone or ciprofloxacin||ampicillin or TMP/SMX or azithromycin|
|Shigella a||azithromycin c or ciprofloxacin a, or ceftriaxone||TMP/SMX or ampicillin if susceptible||Clinicians treating people with shigellosis for whom antibiotic treatment is indicated should avoid prescribing fluoroquinolones if the ciprofloxacin MIC is ≥0.12 μg/mL even if the laboratory report identifies the isolate as susceptible. https://emergency.cdc.gov/han/han00401.asp|
|Vibrio cholerae||doxycycline d||ciprofloxacin, azithromycin, or ceftriaxone|
|Non-Vibrio cholera d||Usually not indicated for non-invasive disease. Single agent therapy for non-invasive disease if treated. Invasive disease: ceftriaxone plus doxycycline||Usually not indicated for non-invasive disease. Single agent therapy for non-invasive disease if treated. Invasive disease:|
plus an aminoglycoside
|Yersinia enterocolitica||TMP/SMX||cefotaxime or ciprofloxacin|
|Cryptosporidium spp.||nitazoxanide (HIV-uninfected, HIV-infected in combination with effective cART)||Effective cART: Immune reconstitution may lead to microbiologic and clinical response.||N/A|
|Cyclospora cayetanensis||TMP/SMX||nitazoxanide (limited data)||Patients with HIV infection may require higher doses or longer durations of TMP/SMX treatment|
|Giardia lamblia||tinidazole Note: Based on data from HIV-uninfected children nitazoxanide||metronidazole Note: Based on data from HIV-uninfected children|
|Cystoisospora belli||TMP/SMX||pyrimethamine Potential second-line alternatives:|
|Trichinella spp .||albendazole||Alternative: mebendazole||Therapy less effective in late stage of infection, when larvae encapsulate in muscle|
|Microsporidia||For disseminated (not ocular) and intestinal infection attributed to microsporidia other than E. bieneusi or V. corneae:||N/A||Effective cART therapy:|
a For information on susceptibility patterns in the United States see the National Antimicrobial Resistance Monitoring system (NARMS): http://www.cdc.gov/narms . Susceptibility testing should be considered when a therapeutic agent is selected.
b If invasive disease is suspected or confirmed, ceftriaxone is preferred over ciprofloxacin due to increasing resistance to ciprofloxacin.
c Most clinical laboratories do not test for azithromycin susceptibility.
d Primary therapy is aggressive rehydration; antibiotics are adjunctive therapy.
Table 6. Fluid and Nutritional Management of Diarrhea
|Degree of dehydrationa||Rehydration therapy||Replacement of losses during maintenancec|
|Mild to moderate dehydration|
Infantsb and children: ORS, 50–100 mL/kg over 3–4 hours.
Adolescents and adults (≥30 kg): ORS 2-4 liters
|Infants and children:|
Infants: Malnourished infants may benefit from frequent, smaller-volume boluses of 10 mL/kg body weight due to reduced capacity to increase cardiac output with larger volume resuscitation.
Children, adolescents, and adults: Intravenous isotonic crystalloid boluses per current fluid resuscitation guidelines, until pulse, perfusion, and mental status return to normal. Adjust electrolytes and administer dextrose based on chemistry values. Administer up to 20 mL/kg body weight until pulse, perfusion, and mental status return to normal.
|Infants and children:|
Low osmolarity ORS can be given to all age groups with any cause of diarrhea. It is safe in the presence of hypernatremia as well as hyponatremia (except when edema is present). Some commercially available formulations that can be used as ORS include Pedialyte® Liters (Abbott Nutrition), CeraLyte® (Cero Products), and Enfalac Lytren® (Mead Johnson). Popular beverages that should not be used for rehydration include apple juice, Gatorade, and commercial soft drinks.
a A variety of scales are available to grade the severity of dehydration in young children but no single, standard, validated method exists. Note that signs of dehydration may be masked when a child is hypernatremic.
b Breastfed infants should continue nursing throughout the illness.
c After rehydration is complete, maintenance fluids should be resumed along with an age-appropriate normal diet offered every 3-4 hours. Children previously receiving a lactose-containing formula can tolerate the same product in most instances. Diluted formula does not appear to confer any benefit.
Adapted from Centers for Disease Control and prevention. Managing acute gastroenteritis among children: oral rehydration, maintenance, and Nutritional Therapy. MMWR 2003;52(RR16):1-16 and WHO. The Treatment of Diarrhoea: A manual for physicians and other senior health workers: ( https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5216a1.htm)