Table of Contents

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea

Published CID, 10/19/2017
Clinical Infectious Diseases, bulk 65, Issue 12, 29 November 2017, Pages e45–e80, hypertext transfer protocol : //doi.org/10.1093/cid/cix669
Published : 19 October 2017
Andi L Shane, MD, Rajal K Mody, MD, John A Crump, MD Phillip I Tar, Theodore S Steiner, MD Karen Kotloff, MD, Joanne M Langley, MD, Christine Wanke, MD, Cirle Alcantara Warren, MD, Allen C Cheng, PhD, Joseph Cantey, MD, Larry K Pickering, MD.

For full document, including tables and references, please visit the Oxford University Press web site .
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Abstract

These guidelines are intended for use by healthcare professionals who care for children and adults with suspect or confirmed infectious diarrhea. They are not intended to replace doctor opinion regarding specific patients or clinical or populace health situations. This document does not provide detail recommendations on contagion prevention and control condition aspects related to infectious diarrhea .
Keywords: diarrhea, infectious, diagnostics, management, prevention

Executive Summary

The following evidence-based guidelines for management of infants, children, adolescents, and adults in the United States with acute or persistent infectious diarrhea were prepared by an adept panel assembled by the infectious Diseases Society of America ( IDSA ) and replace guidelines published in 2001 [ 1 ]. Public health aspects of diarrhea associated with foodborne and waterborne diarrhea, external travel, antimicrobial agents, immunocompromised hosts, animal exposure, certain sexual practices, healthcare-associated diarrheal infections, and infections acquired in childcare and long-run care facilities will be referred to in these guidelines, but are not covered extensively due to handiness of detail discussions of this information in other publications. For recommendations pertaining to Clostridium difficile, refer to the existing IDSA/Society for Healthcare Epidemiology of America ( SHEA ) guidelines on C. difficile infections, which are in the action of being updated .
Summarized under are recommendations made in the update guidelines for diagnosis and management of infectious diarrhea. The Panel followed a process used in exploitation of other IDSA guidelines [ 2 ] which included a taxonomic burden of the strength of recommendation and quality of evidence using GRADE ( Grading of Recommendations Assessment, Development and Evaluation ) [ 3–7 ]. A detail description of the methods, background, and evidence summaries that support each of the recommendations can be found on-line in the full text of the guidelines .

Recommendations (Abridged)

Clinical, Demographic, and Epidemiologic Features

I. In people with diarrhea, which clinical, demographic, or epidemiologic features have diagnostic or management implications? (Tables 1–3)

  1. 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 (strong, moderate).
  2. People with diarrhea who attend or work in child care centers, long-term care facilities, patient care, food service, or recreational water venues (eg, pools and lakes) should follow jurisdictional recommendations for outbreak reporting and infection control (strong, high).

II. In people with fever or bloody diarrhea, which clinical, demographic, or epidemiologic features have diagnostic or management implications? (Tables 1–3)

  1. People with fever or bloody diarrhea should be evaluated for enteropathogens for which antimicrobial agents may confer clinical benefit, including Salmonella enterica subspecies, Shigella, and Campylobacter (strong, low).
  2. 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 had consumed foods prepared by people with recent endemic exposure, or has laboratory exposure to Salmonella enterica subspecies enterica serovar Typhi and Salmonella enterica subspecies enterica serovar Paratyphi (strong, moderate). In this document, Salmonella Typhi represents the more formal and detailed name Salmonella enterica subspecies enterica serovar Typhi, and Salmonella Paratyphi corresponds to the Paratyphi serovar.

III. What clinical, demographic, or epidemiologic features are associated with complications or severe disease? (Tables 2 and 3)

  1. 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 (strong, high).
  2. 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 (strong, moderate). If available, diagnostic approaches that can distinguish between Shiga toxin 1 and Shiga toxin 2, which is typically more potent, could be used (weak, moderate). 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 (strong, moderate).
  3. Clinicians should evaluate people for postinfectious and extraintestinal manifestations associated with enteric infections (strong, moderate) [8].

Diagnostics

IV. Which pathogens should be considered in people presenting with diarrheal illnesses, and which diagnostic tests will aid in organism identification or outbreak investigation?

  1. 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 (strong, moderate). 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 (strong, low). 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 (strong, moderate).
  2. 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, people with 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 (strong, moderate).
  3. Stool testing should be performed under clearly identified circumstances (Table 2) for Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, and STEC in symptomatic hosts (strong, low). Specifically,
    1. 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.
    2. 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.
  4. 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 (eg, 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 (strong, moderate).
  5. 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 (strong, moderate). 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 (strong, moderate).
  6. Diagnostic testing is not recommended in most cases of uncomplicated traveler’s diarrhea unless treatment is indicated. Travelers with diarrhea lasting 14 days or longer should be evaluated for intestinal parasitic infections (strong, moderate). 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 postinfectious irritable bowel syndrome (IBS) should be considered for evaluation (strong, moderate).
  7. Clinical consideration should be included in the interpretation of results of multiple-pathogen nucleic acid amplification tests because these assays detect DNA and not necessarily viable organisms (strong, low).
  8. All specimens that test positive for bacterial pathogens by culture-independent diagnostic testing 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 (strong, low). Also, a culture may be required in situations where antimicrobial susceptibility testing results would affect care or public health responses (strong, low).
  9. Specimens from people involved in an outbreak of enteric disease should be tested for enteric pathogens per public health department guidance (strong, low).

V. Which diagnostic tests should be performed when enteric fever or bacteremia is suspected?

  1. 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 (strong, moderate). 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 (weak, moderate). Serologic tests should not be used to diagnose enteric fever (strong, moderate).

VI. When should testing be performed for Clostridium difficile?

  1. Testing may be considered for C. difficile in people >2 years of age who have a history of diarrhea following antimicrobial use and in people with healthcare-associated diarrhea (weak, high). Testing for C. difficile may be considered in people who have persistent diarrhea without an etiology and without recognized risk factors (weak, low). A single diarrheal stool specimen is recommended for detection of toxin or a toxigenic C. difficile strain (eg, nucleic acid amplification testing) (strong, low). Multiple specimens do not increase yield.

VII. What is the optimal specimen (eg, stool, rectal swab, blood) for maximum yield of bacterial, viral, and protozoal organisms (for culture, immunoassay, and molecular testing)? (Table 5)

  1. The optimal specimen for laboratory diagnosis of infectious diarrhea is a diarrheal stool sample (ie, 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 (weak, low). 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 (weak, low).

VIII. What is the clinical relevance of fecal leukocytes or lactoferrin or calprotectin in a person with acute diarrhea?

  1. Fecal leukocyte examination and stool lactoferrin detection should not be used to establish the cause of acute infectious diarrhea (strong, moderate). There are insufficient data available to make a recommendation on the value of fecal calprotectin measurement in people with acute infectious diarrhea.

IX. In which clinical scenarios should nonmicrobiologic diagnostic tests be performed (eg, imaging, chemistries, complete blood count, and serology)?

  1. Serologic tests are not recommended to establish an etiology of infectious diarrhea or enteric fever (strong, low), but may be considered for people with postdiarrheal HUS in which a stool culture did not yield a Shiga toxin–producing organism (weak, low).
  2. A peripheral white blood cell count and differential and serologic assays should not be performed to establish an etiology of diarrhea (strong, low), but may be useful clinically (weak, low).
  3. 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) (strong, high). Examining a peripheral blood smear for the presence of red blood cell fragments is necessary when HUS is suspected (strong, high).
  4. 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 (strong, low). Duodenal aspirate may be considered in select people for diagnosis of suspected Giardia, Strongyloides, Cystoisospora, or microsporidia infection (weak, low).
  5. Imaging (eg, ultrasonography, computed tomography, or magnetic resonance imaging) may be considered to detect aortitis, mycotic aneurysms, signs and symptoms of peritonitis, intra-abdominal free air, toxic megacolon, or extravascular foci of infection in older people with invasive Salmonella 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 (weak, low).

X. What follow-up evaluations of stool specimens and nonstool tests should be performed in people with laboratory-confirmed pathogen-specific diarrhea who improve or respond to treatment, and in people who fail to improve or who have persistent diarrhea?

  1. Follow-up testing is not recommended in most people for case management following resolution of diarrhea (strong, moderate). Collection and analysis of serial stool specimens using culture-dependent methods for Salmonella enterica subspecies enterica serovar Typhi or Salmonella enterica subspecies enterica serovar Paratyphi, STEC, Shigella, nontyphoidal 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 (strong, moderate). Practitioners should collaborate with local public health authorities to adhere to policies regarding return to settings in which transmission is a consideration (strong, high).
  2. A clinical and laboratory reevaluation 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 (weak, low).
  3. Noninfectious conditions, including IBD and IBS, should be considered as underlying etiologies in people with symptoms lasting 14 or more days and unidentified sources (strong, moderate).
  4. Reassessment of fluid and electrolyte balance, nutritional status, and optimal dose and duration of antimicrobial therapy is recommended in people with persistent symptoms (strong, high).

Empiric Management of Infectious Diarrhea

XI. When is empiric antibacterial treatment indicated for children and adults with bloody diarrhea and, if indicated, with what agent?

  1. What are modifying conditions that would support antimicrobial treatment of children and adults with bloody diarrhea?
  2. In which instances should contacts be treated empirically if the agent is unknown?
  1. In immunocompetent children and adults, empiric antimicrobial therapy for bloody diarrhea while waiting for results of investigations is not recommended (strong, low), except for the following:
    1. Infants <3 months of age with suspicion of a bacterial etiology.
    2. 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.
    3. People who have recently travelled internationally with body temperatures ≥38.5°C and/or signs of sepsis (weak, low). See https://wwwnc.cdc.gov/travel/yellowbook/2016/the-pre-travel-consultation/travelers-diarrhea.
  2. 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 (strong, moderate). 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 (strong, moderate).
  3. Empiric antibacterial treatment should be considered in immunocompromised people with severe illness and bloody diarrhea (strong, low).
  4. 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 (strong, moderate).
  5. 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 (strong, low). Antimicrobial therapy should be narrowed when antimicrobial susceptibility testing results become available (strong, high). 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 (weak, low).
  6. 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 (strong, moderate). 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 (strong, low).

XII. When is empiric treatment indicated for children and adults with acute, prolonged, or persistent watery diarrhea and, if indicated, with what agent?

  1. What are modifying conditions that would support empiric antimicrobial treatment of children and adults with watery diarrhea?
  2. In which instances, if any, should contacts be treated empirically if the agent is unknown?
  1. In most people with acute watery diarrhea and without recent international travel, empiric antimicrobial therapy is not recommended (strong, low). 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 lasting 14 days or more (strong, low).
  2. 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 (strong, moderate).

Directed Management of Infectious Diarrhea

XIII. How should treatment be modified when a clinically plausible organism is identified from a diagnostic test?

  1. Antimicrobial treatment should be modified or discontinued when a clinically plausible organism is identified (strong, high).

Supportive Treatment

XIV. How should rehydration therapy be administered?

  1. 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 (strong, moderate), and in people with mild to moderate dehydration associated with vomiting or severe diarrhea.
  2. 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 (weak, low).
  3. 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 (strong, high) or ileus (strong, moderate). In people with ketonemia, an initial course of intravenous hydration may be needed to enable tolerance of oral rehydration (weak, low).
  4. In severe dehydration, intravenous rehydration should be continued until pulse, perfusion, and mental status normalize and the patient awakens, has no risk factors for aspiration, and has no evidence of ileus (strong, low). The remaining deficit can be replaced by using ORS (weak, low). Infants, children, and adults with mild to moderate dehydration should receive ORS until clinical dehydration is corrected (strong, low).
  5. 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 (strong, low).

XV. When should feeding be initiated following rehydration?

  1. Human milk feeding should be continued in infants and children throughout the diarrheal episode (strong, low).
  2. Resumption of an age-appropriate usual diet is recommended during or immediately after the rehydration process is completed (strong, low).

Ancillary Management

XVI. What options are available for symptomatic relief, and when should they be offered?

  1. 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 (weak, low).
  2. Antimotility drugs (eg, loperamide) should not be given to children <18 years of age with acute diarrhea (strong, moderate). Loperamide may be given to immunocompetent adults with acute watery diarrhea (weak, moderate), but should be avoided at any age in suspected or proven cases where toxic megacolon may result in inflammatory diarrhea or diarrhea with fever (strong, low).
  3. Antinausea and antiemetic (eg, ondansetron) may be given to facilitate tolerance of oral rehydration in children >4 years of age and in adolescents with acute gastroenteritis associated with vomiting (weak, moderate).

XVII. What is the role of a probiotic or zinc in treatment or prevention of infectious diarrhea in children and adults?

  1. Probiotic preparations may be offered to reduce the symptom severity and duration in immunocompetent adults and children with infectious or antimicrobial-associated diarrhea (weak, moderate). Specific recommendations regarding selection of probiotic organism(s), route of delivery, and dosage may be found through literature searches of studies and through guidance from manufacturers.
  2. 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 (strong, moderate).

XVIII. Which asymptomatic people with an identified bacterial organism from stool culture or molecular testing should be treated with an antimicrobial agent?

  1. Asymptomatic people who practice hand hygiene and live and work in low-risk settings (do not provide healthcare or child or elderly adult care and are not food service employees) do not need treatment, except asymptomatic people with Salmonella enterica subspecies enterica serovar Typhi in their stool who may be treated empirically to reduce potential for transmission (weak, low). Asymptomatic people who practice hand hygiene and live and work in high-risk settings (provide healthcare or child or elderly adult care and are food service employees) should be treated according to local public health guidance (strong, high).

Prevention

XIX. What strategies, including public health measures, are beneficial in preventing transmission of pathogens associated with infectious diarrhea?

  1. 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 (strong, moderate).
  2. 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 (strong, high). 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 (strong, low). See https://www.cdc.gov/hicpac/2007IP/2007isolationPrecautions.html.
  3. 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 (strong, moderate).
  4. Healthcare providers should direct educational efforts toward all people with diarrhea, but particularly to people with primary and secondary immune deficiencies, pregnant women, parents of young children, and the elderly as they have increased risk of complications from diarrheal disease (strong, low).
  5. Ill people with diarrhea should avoid swimming, water-related activities, and sexual contact with other people when symptomatic while adhering to meticulous hand hygiene (strong, low).

XX. What are the relative efficacies and effectiveness of vaccines (rotavirus, typhoid, and cholera) to reduce and prevent transmission of pathogens associated with infectious diarrhea, and when should they be used?

  1. Rotavirus vaccine should be administered to all infants without a known contraindication (strong, high).
  2. 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 Salmonella enterica subspecies enterica serovar Typhi, people with intimate exposure (eg, household contact) to a documented Salmonella enterica subspecies enterica serovar Typhi chronic carrier, and microbiologists and other laboratory personnel routinely exposed to cultures of Salmonella enterica subspecies enterica serovar Typhi (strong, high). Booster doses are recommended for people who remain at risk (strong, high).
  3. 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 (strong, high). See https://www.cdc.gov/cholera/vaccines.html.

XXI. How does reporting of nationally notifiable organisms identified from stool specimens impact the control and prevention of diarrheal disease in the United States?

  1. 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 (eg, Salmonella, STEC, Shigella, and Listeria) to ensure that control and prevention practices may be implemented (strong, high).

Introduction and Background

The greatest load of infectious diarrhea occurs in low- and middle-income countries, where inadequate sanitation and hygiene are prevailing. Nonetheless, economic development besides creates opportunities for presentation and transmission of enteric pathogens, including ball-shaped travel, food importations, batch output and distribution of food, municipal water systems serving bombastic segments of the population, and widespread manipulation of childcare, long-run care, and amateur water facilities. early risk factors include hospitalization, animal exposures ( specially in public venues ), and certain intimate practices ( Figure 1 ). Outbreaks attributed to contaminated food and urine and contact with infect people and animals continue to occur. Challenge studies involving adult volunteers and epidemiologic studies including those in child concern centers show that infections with Cryptosporidium, Entamoeba histolytica, Giardia, norovirus, rotavirus, Shiga toxin–producing E. coli ( STEC ), and Shigella are spread by abject inoculant, and result in secondary transmission. As a consequence, a considerable load of diarrheal disease occurs in the United States due to a wide kind of endemic and outbreak-associated infections with intestinal pathogens that are adequate to of causing acuate and haunting infectious diarrhea in infants, children, adolescents, and adults, sometimes complicated by extraintestinal manifestations .
The widening array of recognized enteric pathogens, known epidemiologic hazard factors frequently associated with specific pathogens ( table 2 ), increasing number of immunosuppressed people in the United States, increasing total and handiness of diagnostic methods ( board 5 ), increasing numbers of isolates resistant to disinfectant agents, risk of severe illness including hemolytic azotemic syndrome ( HUS ) ascribable to STEC and Guillain-Barré syndrome following Campylobacter infection, and enhanced demand for price containment sharpen the want for evidence-based clinical and public health guidelines. With the growing handiness of multiplex diagnostic panels that can simultaneously detect several intestinal pathogens, clinicians can expect to see patients from whom > 1 pathogen is detected [ 9 ], potentially making excerpt of therapy with allow antimicrobial agents unmanageable. Research is needed to help interpret the clinical meaning of such findings .
These guidelines will focus on the clinical presentation of acute and dogged diarrhea, with stress on infectious etiologies in the industrialize populace, specifically the United States, where diagnostic services are widespread, public health systems are in stead, and endemic cholera and typhoid fever have hanker been controlled. For the approach to diagnosis and management of diarrheal illness in resource-challenged settings, refer to the guidelines published by the World Health Organization ( WHO ) [ 10 ]. It is important to note that at the time that this road map was published, the Clostridium difficile guidelines were still in growth and, while every feat was made to ensure that the recommendations were accordant, there may be minor differences .

Disease Burden and Clinical Presentations

The WHO defines diarrhea as passage of 3 or more free or fluid stools per 24 hours, or more frequently than is normal for an individual person [ 10 ]. patronize exceed of form stools is not diarrhea, nor is passing of loose, “ pasty ” stools by infants consuming human milk .
several clinical presentations of infectious diarrhea have been described, each of which has unlike, albeit overlapping, etiologies, treatments, and outcomes :

  1. Acute watery diarrhea (includes cholera) and acute bloody diarrhea (includes dysentery, which manifests as frequent scant stools with blood and mucus) that lasts <7 days [11]. Acute vomiting and/or diarrhea, often referred to as acute gastroenteritis, is a frequent cause of outpatient visits and hospitalizations in the United States.
  2. Prolonged diarrhea that lasts 7–13 days.
  3. Persistent diarrhea that lasts 14–29 days.
  4. Chronic diarrhea that lasts 30 days or longer.

Acute gastroenteritis is a patronize causal agent of outpatient visits and hospitalizations in the United States, with an estimate annual burden of 179 million outpatient visits, about 500000 hospitalizations, and > 5000 deaths [ 12 ]. Specific data on acute gastroenteritis in adults are sparse, with 1.5 % of all hospital discharges coded as gastroenteritis. The life risk of being discharged from the hospital with a diagnosis of gastroenteritis is estimated to be 1 in 8 among adults in the United States [ 13 ]. The estimate prevalence of diarrhea among adults the month before interview was 3 % –7 % with the rate being age-dependent [ 14 ]. Disease incidence is highest among children < 5 years ; however, the percentages of hospitalization and death are highest in persons 65 years or older [ 15 ] . The Foodborne Diseases Active Surveillance Network ( FoodNet ) national surveillance system maintained by Centers for Disease Control and Prevention ( CDC ) is possibly the most comprehensive source of data on the pathogen-specific burden of diarrheal disease in the United States. Norovirus and Salmonella enterica subspecies were the lead pathogens among the 24 gastroenteritis pathogens ancestral by food that were assessed. Whereas norovirus ( 58 % ) exceeded Salmonella enterica subspecies ( 11 % ) as a cause of illness, Salmonella enterica subspecies exceeded norovirus as a lawsuit of hospitalization ( 35 % v 28 % ) and end ( 28 % vanadium 11 % ). Rotavirus was the most coarse pathogen among children < 5 years before rotavirus vaccine insertion, causing an estimated 3 million annual episodes of acute gastroenteritis, > 500000 outpatient visits and 27000 hospitalizations, and about 25 deaths [ 16–18 ]. Norovirus has assumed the leash since introduction of rotavirus vaccine, and is associated with about 1 million ambulatory care visits and 14000 hospitalizations per annum [ 19, 20 ]. The most common bacterial pathogens in this senesce group are Salmonella enterica subspecies ( 42 % ), Campylobacter ( 28 % ), Shigella ( 21 % ), Yersinia ( 5 % ), and E. coli O157 ( 3 % ) [ 20 ]. in concert these 5 pathogens caused an calculate 291000 illnesses, 103000 doctor visits, 7800 hospitalizations, and 64 deaths annual. Before presentation of rotavirus vaccine, an average of 369 children aged < 5 years died from diarrhea each year ; among infants, the risk of death was increased among african Americans and those with prematureness, low birth weight, less maternal department of education, and gloomy income [ 21 ] . Most acute accent diarrhea episodes in previously goodly, immunocompetent people are of inadequate duration and self-resolving, and are of viral or strange etiology. therefore, testing ground investigation by and large is not warranted. however, many factors may justify the expense and complexity of lab testing including epidemiologic ( table 2 ) and clinical features ( table 3 ), which encompass diarrhea in immunocompromised people, noninfectious and extraintestinal manifestations associated with enteric pathogens ( mesa 4 ), the likely for results of testing ground investigation to impact management, and intuition of an outbreak position . The charge of acute gastroenteritis has been reduced since implementation of 2 US Food and Drug Administration ( FDA ) –licensed rotavirus vaccines, recommended by the Advisory Committee on Immunization Practices ( ACIP ) in 2006 and 2008 [ 22 ]. Clinically significant disease and hospitalization and office visits have been decreased in infants who have received a rotavirus vaccine ( direct security ) vitamin a well as in adults through community protective covering of unvaccinated infants and age-ineligible children and adults [ 23, 24 ] ( indirect, or residential district security ) living in high- and middle-income countries and reductions in all-cause diarrhea deaths in respective middle-income countries . reduction of acute infectious diarrhea besides can be achieved through general measures, including habit of handwriting hygiene ; proper food preparation and storage ; avoidance of bad foods such as undercooked meat and seafood, unpasteurized milk, and soft cheese made with unpasteurized milk ; avoidance of insecure water ; use of infection prevention and see measures in hospitals, childcare, and nursing home settings ; appropriate use of antimicrobial agents ; and appropriate pet survival and supervision of contact with animals, specifically in public settings. In summation, people with diarrhea should refrain from amateur water activities, food homework or avail, and intimate activities while symptomatic. specific hindrance measures, in addition to routine practice of rotavirus vaccine in infants [ 25 ], include typhoid and cholera vaccines for travelers when indicated [ 26 ] . highly effective measures are available to prevent and treat diarrheal disease and its complications. Avoiding dehydration by ensuring adequate fluid and electrolyte inhalation for refilling and maintenance is the anchor of diarrheal illness management. Increasing immunity to disinfectant agents and gamble of worsening illness ( such as diarrhea associated with C. difficile ) can result from disinfectant and antimotility drug use and highlight the need for allow use of these interventions .

SEE ALSO  แท่นยืนคลายเส้น เก้าอี้มหัศจรรย์ คุณตาแสวง บุญชัยเดช โดยโรงงาน ต้นตำรับ ผลิตภัณฑ์ไม้/อุปกรณ์กัวซา

Methodology

Panel Composition

A gore of multidisciplinary experts in management of infectious diarrhea in children and adults was convened in 2012. The control panel consisted of pediatricians and internists with expertness in clinical medicine, infectious disease, epidemiology, gastroenterology, preventive medicine, nutrition, microbiology, and intestinal disease. Panel participants included representatives from the Society for Healthcare Epidemiology of America ( SHEA ), CDC, and the IDSA Standards and Practice Guidelines Committee ( SPGC ). The road map was reviewed and endorsed by SHEA and the Pediatric Infectious Diseases Society. The guidepost was besides reviewed and approved by the IDSA SPGC and the Board of Directors .

Grading of Recommendations Assessment, Development and Evaluation Approach and Process Overview

The gore applied GRADE to the appraisal of quality of evidence and exploitation of recommendations [ 3–7 ]. The timbre of evidence is categorized arsenic high, moderate, low, or very gloomy ; the strength of recommendation is categorized as strong or weak ( Figure 2 ). key factors that determine the persuasiveness of recommendation include choice of evidence, balance between desirable and undesirable effects, and values and preferences. Teleconferences and face-to-face meetings were held in which a list of 21 clinical questions to be addressed in the guidelines was generated, discussed, and prioritized .

Literature Review, Analysis, and Selection

The panel identified stream and valid studies from both the Medline and Embase databases, with a focus on randomized controlled trials ( RCTs ), allowing for admission of systematic reviews and extant exercise guidelines if adequate RCTs and method acting establishment studies for diagnostics did not exist. The search menstruation included 1 January 2000–31 December 2013. Data published after 1 January 2014 besides were considered in the final preparation of the manuscript. The search was restricted to English-language articles and largely was confined to US and/or north american sources. English-language studies with european authors besides were included for the purpose of determining diagnostic guidelines. For international travel–associated infections, such as intestinal fever and cholera, geographic restrictions were not applied. Selected references with relevant updates to rehearse were included .
Following removal of duplicate and irrelevant studies, the empanel based judgments regarding inclusion in the guidelines on evidence demonstrated by the aggregate RCTs and/or the intensity of attest indicated in a taxonomic review of multiple studies. Articles were evaluated for relevance to each of the concentrate sections in the guidelines, up to and including : background ; clinical presentations ; diagnostics ; discussion of nonresponders and continuity ; management ( specific treatment, supportive treatment, empirical discussion, accessory discussion ) ; epidemiology and surveillance ; prevention ; and future treatments. Primary key search terms were as follows : acuate gastroenteritis, antimotility agents, antimicrobial agents, antiparasitic agents, cholera, C. difficile, colitis, diarrhea/dehydration, dysentery, intestinal fever, enteric pathogens, enterocolitis, enzyme immunoassay, gastroenteritis, hand hygiene, management, molecular diagnostics, pseudomembranous enterocolitis, probiotics, rehydration, rotavirus, and STEC .

Guideline and Conflicts of Interest

All panel members complied with IDSA policy on battle of interests, which requires disclosure of any fiscal or early interest that might be construed as constituting an actual, likely, or apparent conflict. Members were provided IDSA ’ s conflicts of pastime disclosure argument and asked to identify associations with companies developing products that might be affected by proclamation of the road map. information was requested regarding use, consultancies, banal possession, honorarium, inquiry fund, expert testimony, talk engagements, and membership on company advisory committees. Decisions were made on a individual footing as to whether an individual ’ mho role should be limited as a result of a conflict. potential conflicts of interest are listed in the Notes section .

Future Revision Dates

At annual intervals, the control panel chair, SPGC affair adviser, and SPGC chair will determine the want for guideline revisions by reviewing current literature. If necessity, the integral gore will be reconvened. When allow, the empanel will recommend revisions to the IDSA SPGC, Board of Directors, and other collaborate organizations for recapitulation and blessing .

Full Recommendations for the Diagnosis and Management of Infectious Diarrhea

Clinical, Demographic, and Epidemiologic Features

I. In people with diarrhea, which clinical, demographic, or epidemiologic features have diagnostic or management implications? (Tables 2–4)

Recommendations
  1. 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 (strong, moderate) (Figure 1).
  2. People with diarrhea who attend or work in child care centers, long-term care facilities, patient care, food service, or recreational water venues (eg, pools and lakes) should follow jurisdictional recommendations for outbreak reporting and infection control (strong, high).
Evidence Summary

A broad image of exposures or conditions have been implicated as sources of infections with specific pathogens ( table 2 ). Exposures or conditions that may suggest certain causes of infectious diarrhea include pulmonary tuberculosis of mollusk, raw milk, unpasteurized juice, undercooked meats, fish, or eggs, or contaminated fruits or vegetables ; exposure to contaminated toast or recreational water ; contact with animals or their feces or environment ; recent disinfectant therapy ; external travel ; institutional exposure ; and anal or oral sexual touch [ 27–47 ] .
Of great importance are exposures associated with food. In a revue of outbreaks of foodborne illness investigated by FoodNet between 2003 and 2008 [ 48 ], a specific food vehicle was identified in 232 of 1200 ( 32 % ) outbreaks [ 49 ]. Outbreaks were most normally reported to be associated with commercial food planning ; this is probable to reflect that outbreaks associated with a unmarried restaurant or other institution may be more likely than early outbreaks to be noticed, reported to populace health officials, and investigated. early crucial exposures implicated in outbreaks include animal reach [ 41, 50, 51 ], amateur water exposure [ 52 ], and sexual practices [ 53 ] ( Table 2 ) .
Outbreaks of diarrhea in institutional settings are a substantial populace health problem. The National Outbreak Reporting System [ 54 ] collects data on waterborne and foodborne disease outbreaks, one-on-one transmitted disease outbreaks, animal contact disease outbreak, environmental contaminant disease outbreaks, and other intestinal illness outbreaks. During 2009–2013, the National Outbreak Reporting System reported 10756 acute gastroenteritis outbreaks for which the primary mode of infection occurred through one-on-one contact, environmental contaminant, and strange modes of transmittance. These outbreaks resulted in 356530 report illnesses, 5394 hospitalizations, and 459 deaths. In 7001 outbreaks where a typeset was reported, 70 % occurred in long-run concern facilities. In contrast, 59 % of Shigella-associated outbreaks and 36 % of Salmonella-associated outbreaks were identified in childcare facilities. Norovirus was implicated in 84 % of 2430 outbreaks where an etiology was suspected or confirmed ; bacterial pathogens were identified in a solid minority [ 55 ]. During 2009–2013, norovirus accounted for most deaths and healthcare visits associated with acute gastroenteritis outbreaks. specific infection control guidelines are recommended for control of norovirus and the extremely chlorine-tolerant Cryptosporidium in institutional settings [ 56, 57 ]. Food actor health or hygiene has been identified as a contributing divisor in 64 % of foodborne outbreaks associated with restaurants in the United States [ 58 ] .

II. In people with fever or bloody diarrhea, which clinical, demographic, or epidemiologic features have diagnostic or management implications? (Tables 1–3)

Recommendations
  1. People with fever or bloody diarrhea should be evaluated for enteropathogens for which antimicrobial agents may confer clinical benefit, including Salmonella enterica subspecies, Shigella, and Campylobacter (strong, low).
  2. 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 had consumed foods prepared by people with recent endemic exposure, or has laboratory exposure to Salmonella enterica subspecies enterica serovar Typhi and Salmonella enterica subspecies enterica serovar Paratyphi (strong, moderate). In this document, Salmonella Typhi represents the more formal and detailed name Salmonella enterica subspecies enterica serovar Typhi, and Salmonella Paratyphi corresponds to the Paratyphi serovar.
Evidence Summary

Although bacterial causes of diarrhea can have similar clinical presentations, they differ with respect to clinical management. For example, whereas disinfectant agents may be indicated for Campylobacter or Shigella infections, they are not indicated for STEC or for most salmonella infections .
identification of bacterial agents can prevent other unnecessary procedures such as colonoscopy, abdominal surgery, or checkup discussion for suspect ulcerative colitis. conversely, negative fecal matter studies for infectious pathogens increase misgiving for noninfectious conditions such as inflammatory intestine disease ( IBD ) .
Salmonella enterica serovar Typhi and Paratyphi A and Paratyphi B campaign bacteremic illnesses referred to respectively as typhoid and paratyphoid fever, and jointly as enteric fever. These conditions are characterized by fever that may be associated with headache, inanition, malaise, and abdominal pain, followed by hepatosplenomegaly and daze. While the portal vein of entrance is the gastrointestinal tract, diarrhea is an uncommon feature [ 59 ] .
Typhoid fever incidence is high in parts of South and Southeast Asia, and moderate in Central and South America, Africa, Central and East Asia, and Oceania [ 60 ]. Typhoid fever outbreaks in the United States are rare and normally associated with foodborne transmittance from an asymptomatic aircraft carrier [ 61 ]. FoodNet datum from the period 2004–2009 demonstrated that a history of travel was reported in 68 % of patients with Salmonella enterica serovar Typhi and 50 % of patients with Salmonella enterica serovar Paratyphi [ 35 ]. Typhoid fever may be unmanageable to distinguish from early febrile conditions in render travelers, and can present with fever without focus, abdominal trouble without diarrhea, or with extraintestinal focus of contagion [ 62 ] .

III. What clinical, demographic, or epidemiologic features are associated with complications or severe disease? (Tables 2 and 3)

Recommendations
  1. 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 (strong, high).
  2. 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 (strong, moderate). If available, diagnostic approaches that can distinguish between Shiga toxin 1 and Shiga toxin 2, which is typically more potent, could be used (weak, moderate). 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 (strong, moderate).
  3. Clinicians should evaluate people for postinfectious and extraintestinal manifestations associated with enteric infections (strong, moderate) [8].
Evidence Summary

book depletion is a frequently identified risk gene for diarrhea-related deaths in people of all ages in the United States ; early related risk factors include fluid and electrolyte disorders, nontraumatic shock, and acute nephritic failure [ 63, 64 ]. In addition, dehydration at the time of admission among children with postdiarrheal HUS is associated with an increased need for dialysis [ 65 ]. Intravenous fluid administered during the diarrhea phase of STEC infections reduces the hazard of oligoanuric nephritic bankruptcy among those children who subsequently develop HUS [ 66 ] .
Although most patients with laboratory-confirmed STEC who develop HUS have bloody diarrhea, approximately 10 % do not [ 67 ]. In addition to patient reported bloody diarrhea or visibly bally stool, other factors independently associated with increase risk of STEC O157 infection compared with other intestinal infections in patients of all ages include abdominal tenderness and absence of fever at first checkup evaluation [ 68 ]. approximately 65 % of patients infected with E. coli O157 will have a peripheral white lineage cell count > 10000 cells/µL [ 69 ]. early identification of STEC infections is significant to reduce the gamble of complications and the risk of one-on-one transmission. It is authoritative to perform both cultures for STEC O157 and screen for Shiga toxin ( either in broth cultures, not stool ) or the genes that encode this toxin kin, because STEC O157 is the most systematically virulent STEC in the United States, and early on recognition through culture can aid in clinical management and public health dominance measures. Detection of all early STEC serotypes first requires detection of Shiga toxin ( or the genes that encode them ) [ 70 ] .
STEC carrying Shiga toxin 2 ( stx2 ) genes are associated with increase risk of both bally diarrhea and HUS [ 71, 72 ]. In the United States, most STEC stains isolated from patients with HUS are serogroup O157, and are stx2 cocksure. New manifold nucleic acid amplification tests ( MP-NAATs ) that can detect tell of multiple pathogens and toxins can distinguish between Shiga toxins 1 and 2 and some assays besides distinguish E. coli O157. Although clinical laboratories can not typically differentiate between subtypes of Shiga toxin 2, subtypes 2a, 2c, and 2d are associated with more austere disease [ 73 ]. Known postinfectious manifestations of infections with their associated intestinal organisms are listed in mesa 4. When a clinical syndrome consistent with one of these manifestations is encountered, an exposure history should be obtained along with a diagnostic evaluation and directed management, which may have public health or outbreak evaluation implications. early identification of peculiarly deadly STEC infection ( eg, STEC O157 and other Shiga toxin 2–producing strains ) facilitates rapid implementation of measures in the home that prevent cross-contamination [ 74 ] .

Diagnostics

IV. Which pathogens should be considered in people presenting with diarrheal illnesses, and which diagnostic tests will aid in organism identification or outbreak investigation?

Recommendations
  1. 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 (strong, moderate). 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 (strong, low). 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 (strong, moderate).
  2. 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, people with 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 (strong, moderate).
  3. Stool testing should be performed under clearly identified circumstances (Table 2) for Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, and STEC in symptomatic hosts (strong, low). Specifically,
    1. 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.
    2. 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.
  4. 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 (eg, 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 (strong, moderate).
  5. 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 (strong, moderate). 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 (strong, moderate).
  6. Diagnostic testing is not recommended in most cases of uncomplicated traveler’s diarrhea unless treatment is indicated. Travelers with diarrhea lasting 14 days or longer should be evaluated for intestinal parasitic infections (strong, moderate). 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 postinfectious irritable bowel syndrome (IBS) should be considered for evaluation (strong, moderate).
  7. Clinical consideration should be included in the interpretation of results of multiple-pathogen nucleic acid amplification tests because these assays detect DNA and not necessarily viable organisms (strong, low).
  8. All specimens that test positive for bacterial pathogens by culture-independent diagnostic testing 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 (strong, low). Also, a culture may be required in situations where antimicrobial susceptibility testing results would affect care or public health responses (strong, low).
  9. Specimens from people involved in an outbreak of enteric disease should be tested for enteric pathogens per public health department guidance (strong, low).
Evidence Summary

determination of the precise lawsuit of diarrhea is not constantly necessary. appraisal of a stool specimen to determine the lawsuit should be performed on patients at high risk of austere illness and for whom identification of a pathogen would be important for the affected role or for public health reasons. As first described in the original IDSA guidelines on management of infectious diarrhea [ 1 ], diagnostic algorithm that combine clinical and epidemiologic factors that fitting requirements of clinical medicate and public health are needed. Although the majority of diarrheal illnesses are self-limited and identification of the infectious etiology frequently has little value to these individual patients, for certain infections, an organism-specific diagnosis is important to guiding clinical management. furthermore, from a public health position, an organism-specific diagnosis is valuable for the majority of diarrheal illnesses because designation of an organism facilitates outbreak signal detection and monitoring of disease trends. selective testing recommendations below are based on clinical management needs angstrom good as on the efficient use of diagnostic testing to meet the needs of public health surveillance systems .
designation of bacterial pathogens can be significant for both clinical management and populace health disease control efforts. however, testing all patients with acuate diarrhea for these pathogens would be inefficient. Among adults presenting with diarrhea to emergency departments in the United States, 17 % of patients who submitted a fecal matter specimen ( as opposed to rectal swab ) were found to have a bacterial intestinal infection. A bacterial etiology was found in 5 % –11 % of children seeking care in emergency departments and outpatient settings [ 75–77 ]. Restricting testing to patients with bloody stools, fever, or abdominal softheartedness can increase the likelihood of identifying a bacterial pathogen [ 68, 76–79 ] ( board 5 ). gamble factors for invasive nontyphoidal Salmonella infection include young and advanced senesce, mar immunity ascribable to human immunodeficiency virus ( HIV ) infection and cytotoxic chemotherapy, malnutrition, hemoglobinopathies, holocene malaria, and cirrhosis [ 80–82 ]. other bacterial infections, including Campylobacter [ 83 ] and Shigella [ 44, 84 ] and Listeria infections are more probably to be hard or perennial in patients with HIV infection. Aneurysms of the aorta and aortitis can occur in aged patients with encroaching nontyphoidal salmonellosis or yersiniosis [ 85, 86 ] .
risk factors for invasive noncholera vibriosis, specially Vibrio vulnificus infections, are chronic liver disease ( including cirrhosis, alcoholic liver disease, and hepatitis ), iron overload states ( hemochromatosis, hemolytic anemia, or chronic nephritic failure ) and other immunocompromising conditions [ 87, 88 ] .
Yersinia enterocolitica can be associated with an align of clinical presentations including, but not limited to, nonbloody diarrhea, bloody diarrhea, and a febrile pseudoappendicular syndrome that can mimic appendicitis. invasive yersiniosis in an pornographic may be associated with the presence of mycotic aneurysms [ 86 ]. Foods that have been associated with Y. enterocolitica infections include pork ( eg, chitterlings ) and dairy products. Higher risk groups in the United States include young african american and asian children, particularly during winter months, vitamin a well as diabetics and those with chronic liver disease, malnutrition, or iron-overload states. The higher rates among african american children had been attributable to cross-contamination within the home during homework of chitterlings, a seasonal worker cup of tea prepared from pig bed intestines. however, the high incidence rates in african american children observed in the late 1990s have declined dramatically following contraceptive health campaigns focusing on avoidance of cross-contamination in the kitchen [ 89 ] .
recognition and probe of outbreaks together serve authoritative roles in reducing the effect of diarrheal illnesses by truncating the duration of the outbreak and uncovering the put up factors that led to the outbreak so that those factors can be addressed to prevent future outbreaks and illnesses. An organism-specific diagnosis normally is necessary for public health control efforts, because clinical factors alone rarely are sufficient to distinguish between etiological agents. Identifying the etiological agent ( s ) from ill people is important for case determine and investigating possible sources of infection. The most coarse causal agent of diarrheal disease outbreaks is norovirus, but a broad range of bacterial and parasitic agents have been implicated in outbreaks [ 90–94 ]. The specific pathogens for which to test may vary by clinical presentation and exposures. Health departments can provide guidance on testing, and much populace health laboratories can assist in testing for agents that exceed the diagnostic capacity of the clinical lab .
Immunocompromised people are more probable to experience hard or elongated illness. Diarrhea in immunocompromised patients may involve a broad spectrum of potential causes, including bacterial, viral, parasitic, and fungal pathogens depending on underlying immune status [ 95 ]. In addition, people with HIV-associated immune compromise are at risk for diarrhea due to enteroaggregative E. coli [ 96–98 ], Cryptosporidium [ 99 ], microsporidia [ 100–102 ], Cystoisospora belli ( once Isospora belli ), CMV, and Mycobacterium avium complex ( MAC ) [ 95, 103 ]. Besides stool examination, other investigations may be necessary for the HIV-infected affected role, including blood cultures for diagnosis of MAC infection and colonoscopy with biopsy for CMV enteritis. Diarrhea caused by some protozoa ( eg, Cryptosporidium, Cyclospora, Cystoisospora ) or microsporidia is more likely to be severe, chronic, or relapsing in immunocompromised people, particularly those with impair cell-mediated exemption, including promote HIV infection [ 104 ]. Because microscopic examination of toilet for ovum and parasites is improbable to include testing for Cryptosporidium and Cyclospora, clinicians should specifically request Cryptosporidium and/or Cyclospora testing. noninfectious etiologies including adverse effects of antiretroviral therapy or chemotherapy besides may account for dogged diarrhea in immunocompromised hosts. In some patients with diarrhea lasting ≥30 days, testing for HIV may be appropriate [ 105 ] .
Chronic and severe norovirus infection has been reported in patients receiving immunosuppression following harmonium transplant [ 106 ]. Patients who acquire norovirus infection while hospitalized, specially people with immunocompromising conditions and people of promote age, may be more likely to die. Guidelines for prevention and control of norovirus gastroenteritis outbreaks in healthcare settings have been published [ 56 ]. People > 90 years of age residing in long-run worry facilities have a 20 % –30 % increased gamble of death and hospitalization during norovirus outbreaks [ 107 ]. however, diagnosis of norovirus infections largely has been limited to infections occurring as part of outbreaks. Localized outbreaks affecting hospital wards and long-run manage facilities may be more likely to be investigated [ 107–109 ]. Investigations to assess the endemic rates of norovirus infection are ongoing. dogged non-vaccine-related and vaccine-related rotavirus diarrhea has been reported in unseasoned children with basal immunodeficiency [ 110, 111 ], but rotavirus disease and hospitalizations overall have been reduced markedly since licensure of the 2 ACIP-recommended rotavirus vaccines [ 112 ] .
The majority of traveler ’ mho diarrhea is self-limited, caused by bacterial and, to a lesser extent, viral pathogens, and lasts for < 7 days. Most TD is self-treatable with oral rehydration therapy, and, for nonbloody diarrhea in adults, an antimotility agent [ 113 ]. approximately 10 % of traveler ’ randomness diarrhea is caused by parasitic infections, which can persist for weeks to months, with giardiasis being the most coarse. Clostridium difficile–associated diarrhea is of increasing concern among travelers with haunting diarrhea, specially travelers with holocene antimicrobial agent therapy, either as self-treatment for traveler ’ s diarrhea or for other indications [ 114, 115 ]. The distribution of gastrointestinal tract pathogens varies well by region of travel. In a US FoodNet study between 2004 and 2009, the majority of cases of typhoid fever, paratyphoid fever, and Shigella dysenteriae infection among others, were associated with travel [ 35 ]. An abnormal D-xylose assimilation test indicates the hypothesis of tropical sprue, which is most park in adults visiting tropical areas for long periods of time . Multipathogen nucleic acerb amplification tests can simultaneously detect viral, parasitic, and bacterial agents, including some pathogens that previously could not be easily detected in the clinical mise en scene such as norovirus, and enterotoxigenic E. coli ( ETEC ), enteropathogenic E. coli ( EPEC ), and enteroaggregative E. coli ( EAEC ) in less clock time than traditional methods. The abruptly prison term to results could reduce inappropriate use of disinfectant agents to treat infections that do not require antimicrobial therapy and could shorten the time to targeted management and isolation measures for certain infections such as STEC O157. With these assays, it is common to detect the bearing of > 1 pathogen that may differ with respect to clinical management [ 116–118 ]. Furthermore, even a plus result for 1 pathogen should be interpreted in the context of the patient ’ s clinical presentation, because less is known about the clinical meaning of tests that detect nucleic acidic as compared with traditional assays that broadly detect feasible organisms. The importance of detection of multiple pathogens in the same specimen is much ill-defined ; it is obscure if all pathogens detected in the specimen are clinically relevant or if one is more powerfully associated with the illness .
rendition of results will improve as more data become available regarding the operation of these assays. For at least one assay, current data testify that harmony with traditional diagnostic methods may vary by pathogen [ 118 ]. Some experts have proposed that these assays may be peculiarly well suited for making an organism-specific diagnosis in immunocompromised patients [ 119 ]. The current FDA-cleared multiplex assays do not quantify the come of nucleic acid present. Development of quantitative assays may aid in rendition of results [ 120 ] .
Guidelines by IDSA and the american Society for Microbiology ( ASM ) on utilization of the clinical microbiology testing ground trace optimum tests for detection of pathogens, including those causing diarrhea [ 121 ]. The complete findings are summarized in board 5. Since publication of those guidelines, several gastrointestinal panels that detect > 20 viral, bacterial, and epenthetic intestinal organisms have become available. The handiness of one of these panels american samoa well as early assays may vary among clinical laboratories, making requisitions singular to the lab to which the sample distribution is submitted.

There are crucial drawbacks to the increasing use of culture-independent diagnostic tests ( CIDTs ), including enzyme immunoassays and NAATs in the clinical mount. First, replacement of culture by CIDT in clinical laboratories will impede outbreak signal detection and investigation. Public health has made important strides in detection, investigate, and controlling outbreaks of enteric illness using molecular subtyping of the infecting bacterial strains in public health laboratories [ 122 ]. The net effect of this enhance surveillance and control has been to prevent thousands of illnesses [ 123 ]. refilling of culture by CIDT without preserving access to isolates will impede detection of disperse outbreaks, and thus reduce the capacity of populace health to control and to prevent them. Second, for the person, CIDTs do not provide information on antimicrobial susceptibility to guide clinical management. Actions are needed to avoid this negative impact on public health. In the short terminus, specimens that test positive for a bacterial pathogen by a CIDT for which isolate submission is requested or required under public health report rules should be cultured, either at the clinical testing ground or at a public health testing ground. Cultured organisms can be sent to populace health laboratories for species designation, serotyping and further subtyping by molecular methods ( eg, pulsed-field gel electrophoresis, and, more recently, whole-genome sequence ). Subtyping enable detection of increases in infections caused by a specific breed and besides facilitates outbreak investigations by increasing the probability that case-patients included in an probe are likely to have had a common exposure. In the longer terminus, culture-independent methods that serve clinical diagnostic needs and are able to provide subtyping information to distinguish strains are needed [ 124–128 ] .

V. Which diagnostic tests should be performed when enteric fever or bacteremia is suspected?

Recommendation
  1. 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 (strong, moderate). 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 (weak, moderate). Serologic tests should not be used to diagnose enteric fever (strong, moderate).
Evidence Summary

For the diagnosis of intestinal fever, aerobic blood culture has a sensitivity of approximately 50 % compared with the more invasive and technically complex learning of bone marrow acculturation [ 129 ]. Bone marrow culture is probable to be more sensitive than blood culture for diagnosis of invasive nontyphoidal Salmonella enterica infection [ 130, 131 ]. Routine aerobic rake culture is recommended as the act hardheaded conventional diagnostic and for the initial diagnostic appraisal in people with suspect intestinal fever or encroaching salmonellosis [ 129–131 ]. In intestinal fever, culture of other samples such as toilet, duodenal fluid, and urine may be helpful. Due to poor performance characteristics, serologic tests should not be used for diagnosis of intestinal fever. Nucleic acid amplification tests lack sensitivity for signal detection of Salmonella enterica serovar Typhi in lineage, but may be utilitarian for rapid detection and identification of Salmonella enterica serovar Typhi in research settings [ 129, 130 ] .
Blood culture should be performed in all people with signs of blood poisoning and when enteric fever is suspected. Blood cultures may be considered in immunocompromised people who are febrile or from whom bacterial pathogens are detected by stool test. Some clinical laboratories are now using blood culture technology that can identify a pathogen without isolation [ 132 ]. In these situations, it is all-important to isolate the organism to facilitate disinfectant susceptibility test and extra molecular characterization by public health laboratories. As the median magnitude of bacteremia in enteric fever and encroaching nontyphoidal Salmonella enterica disease are broken at 0.3 and 1.0 colony-forming units/mL of blood, respectively, larger volumes of rake need to be obtained to maximize detection [ 131 ]. Two to three 20-mL rake cultures are adequate for detection of bacteremia in adults [ 133 ]. Lower volumes may be sufficient for detection in infants and children who have higher magnitudes of bacteremia than adults [ 131 ]. Blood cultures may be drawn simultaneously and should be collected anterior to presidency of antimicrobial agents to maximize sensitivity. continuously monitored blood culture systems may shorten the time to detection and improve sensitivity compared with manual blood culture methods .

SEE ALSO  Sty - Symptoms and causes

VI. When should testing be performed for Clostridium difficile?

Recommendation
  1. Testing may be considered for C. difficile in people >2 years of age who have a history of diarrhea following antimicrobial use and in people with healthcare-associated diarrhea (weak, high). Testing for C. difficile may be considered in people who have persistent diarrhea without an etiology and without recognized risk factors (weak, low). A single diarrheal stool specimen is recommended for detection of toxin or a toxigenic C. difficile strain (eg, nucleic acid amplification testing) (strong, low). Multiple specimens do not increase yield.
Evidence Summary

A complete discussion of Clostridium difficile infection ( CDI ) in adults and children will be addressed in the update IDSA/SHEA guidelines devoted to this subject [ 134 ] .
up to 85 % of patients with C. difficile provide a history of photograph to antimicrobial agents within the former 28 days. Although a wide crop of disinfectant agents has been implicated, the most strongly associated with development of CDI include cephalosporins, β-lactam/β-lactamase inhibitors, clindamycin, and quinolones. however, the persuasiveness of association between antibiotic classes and growth of CDI may be confounded by hospitalization insurance, use of multiple antibiotic classes, and duration of exposure. There is increasing recognition of community-acquired C. difficile ; some strains appear to be genetically distinct from hospital strains .
Children occasionally develop austere C. difficile disease, but this appears to be uncommon, and occurs by and large among older children. Concomitantly with adults, the incidence of infection has increased among hospitalize children, and community-acquired infections with hypervirulent strains have emerged, but the asperity of disease has not increased as it has with adults. In the absence of well-controlled studies that take into account the frequency of asymptomatic colonization, it remains changeable whether these raw epidemiologic patterns represent an emerging burden of disease or an increase pace of asymptomatic colonization among children with comorbidities and exposure to factors that alter the intestinal microbiota such as hospitalization, antibiotics, and immunosuppression. The senior high school frequency ( up to 70 % ) of asymptomatic colonization among healthy newborns is another agent that confounds understand of the epidemiology of CDI in children. These rates gradually fall to pornographic levels as the microbiota of the lower intestine becomes established by about 2 years of age, but however render the significance of identifying the organism or toxin in an individual child < 2 years of age uncertain . clostridium difficile should be considered in patients with diarrhea occurring in hospitals. Studies have found that C. difficile is more prevailing in diarrheal stools obtained > 72 hours after entree. colonization is coarse in hospitalize patients and residents of long-run caution facilities. Because asymptomatic baby buggy is recognized, patients without diarrhea should not be tested or treated. In the testing ground, this is normally implemented using a rejection policy for shape stool .
A act of different testing assays and algorithm combining different assays are available. Though kits that test for toxin A and B appear to demonstrate poor sensitivity compared with C. difficile cytotoxicity assay ( CCA ) or toxigenic acculturation, testify suggests that patients with positive toxigenic culture and positivist CCA have a poorer consequence than those with a negative CCA solution. In the future, when it is potential to reconstruct the genome from specimens without first culturing the isolate, molecular subtype–based epidemiology may help in controlling the diffuse of this organism .

VII. What is the optimal specimen (eg, stool, rectal swab, blood) for maximum yield of bacterial, viral, and protozoal organisms (for culture, immunoassay, and molecular testing)? (Table 5)

Recommendation
  1. The optimal specimen for laboratory diagnosis of infectious diarrhea is a diarrheal stool sample (ie, 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 (weak, low). 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 (weak, low).
Evidence Summary

A diarrheal stool sample distribution provides greater faecal material and is less prone to environmental abasement when compared with a rectal swab. Viral and bacterial infectious agents were more likely to be detected from stool samples ( 49 % of cases in one discipline ) than from rectal swab ( 9 % of cases ) in adults presenting to emergency departments with diarrhea ; detection of norovirus, rotavirus, and bacterial pathogens was 4- to 6-fold greater from stools samples than from rectal swab. For a exhaustive review on how samples should be collected, stored, and transported, see the IDSA/ASM Guide to Utilization of the Microbiology Laboratory [ 121 ] ; the recommendations for infectious diarrhea in these previously published guidelines are summarized in table 5. In general, merely a individual stool specimen is required. however, acculturation of extra specimens may increase the sensitivity to detect bacterial pathogens in patients with haunting diarrhea [ 135 ] .
clinical laboratories that have adopted newer CIDTs may have different specimen requirements. however, evening in these circumstances, collection of a diarrheal stool specimen is important for culture of samples that test incontrovertible by CIDT for bacterial pathogens for public health considerations and disinfectant susceptibility test, until CIDTs that can serve these functions are available in the clinical put [ 128 ] .

VIII. What is the clinical relevance of fecal leukocytes or lactoferrin or calprotectin in a person with acute diarrhea?

Recommendation
  1. Fecal leukocyte examination and stool lactoferrin detection should not be used to establish the cause of acute infectious diarrhea (strong, moderate). There are insufficient data available to make a recommendation on the value of fecal calprotectin measurement in people with acute infectious diarrhea.
Evidence Summary

faecal leukocyte examination may be used to differentiate inflammatory diarrhea from secretory diarrhea, but performs ailing to establish the infectious campaign of diarrhea, particularly among inpatients [ 136 ]. faecal leukocyte morphology degrades in feces during enchant and march, making accurate recognition and quantitation unmanageable. In incendiary diarrhea, faecal leukocytes are intermittently show and unevenly distributed in stool, limiting sensitivity. Lactoferrin has been used as a deputy marker for faecal leukocytes as it is not degraded during transport and serve [ 137 ]. Lactoferrin screen has been proposed as a cost-saving measure to select a subgroup of stool samples with higher pretest probability of being positive for bacterial pathogens by stool acculturation [ 137 ], but is not used normally in stool process algorithm by clinical laboratories. furthermore, lactoferrin besides is present in noninfectious IBD, resulting in decrease specificity for infectious incendiary diarrhea [ 138, 139 ]. Lactoferrin is a normal component of human milk and therefore may be award in varying amounts in stools of infants who consume human milk, making assay results unmanageable to interpret in these infants. Calprotectin is a protein released in big quantities by granulocytes during inflammatory processes. Calprotectin is an build marker of intestinal excitement used in patients with IBD. There are limited and at odds reports about the value of measuring faecal calprotectin levels in patients with acute infectious diarrhea. Whereas some studies in children and adults suggest that higher calprotectin levels may suggest bacterial etiologies of diarrhea [ 140, 141 ], other studies have not found diagnostic value [ 142, 143 ] .

IX. In which clinical scenarios should nonmicrobiologic diagnostic tests be performed (eg, imaging, chemistries, complete blood count, and serology)?

Recommendations
  1. Serologic tests are not recommended to establish an etiology of infectious diarrhea or enteric fever (strong, low), but may be considered for people with postdiarrheal HUS in which a stool culture did not yield a Shiga toxin–producing organism (weak, low).
  2. A peripheral white blood cell count and differential and serologic assays should not be performed to establish an etiology of diarrhea (strong, low), but may be useful clinically (weak, low).
  3. 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) (strong, high). Examining a peripheral blood smear for the presence of red blood cell fragments is necessary when HUS is suspected (strong, high).
  4. 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 (strong, low). Duodenal aspirate may be considered in select people for diagnosis of suspected Giardia, Strongyloides, Cystoisospora, or microsporidia infection (weak, low).
  5. Imaging (eg, ultrasonography, computed tomography, or magnetic resonance imaging) may be considered to detect aortitis, mycotic aneurysms, signs and symptoms of peritonitis, intra-abdominal free air, toxic megacolon, or extravascular foci of infection in older people with invasive Salmonella 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 (weak, low).
Evidence Summary

Although not useful in most circumstances, serologic tests can aid in diagnosing an antecedent STEC infection ( the CDC has validated testing available for serogroups O157 and O111 ) among patients with HUS if a Shiga toxin–producing organism has not been identified by fecal matter culture and Shiga toxin testing [ 67 ]. Due to poor performance characteristics, serologic tests, such as the Widal test, should not be used for diagnosis of enteric fever [ 62 ] .
The sum white blood cellular telephone count and derived function may provide suggestion of a bacterial etiology when viral or epenthetic etiologies besides are being considered. The entire flannel lineage cell count and neutrophil count are frequently increased with invasive bacterial pathogens and the platelet count may be elevated. In situations of bacterial sepsis, the total white lineage cellular telephone reckon and platelet count may be lowered compared with convention values for age. shigellosis can be associated with a leukemoid reaction. A white blood cell count that is within range for age and a lymphocytic predomination may occur with viral etiologies. An increased eosinophil count may occur with parasitic infections that involve a tissue phase. A high sum white blood cell count and neutrophil count much occur in patients with STEC O157 infections who subsequently develop HUS [ 144, 145 ]. Monocyte predomination may suggest the presence of an intracellular pathogen such as Salmonella [ 146 ] .
As HUS evolves over meter, a individual complete rake cell count is not sufficient to define hazard. In fact, a near-normal hemoglobin measure may suggest dehydration. Patients with a decreasing platelet count swerve during days 1–14 of the diarrheal illness are at greater hazard of developing HUS. daily monitor can stop when the platelet count begins to increase or stabilize in patients with answer or resolving symptoms. Patients with an increasing creatinine degree and rake coerce and signs of volume overload should be monitored closely and should receive concern in a center that can manage acute nephritic failure [ 147 ] .
endoscopy with modest intestine biopsy is useful for diagnosis of MAC and microsporidiosis. If colitis is suspected, sigmoidoscopy with biopsy of abnormal mucous membrane may assist in differentiating infectious colitis from incendiary intestine disease, CMV disease, or C. difficile colitis. Abdominal computed imaging may detect mucosal thickening or other changes related to colitis and is helpful when intestinal disease is considered. Proctoscopic interrogation may be useful in diagnosing proctitis in patients who have had receptive anal sexual intercourse. Duodenal aspirate has been shown to be utilitarian in the diagnosis of Giardia and Strongyloides infection in patients with recurring diarrhea in whom stool evaluation did not yield an etiology [ 148, 149 ] .
Although aortitis and aneurysm formation are rare complications of Salmonella and Yersinia diarrhea, they are universally fatal without allow checkup and surgical treatment. Delays in diagnosis have been associated with poor prognosis [ 85, 86 ] .

X. What follow-up evaluations of stool specimens and nonstool tests should be performed in people with laboratory-confirmed pathogen-specific diarrhea who improve or respond to treatment, and in people who fail to improve or who have persistent diarrhea?

Recommendations
  1. Follow-up testing is not recommended in most people for case management following resolution of diarrhea (strong, moderate). Collection and analysis of serial stool specimens using culture-dependent methods for Salmonella enterica subspecies enterica serovar Typhi or Salmonella enterica subspecies enterica serovar Paratyphi, STEC, Shigella, nontyphoidal 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 (strong, moderate). Practitioners should collaborate with local public health authorities to adhere to policies regarding return to settings in which transmission is a consideration (strong, high).
  2. A clinical and laboratory reevaluation 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 (weak, low).
  3. Noninfectious conditions, including IBD and IBS, should be considered as underlying etiologies in people with symptoms lasting 14 or more days and unidentified sources (strong, moderate).
  4. Reassessment of fluid and electrolyte balance, nutritional status, and optimal dose and duration of antimicrobial therapy is recommended in people with persistent symptoms (strong, high).
Evidence Summary

The common duration of symptoms of diarrhea with or without aesculapian therapy can be expected to vary by organism, but duration of up to 10–14 days or longer can occur. persistent carriage is a concern for some etiological agents, such as Salmonella, STEC, and Shigella, and there are public health concerns stemming from prolong passenger car for people working in food serve, child care, group settings, and long-run care facilities. The majority of patients with diarrhea will not have a testing ground diagnosis, so laboratory-based specific recommendations would be of minimal use. Repeat stool cultures are required in certain situations to enable hark back to employment and group social activities ; these requirements may differ by local jurisdiction. When required, repeat testing is best done using traditional culture methods, as CIDTs do not indicate that living organisms are introduce, and have not been validated as desirable for proof of cure .
All patients should be educated about mode of unfold of diarrheal diseases, typically fecal-oral, and warned that they potentially may be infectious to others after symptom resolution and for ensuing weeks to months. careful hand hygiene should be observed, peculiarly if the patient is involved in food readiness, child or adult education, or healthcare. specific situations in which extra follow-up should be considered are listed below .
As jurisdictional and state regulations regarding the number and clock of stool cultures required for return to the child care setting may vary, clinicians are advised to consult their local public health authority for guidance. As an example, 3 minus stool cultures obtained at least 24 hours aside, at least 48 hours after cessation of disinfectant therapy, and not earlier than 1 month after symptom attack may be required for readmission of children and staff with Salmonella serovar Typhi infection. If any fecal matter acculturation yields Salmonella Typhi, obtain monthly stool cultures during the subsequent 12 months until at least 3 consecutive stool cultures are without growth of Salmonella Typhi. negative stool culture results typically are not required for return to childcare settings in children or staff with nontyphoidal Salmonella enterica serovar infections. For STEC, children are excluded from child caution until diarrhea resolves, and 2 stool cultures negative for the organism typically are required for readmission [ 150 ]. Given the increasing detection of non-O157 STEC infections in recent years, some jurisdictions have begun basing exclusion policies of people with STEC on the observe virulence of the illness and virulence gene profile of the infect strain. regular and coherent follow-up of patients recovering from diarrhea-associated HUS is recommended until testing ground and clinical parameters have returned to normal values. Parameters of concern include indicators of nephritic serve, anemia, and thrombocytopenia. There is no consensus for the frequency of follow-up lab testing beyond the point that clinical and lab resolution is achieved .
In the site where a pathogen has not been identified, it may be fair to reevaluate toilet and/or blood if there is tell of systemic symptoms, for evaluation for a previously undetected pathogen .
If clinical symptoms worsen, there are several possible explanations. If an disinfectant agent has been given, antibiotic-associated diarrhea ( non–C. difficile ) should be considered. If the patient is hospitalized or has had healthcare vulnerability, C. difficile becomes an extra circumstance, particularly if there is fever or leukocytosis > 20000 cells/μL [ 151 ], and stool should be assessed for C. difficile toxin or a toxigenic C. difficile strain ( eg, NAAT ). Stool besides should be submitted for culture and susceptibility to determine the presence of a bacterial etiology. If a bacterial etiology is confirmed and an disinfectant agent is indicated or has been used, susceptibility test may reveal whether the worsening symptoms could be due to disinfectant agent underground .
persistent symptoms ( > 14 days after onset ) may end for months or even years and may respond to a exchangeable management scheme. Protozoa ( including Cryptosporidium species, Cyclospora cayetanensis, Cystoisospora belli, and Giardia lamblia ) and microsporidia are considerations, particularly in an immunocompromised host. diagnosis of these pathogens ( mesa 5 ) optimally is performed via microscopy or antigen detection. discussion, where possible or advisable, is outlined in mesa 6. When assessments for infectious agents do not yield an etiology, consideration of noninfectious illnesses and incendiary processes should occur [ 152 ]. Both IBD and celiac disease are considerations. Postinfectious functional gastrointestinal disorders, including excitable intestine syndrome ( PI-IBS ), may occur in 3 % –10 % of adults following bacterial diarrhea. Symptoms attributable to PI-IBS by and large resolve within 1 year, but may persist for several years. judgment and management by a gastroenterologist for these conditions should be considered .
Although authoritative studies are lacking, molecular-epidemiologic assessments and outbreak investigations suggest that reinfection with enteric pathogens and possible recurrence of clinical symptoms are more probably to occur among people who reside in push settings with impair access to pass hygiene. Recurrent diagnostic infections are more likely to occur with enteric pathogens with higher rates of infectivity and when cross-protection to infection with early strains does not result from an infection with one tense or serovar .
assessment of dose of an antimicrobial agentive role to ensure that therapeutic levels are or were achieved may be indicated. In some situations, adjunctive therapy such as a probiotic may be beneficial in restoration of dysbiosis due to the pathogen or treatment [ 153 ]. The government of nitazoxanide has resulted in decrease of clinical symptoms in nonresponders and people with persistent symptoms [ 154, 155 ]. nutritional rehabilitation and fluid and electrolyte administration are the mainstays of management, with a preference for intestinal administration when tolerated .
noninfectious etiologies of diarrhea should be considered if an individual with a worsening clinical course remains unresponsive to management. Imaging, including colonoscopy or endoscopy, may be indicated and consultation with a gastroenterologist may be beneficial in directing evaluation in the worsening server .
The perseverance of organisms in the gastrointestinal nerve pathway as detected by stool assessments varies by organism and host factors. While asymptomatic shed may result in transmission of an organism from person to person, the more clinically relevant exit relates to an infection that results in clinical symptomatology. In people who are able to practice meticulous hand hygiene and who are not employed in a fructify where transmission could result in a hard infection or outbreak, insistent test will not result in clinical profit and will be damaging in terms of cost and use of limited healthcare resources. When the solution ( mho ) of testing will not impact management, follow-up examination should be deferred. however, in situations where discussion failures are more probably to occur or the infect pathogen has demonstrated multidrug resistance, a test of cure may be beneficial .

Empiric Management of Infectious Diarrhea

XI. When is empiric antibacterial treatment indicated for children and adults with bloody diarrhea and, if indicated, with what agent?

  1. What are modifying conditions that would support antimicrobial treatment of children and adults with bloody diarrhea?
  2. In which instances should contacts be treated empirically if the agent is unknown?
Recommendations (Table 6)
  1. In immunocompetent children and adults, empiric antimicrobial therapy for bloody diarrhea while waiting for results of investigations is not recommended (strong, low), except for the following:
    1. Infants <3 months of age with suspicion of a bacterial etiology.
    2. 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.
    3. People who have recently travelled internationally with body temperatures ≥38.5°C and/or signs of sepsis (weak, low). See https://wwwnc.cdc.gov/travel/yellowbook/2016/the-pre-travel-consultation/travelers-diarrhea.
  2. 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 (strong, moderate). 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 (strong, moderate).
  3. Empiric antibacterial treatment should be considered in immunocompromised people with severe illness and bloody diarrhea (strong, low).
  4. 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 (strong, moderate).
  5. 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 (strong, low). Antimicrobial therapy should be narrowed when antimicrobial susceptibility testing results become available (strong, high). 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 (weak, low).
  6. 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 (strong, moderate). 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 (strong, low).
Evidence Summary

intestinal perforation and death were more common in case series of patients with typhoid fever in the preantibiotic era ( before 1950 ) than in the antibiotic era ( after 1950 ) [ 156 ]. Patients with enteric fever treated early on in their clinical courses have better outcomes than patients treated late [ 157 ]. Time to loss of fever was longer and case fatality proportion was higher among series of patients receiving supportive treatment only and patients receiving low doses of appropriate antimicrobial therapy compared with patients receiving commend doses [ 158 ] .
In adults, as in children, bloody diarrhea can be due to infectious and noninfectious causes. The presence of fever, abdominal pain, or vomiting is more implicative of infection, which in these cases is likely to be due to an invasive/inflammatory pathogen. The most normally identified pathogens in this category in North America are Salmonella, Campylobacter, C. difficile, Shigella, and STEC. several RCTs specifically examining the profit of empiric treatment of adults with acute, severe diarrhea, overall have demonstrated an average of 1 day shorter symptoms with an disinfectant agent compared with placebo. however, these data are considered low quality due to incompatibility and indirectness. The antimicrobial agents utilized in the most late of these studies were fluoroquinolones ; previous data on trimethoprim-sulfamethoxazole ( TMP-SMX ) are not considered applicable today because of high rates of resistance. In general, the largest treatment effect was seen in patients with salmonellosis, followed by campylobacteriosis, but disinfectant treatment besides was accompanied by an increase in drawn-out Salmonella desquamation and episodic shed of quinolone-resistant Campylobacter. furthermore, the benefit of antimicrobial treatment of rise Campylobacter infection is small, and disinfectant agents are not recommended for most cases of prove Salmonella diarrhea. Given that the huge majority of incendiary infectious diarrhea episodes are self-limited and that the treatment benefit is modest, in most cases the risks of treatment outweigh the benefits. Exceptions may occur in severe infections and in infections occurring in immunocompromised hosts. Severe CDIs have doubled in incidence since 2001 and can mimic other forms of infectious colitis. While most cases are associated with healthcare and holocene disinfectant agent use, there has been an increase in community-acquired cases with minimal or even no antimicrobial agent exposure. Use of attendant antimicrobial agents is associated with decreased bring around rates and higher relapse rates in CDI .
STEC infections besides must be a retainer in any patient with bally diarrhea, even when fever is confront, but peculiarly when it is lacking. discussion of STEC O157 infections and likely non-O157 STEC infections that produce Shiga toxin 2 with fluoroquinolones, β-lactams, TMP-SMX, and metronidazole in patients of all ages should be avoided because of testify of harm. Although very limited data are available on the potential risks or benefits associated with treating people with these infections with macrolide antibiotics, insufficient evidence of benefit and some testify for injury favors avoidance of these agents among people infected with STEC O157 or early STEC that produce Shiga toxin 2 [ 159 ]. Insufficient data are available to assess the risks and benefits associated with treating less deadly STEC infections ( internet explorer, STEC that do not produce Shiga toxin 2 ) with antibiotics. however, because the Shiga toxin profile is much stranger when discussion is considered and because no clear benefit exists for treating patients with diarrhea caused by less deadly STEC infections with antibiotics, avoidance of antibiotic treatment is recommended .
several RCTs have demonstrated a small but meaning benefit for antimicrobial therapy in reducing the duration of symptoms in Campylobacter gastroenteritis. A meta-analysis confirmed an average of 1 day shorter duration of illness with fluoroquinolone or macrolide discussion compared with placebo [ 160 ]. however, symptoms in all cases in these studies were self-limited and the treatment effect appeared to be largest in patients treated early in the illness course. Earlier, directed treatment may become more feasible with the increasing use of CIDT, facilitating organism identification. furthermore, there is no evidence that antimicrobial therapy prolongs the carrier department of state or encourages clinical relapses in campylobacteriosis, so the hazard of treatment is relatively small. Although quinolone underground may develop during therapy, person-to-person ranch of drug-resistant Campylobacter is not believed to be a common scenario. Hence, it is fair to treat patients with particularly prolonged or hard disease. black Campylobacter infections remain rare, but are more common in sternly immunocompromised hosts, and despite the miss of evidence, it is reasonable to offer treatment to immunocompromised patients with otherwise uncomplicated Campylobacter gastroenteritis .
The choice of disinfectant agent may change due to evolving electric resistance patterns [ 161 ]. Fluoroquinolone resistance in US and canadian patients without international travel remains humble, but is significantly higher in many normally visit countries ( ranging from 56 % in Mexico to > 92 % in Thailand ) [ 162, 163 ]. Macrolide resistance remains much less coarse ( < 5 % among human isolates in the United States [ 164 ] ). Hence, azithromycin can be recommended as primary treatment for traveler ’ s diarrhea in Thailand based on randomize trial data, and besides should be considered first-line treatment for Campylobacter infection in travelers to other locations unless fluoroquinolone susceptibility is confirmed. other disinfectant agents that may be effective in individual Campylobacter isolates include TMP-SMX and tetracyclines, although in general, underground rates are well higher and there is no advantage to these agents over azithromycin .

XII. When is empiric treatment indicated for children and adults with acute, prolonged, or persistent watery diarrhea and, if indicated, with what agent?

  1. What are modifying conditions that would support empiric antimicrobial treatment of children and adults with watery diarrhea?
  2. In which instances, if any, should contacts be treated empirically if the agent is unknown?
Recommendations (Table 6)
  1. In most people with acute watery diarrhea and without recent international travel, empiric antimicrobial therapy is not recommended (strong, low). 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 lasting 14 days or more (strong, low).
  2. 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 (strong, moderate).
Evidence Summary

Watery diarrhea can be the basal demonstration of either an incendiary or non-inflammatory intestinal tract infection. The presence of high fever or meaning abdominal annoyance, and duration > 3 days are indicative of inflammatory infection with indications for investigation ( table 3 ). While several RCTs have shown a benefit of empiric treatment prior to culture results in these cases, the tell is of low quality ascribable to inconsistency and indirectness. Combined with the relatively small benefit of empiric treatment ( 1 day shorter illness on average ), empiric treatment can not be recommended. In the absence of signs and symptoms to suggest incendiary bacterial infection, viral infection becomes significantly more probable and antimicrobial discussion is ineffective and potentially harmful, making empiric discussion tied less desirable .
dogged reeking diarrhea by and large should not be treated in the absence of an identified campaign. This syndrome in otherwise healthy adults and children is only rarely due to bacterial infection, and bacteria that are reported to be associated with drawn-out diarrhea ( such as Aeromonas, Plesiomonas, C. difficile, and EAEC ) are much not detected on routine stool culture. When haunting diarrhea is caused by infection, the most common etiological agents are protozoal ( including parasites such as Giardia lamblia, Cryptosporidium species, Cyclospora cayetanensis, and Cystoisospora belli, depending in separate on the epidemiologic setting ) and are best managed with pathogen-specific therapy ( quite than empiric therapy before the infection is diagnosed ). One exception to this is haunting diarrhea in patients who are sternly immunocompromised ( including people with AIDS ), in which more conventional pathogens such as Campylobacter and Salmonella may persist. While it remains preferable to identify a specific cause in these cases, there are situations where an empiric test with an disinfectant agent may be considered to provide symptomatic profit to optimize tolerance of highly active antiretroviral therapy .

Directed Management of Infectious Diarrhea

XIII. How should treatment be modified when a clinically plausible organism is identified from a diagnostic test?

Recommendation
  1. Antimicrobial treatment should be modified or discontinued when a clinically plausible organism is identified (strong, high).
Evidence Summary

Recommendations for disinfectant agents by pathogen with first and alternative choices are listed in table 6 for normally identified bacterial ( Campylobacter, C. difficile, nontyphoidal Salmonella, Shigella, Vibrio cholerae, non–Vibrio cholerae, Yersinia enterocolitica ) and other organisms ( Cryptosporidium, Cyclospora, Giardia, Cystoisospora, and microsporidia ) .

Supportive Treatment

XIV. How should rehydration therapy be administered?

Recommendations (Table 7)
  1. 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 (strong, moderate), and in people with mild to moderate dehydration associated with vomiting or severe diarrhea.
  2. 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 (weak, low).
  3. 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 (strong, high) or ileus (strong, moderate). In people with ketonemia, an initial course of intravenous hydration may be needed to enable tolerance of oral rehydration (weak, low).
  4. In severe dehydration, intravenous rehydration should be continued until pulse, perfusion, and mental status normalize and the patient awakens, has no risk factors for aspiration, and has no evidence of ileus (strong, low). The remaining deficit can be replaced by using ORS (weak, low). Infants, children, and adults with mild to moderate dehydration should receive ORS until clinical dehydration is corrected (strong, low).
  5. 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 (strong, low).
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Evidence Summary

refilling of water, electrolytes, and nutrients lost during diarrhea is substantive in the management of diarrhea. During diarrhea, the coupled transport of sodium and glucose across the intestinal brush surround remains integral, and leads to enhanced water absorption, enabling oral rehydration. oral rehydration has been credited with saving millions of lives in the management of dehydration in all old age groups, careless of the cause, and is recommended by the WHOs and as the first line of rehydration [ 165 ] .
The safety and efficacy of ORS, in comparison to intravenous rehydration therapy ( IVT ), was evaluated in a meta-analysis of 17 RCTs involving 1811 patients aged < 18 years from high-income and low-income countries. There were no important clinical differences in bankruptcy to rehydrate, weight profit at discharge, hyponatremia or hypernatremia, duration of diarrhea, or entire fluid intake at 6 or 24 hours between children receiving ORS and IVT. phlebitis occurred more often in children receiving IVT, and paralytic intestinal obstruction occurred more often with ORS ( though the latter dispute was not statistically different ). The model estimated that 4 % of children treated with ORS would fail and require IVT [ 166 ] . standard WHO-ORS ( osmolarity 311 mmol/L ) was the recommend agent for several decades [ 167 ]. Despite its ability to hydrate, WHO-ORS had limitations, including inability to reduce the volume or duration of diarrhea, and concerns that it could lead to hypernatremia, particularly in noncholera diarrhea in which salt losses are reduced. In 2002, a hypotonic oregon with total osmolarity < 250 mmol/L was recommended by the WHO and subsequently by respective other advisory bodies as first-line therapy for meek to moderate dehydration caused by diarrhea of all causes [ 168 ]. In a meta-analysis of 14 RCTs involving children < 5 years of age with diarrheal dehydration ( all causes ) from low- and high-income countries, reduced osmolarity ORS was associated with fewer unscheduled infusions [ 165 ], reduced fecal matter output, and decreased vomiting compared with WHO-ORS. In a meta-analysis of adults and children with cholera, reduced osmolarity ORS ( ≤270 mmol/L ) was associated with more biochemical hyponatremia compared with WHO-ORS ( osmolarity ≥310 mmol/L ), although no significant differences in good consequences were noted based on the 4 RCTs included in the analysis [ 169 ]. Recipients of a polymer-based oral rehydration solution demonstrated fewer unscheduled intravenous infusions compared with pediatric recipients of WHO-ORS ≥310 mmol/L who had acute accent reeking diarrhea or diarrhea attributed to a cholera contagion. The polymer-based ORS was besides favored over the hypo-osmolar ORS ≤270 mmol/L, although there were insufficient data to adequately ability the analysis [ 170 ]. ORS is an integral part of rehydration and may be used effectively in combination with intravenous therapy and with passage to intestinal feed .

XV. When should feeding be initiated following rehydration?
Recommendations
  1. Human milk feeding should be continued in infants and children throughout the diarrheal episode (strong, low).
  2. Resumption of an age-appropriate usual diet is recommended during or immediately after the rehydration process is completed (strong, low).
Evidence Summary

early studies showing that children who resumed feeding during or after rehydration had improved nutritional result [ 171 ] led to multiple guidelines supporting this exercise. A meta-analysis ( 12 RCT, most performed 20 years ago and for which coverage of methodology was incomplete ) showed that early feed ( within 12 hours of beginning rehydration ) was as condom and effective as later feeding among children aged < 6 years honest-to-god with acuate diarrhea from low-, middle-, and high-income countries [ 172 ]. There was no significant dispute between early and late refeeding groups in the motivation for unscheduled intravenous therapy, number of children with vomit and dogged diarrhea, and duration of hospital arrest. Data were insufficient to assess differences in duration of diarrhea, stool end product, or weight amplification. A meta-analysis of 33 trials involving children < 5 years of age with acute diarrhea ( by and large inpatients from high- and middle-income countries ) found that a lactose-free diet reduced the duration of diarrhea by an average of 18 hours and boil down treatment failure ( continued or worsening diarrhea or vomit, the necessitate for extra rehydration, or continuing burden loss ) by one half [ 173 ]. In adults, early refeeding decreases intestinal permeability caused by infections, reduces illness duration, and improves nutritional outcomes. This is particularly authoritative in low- and middle-income countries, where underlying preexisting malnutrition is often a factor. Although the BRAT ( bananas, rice, folderol, and toast ) diet and the avoidance of dairy are normally recommended, supporting data for those interventions are limited. Instructing patients to refrain from eating solid food for 24 hours besides does not appear to be utilitarian [ 174 ] .

Ancillary Management

XVI. What options are available for symptomatic relief, and when should they be offered?

Recommendations
  1. 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 (weak, low).
  2. Antimotility drugs (eg, loperamide) should not be given to children <18 years of age with acute diarrhea (strong, moderate). Loperamide may be given to immunocompetent adults with acute watery diarrhea (weak, moderate), but should be avoided at any age in suspected or proven cases where toxic megacolon may result in inflammatory diarrhea or diarrhea with fever (strong, low).
  3. Antinausea and antiemetic (eg, ondansetron) may be given to facilitate tolerance of oral rehydration in children >4 years of age and in adolescents with acute gastroenteritis associated with vomiting (weak, moderate).
Evidence Summary

accessory discussion for acute accent infectious diarrhea includes antimotility and antisecretory agents to shorten duration of diarrhea in adults, and antiemetic agents to facilitate oral rehydration in people with significant vomiting. oral rehydration has been shown to be useful in all ages, and antiemetics such as dimenhydrinate have been beneficial in adults. Ondansetron is a serotonin 5-HT3 receptor antagonist used for discussion of nausea and vomit in respective settings [ 175 ]. During acute gastroenteritis, studies have shown that more children receiving ondansetron, compared with placebo, had resolution of vomiting ; ondansetron reduced the immediate necessitate for hospitalization insurance or intravenous rehydration [ 176 ]. however, ondansetron did not decrease hospitalization insurance rates at 72 hours after discharge from the emergency department. There was no significant increase in adverse events, but diarrhea was reported as a side impression of ondansetron discussion in respective studies [ 177–179 ]. Ondansetron can reduce vomiting in children and reduce the necessitate for hospitalization for rehydration, although it may increase stool volume. A recommendation can not be made for the routine manipulation of antiemetic agents for acute gastroenteritis in children < 4 years of old age or in adults. Bismuth subsalicylate is mildly effective. Racecadotril reduces stool volume but is not available in North America [ 180, 181 ] . Loperamide is a locally acting opioid sense organ agonist that decreases the muscular tone and motion of the intestinal wall. In children with meek to moderate dehydration associated with by and large nonbacterial pathogens, a meta-analysis of earlier studies has shown that loperamide reduced diarrhea preponderance at both 24 and 48 hours after attack of treatment, and reduced the full duration of diarrhea [ 182 ]. These studies excluded children with control to severe dehydration ( or some did not include hydration condition ) and bloody diarrhea. adverse events including intestinal obstruction, abdominal distention, and inanition tended to occur in subjects receiving discussion. Deaths have been reported in 0.54 % of children given loperamide, and all of these events occurred in children < 3 years old. In healthy adults, loperamide has been shown to be effective in reducing diarrhea, but most of the studies have been focused on travelers to resource-challenged countries and the drug was used in combination with disinfectant agents [ 183 ]. In these studies, loperamide was not associated with increased happening of adverse events. Loperamide importantly reduces toilet volume in traveler ’ second diarrhea and in most noncholera watery diarrhea syndromes . Patients should be advised about medications with the potential to increase the risk of complications from diarrhea, particularly antidiarrheal and antimicrobial agents. limited reports suggest that act habit of medications with anticholinergic properties may lead to increased hazard of severe outcomes, including death, from diarrhea caused by C. difficile and Clostridium perfringens, a toxin-mediated illness [ 91, 184, 185 ]. clinical conditions besides have worsened following administration of antimotility agents to patients with shigellosis and infection with STEC. antimicrobial agents and antidiarrheal medications administered to people with diarrhea caused by STEC infections may increase the risk of HUS .

XVII. What is the role of a probiotic or zinc in treatment or prevention of infectious diarrhea in children and adults?

Recommendations
  1. Probiotic preparations may be offered to reduce the symptom severity and duration in immunocompetent adults and children with infectious or antimicrobial-associated diarrhea (weak, moderate). Specific recommendations regarding selection of probiotic organism(s), route of delivery, and dosage may be found through literature searches of studies and through guidance from manufacturers.
  2. 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 (strong, moderate).
Evidence Summary

Most trials report that probiotics decrease diarrhea duration and stool frequency with a sustain beneficial effect across all outcomes. No adverse events have been directly attributable to probiotics in healthy recipients ; case reports of bacteremia or fungemia with molecularly matched isolates to the probiotic organism have occurred in critically ill or immunocompromised people. The interpretations of many studies are limited by statistical heterogeneity due to varying definitions of diarrhea, consequence measurements, probiotic product, discussion regimens, participants, and settings [ 186 ] .
Despite the limitations of meta-analyses, a reduction in base duration of diarrhea by 25 hours ( 95 % confidence interval, 16–34 hours ) was noted among 455 participants in 35 trials ; a decrease in the gamble of diarrhea with a duration > 4 days was noted among 2850 participants enrolled in 29 trials ; and a reduction in stool frequency was noted on the second day of symptoms among 2751 participants enrolled in 20 trials. overall, efficacy of probiotic supplementation was greater for participants with an identified viral etiology of diarrhea. however, this may be due to the fact that diarrhea of a viral etiology is more prevailing than that of a bacterial etiology [ 177, 187–190 ] .
In a meta-analysis of 24 RCTs by and large conducted in Asia and in resource-limited settings, oral zinc supplementation appeared to shorten the duration of acute accent diarrhea in children who are 6 months to 5 years of senesce by 10 hours with an even greater reduction ( 27 hours ) among children who have signs of malnutrition [ 191 ]. The impression on hospitalization insurance and death could not be measured. The duration of treatment of persistent diarrhea was shortened by about 16 hours. Vomiting was noted to be more park in infants and children who received zinc supplementation compared with children who were not given zinc. An RCT among polish children 3–48 months of senesce with acute diarrhea did not find a significant benefit from a 10-day course of zinc on the duration of diarrhea [ 192 ]. An RCT evaluating the efficacy of a 14-day course of zinc in US outpatients and inpatients aged 6 months to 6 years with acute diarrhea is ongoing [ 193 ] .

XVIII. Which asymptomatic people with an identified bacterial organism from stool culture or molecular testing should be treated with an antimicrobial agent?

Recommendation
  1. Asymptomatic people who practice hand hygiene and live and work in low-risk settings (do not provide healthcare or child or elderly adult care and are not food service employees) do not need treatment, except asymptomatic people with Salmonella enterica subspecies enterica serovar Typhi in their stool who may be treated empirically to reduce potential for transmission (weak, low). Asymptomatic people who practice hand hygiene and live and work in high-risk settings (provide healthcare or child or elderly adult care and are food service employees) should be treated according to local public health guidance (strong, high).
Evidence Summary

Adults with acute accent nontyphoidal Salmonella enterica diarrhea normally continue to sporadically shed the organism in stool asymptomatically for weeks [ 194 ]. Although there is a gamble of these individuals spreading contagion to others, peculiarly through food cover and close contact, outbreak related to known carriers appear to be rare, and can be avoided through proper hand hygiene [ 195, 196 ]. The only randomized trial of decolonization was in Thailand, where antimicrobials failed to show a benefit over placebo, although reacquisition preferably than doggedness may have explained this failure [ 197 ]. Despite the dearth of evidence, some state and local laws mandate negative fecal matter cultures prior to resuming work ; in these situations, treatment may be considered .
asymptomatic shedding of Salmonella serovar Typhi after acuate infection is quite common, and can persist beyond a year in a small share of patients. These chronic carriers can spread contagion to others if proper hand hygiene practices are not followed. One small randomized, controlled test and one nonrandomized trial have showed high efficacy rates for decolonization with fluoroquinolones [ 198, 199 ] .

Prevention

XIX. What strategies, including public health measures, are beneficial in preventing transmission of pathogens associated with infectious diarrhea?

Recommendations
  1. 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 (strong, moderate).
  2. 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 (strong, high). 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 (strong, low). See https://www.cdc.gov/hicpac/2007IP/2007isolationPrecautions.html.
  3. 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 (strong, moderate).
  4. Healthcare providers should direct educational efforts toward all people with diarrhea, but particularly to people with primary and secondary immune deficiencies, pregnant women, parents of young children, and the elderly as they have increased risk of complications from diarrheal disease (strong, low).
  5. Ill people with diarrhea should avoid swimming, water-related activities, and sexual contact with other people when symptomatic while adhering to meticulous hand hygiene (strong, low).
Evidence Summary

infectious agents that cause diarrhea are transmitted predominately by the fecal-oral road. Organisms in fecal matter are transmitted to a susceptible host through touch transmission via contamination of inanimate surfaces, the hands of septic people and their caregivers, and vectors such as water or food, and contact with animals or their environment. The infect person may be shedding organisms in diarrheal stool, be in the convalescent phase of a diarrheal illness, or have asymptomatic spill. Standard practices and transmission-based, or extra precautions, are the initiation for preventing transmission of infectious agents in the healthcare setting [ 200 ] and provide respective infection control measures for all patient wish settings. Standard practices are used at all times, whereas extra precautions are implemented based on patient symptoms or signs and/or diagnoses of certain microorganisms. For model, as part of standard practices, healthcare providers exercise hand hygiene before and after each patient touch, use personal protective equipment depending on the affected role care action, and play along recommendations regarding affected role placement and environmental clean. A patient with diarrhea would be placed on liaison, in addition to standard, precautions. The lector is referred to detailed guidelines of the CDC ’ second Healthcare Infection Practices Advisory Committee for far information about the specific infection command measures for contact precautions and with particular diarrheal agents [ 200 ] .
In the residential district, transmission of diarrheal pathogens can be interrupted by access to clean water and appropriately handled food, vitamin a well as hand hygiene before and after each contact with the ill person or their soundbox fluids. This includes appropriate hand hygiene after using the toilet, after handling diapers at home and in out-of-home child caution [ 201 ], before and after preparing food, before feed, and after handling patients ’ personal items, or after touching pets or animals or their feces or environments, peculiarly in public settings ( such as petting menagerie and public farms ) [ 202 ]. The spread of infectious diarrhea in child care settings can be decreased by training child caution providers in infection operate procedures, maintaining cleanliness of surfaces, keeping food preparation duties and areas separate from child care activities and exercising adequate hired hand hygiene, cohorting ill children, and excluding ill child care providers and food handlers. Alcohol-based hand hygiene is recommended, unless there is visible soiling, in which font hand hygiene with water system and soap is necessity. When Cryptosporidium, norovirus, or a known spore-forming pathogen such as C. difficile is an infect agent, hand hygiene with soap and water may be more effective than practice of an alcohol-based sanitizer [ 203 ]. Some diarrheal agents are reportable to public health authorities ( See Question XXI ), and populace health may place infect food handlers, amateur water staff, healthcare providers, or child care providers on furlough until the risk of transmission is eliminated or reduced .
The CDC recommends that no one consume or drink unpasteurized dairy products or undercooked kernel. specific groups of patients have increased risk of complications with diarrheal disease and sanction specific attention to education about diarrheal disease hazard, such as the immunocompromised, pregnant women, people with chronic liver-colored disease, the aged, and parents caring for young infants. education with attention to the especial epidemiology of gamble for that person and/or their health professional should be provided by healthcare providers. information on food safety can be found at the US Department of Health and Human Services [ 204 ] .

XX. What are the relative efficacies and effectiveness of vaccines (rotavirus, typhoid, and cholera) to reduce and prevent transmission of pathogens associated with infectious diarrhea, and when should they be used?

Recommendations
  1. Rotavirus vaccine should be administered to all infants without a known contraindication (strong, high).
  2. 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 Salmonella enterica subspecies enterica serovar Typhi, people with intimate exposure (eg, household contact) to a documented Salmonella enterica subspecies enterica serovar Typhi chronic carrier, and microbiologists and other laboratory personnel routinely exposed to cultures of Salmonella enterica subspecies enterica serovar Typhi (strong, high). Booster doses are recommended for people who remain at risk (strong, high).
  3. 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 (strong, high). See https://www.cdc.gov/cholera/vaccines.html.
Evidence Summary

anterior to introduction of rotavirus vaccine programs in the United States in 2006, rotavirus was the leading campaign of acute accent gastroenteritis, resulting in medical visits and hospitalization insurance in children < 5 years of old age. Following boastfully phase 3 trials demonstrating efficacy of vaccine against any rotavirus infection of 74 % –87 %, and against hard gastroenteritis of 85 % –98 %, universal baby rotavirus inoculation was recommended by ACIP [ 202 ]. Rotavirus surveillance has demonstrated significant reductions in outpatient visits and hospitalization, deoxyadenosine monophosphate well as evidence of profit in nonimmunized older people [ 23 ]. Two alive, attenuated orally administered rotavirus vaccines are available in the United States : a pentavalent rotavirus vaccine ( Rotateq, Merck ) given in a 3-dose agenda, and a monovalent vaccine ( Rotarix, GSK ) given in a 2-dose schedule . presently, there are 2 license vaccines in the United States for prevention of typhoid fever, each offering 50 % –80 % protection [ 26 ]. Typhoid vaccination is recommended for travelers to areas where there is increased risk for exposure to Salmonella Typhi. The Ty21a vaccine is a know, attenuate, oral vaccine containing the Salmonella Typhi try. Ty21a available as enteric capsules and is licensed in the United States for habit in immunocompetent people including children ≥6 years of old age ; the recommend promote interval is every 5 years. The parenteral Vi-polysaccharide vaccine is licensed in the United States for children ≥2 years of old age and adults. The recommend promote interval is every 2 years. Typhoid vaccines do not offer protection against Salmonella Paratyphi A, B, or C infection . CVD 103-HgR is a live, attenuated single-dose oral cholera vaccine available for adults in the United States who plan to travel to cholera-affected areas, defined as areas of endemic cholera transmission, outbreak ( epidemic ), or recent bodily process ( within the past year ). Two demobilize oral vaccines are available in other countries. Cholera immunization is not required for travelers entering the United States from cholera-affected areas, and the WHO no longer recommends immunization for travel to or from areas with cholera infection. No state requires cholera vaccine for submission .

XXI. How does reporting of nationally notifiable organisms identified from stool specimens impact the control and prevention of diarrheal disease in the United States?

Recommendation
  1. 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 (eg, Salmonella, STEC, Shigella, and Listeria) to ensure that control and prevention practices may be implemented (strong, high).
Evidence Summary

Clinical healthcare providers and public health practitioners have overlapping interests in and responsibilities for diagnosis, management, and prevention of infectious diarrhea. For clinicians, early diagnosis of an acute sequence of diarrhea can occasionally result in interventions that alleviate symptoms and reduce secondary coil transmission. For public health practitioners, prompt presentment of pathogen-specific diagnoses and molecular test of isolates obtained through populace health surveillance can lower rates of infection and lead to seasonably detection and restraint of outbreaks. To reduce the unwholesomeness and mortality associated with infectious diarrhea, the clinical and populace health practitioner communities must work closely together to identify optimum diagnostic, treatment, and prevention methods .
Public health officials at US state and territorial health departments and the CDC collaborate in determining which diseases should be nationally notifiable, arsenic well as timeframes for reporting. The Council of State and Territorial Epidemiologists, with advice from the CDC, makes recommendations per annum for additions and deletions to the list of nationally notifiable diseases. Clinicians, hospitals, and laboratories in the United States are required to report diseases, conditions, or outbreak as determined by local, state, or territorial jurisprudence or regulation, as outlined in each jurisdiction ’ randomness list of reportable conditions. Additional and specific report requirements should be obtained from the appropriate local, submit, or territorial health departments .
Reports of certain infections to public health authorities should be accompanied by submission of an isolate to the public health lab. promote word picture of some infecting pathogens in public health laboratories has been critical to identifying, stopping, and preventing many dispersed outbreaks through laboratory-based surveillance that utilizes isolate subtyping to detect outbreaks caused particular strains [ 123 ]. This type of surveillance began in the 1960s with serotyping of Salmonella isolates. In the 1990s, more discriminatory subtyping was introduced through pulsed-field gel electrophoresis, with the second coming of the PulseNet surveillance system [ 123 ]. In late years, higher resolution subtyping such as whole-genome sequence is being performed by public health laboratories to detect outbreaks even more promptly [ 205 ]. The affect of these techniques on surveillance systems has been huge, including the passing of the Food Safety Modernization Act, and the development of new standards for beef and poultry by the US Department of Agriculture. Continuing to detect and respond to such outbreaks is a vital part of making our food and body of water systems safer. As CIDT diagnostic panels become used more frequently, public health departments may request that specimens be cultured in populace health laboratories if unable to be cultured in the clinical diagnostic lab .
While laboratory-based surveillance like PulseNet is critical to detecting outbreaks, particularly those consisting of widely dispersed infections, most diarrheal disease outbreaks are localized events and are much detected by the astute clinician [ 123 ]. therefore, healthcare providers should adhere to local anesthetic and country report requirements regarding any unusual cluster of diarrheal illness, regardless if an etiology has been determined or if the settle etiologies are typically not reportable, so that see measures may be implemented and the pathogen and reference of contagion identified to guide appropriate contraceptive strategies specific to the residential district at risk .
Attempts to detect pathogens in people with diarrhea provide public health profit ( beyond those described in the diagnostics section above ) in which the individual may either serve as the lookout font of an outbreak or serve as a risk for the initiation of an outbreak. People who work in healthcare, specially but not limited to those who provide concern for immunocompromised people ( HIV infected, those with cancer, or transplant recipients ) should undergo diagnostic testing when diagnostic. early situations in which diagnostic stool evaluation may be appropriate include child wish providers ( adult or child ), child concern attendees ( adult or child ), people involved in food homework or delivery, people who work at recreational water facilities, or people who work at or live in residential facilities such as residential or group homes, prisons, or long-run concern facilities. Cruise ships besides have been associated with outbreaks of gastrointestinal tract illness, including diarrhea. If an outbreak is suspected ( in a school, college dormitory, or natural process group ), the health official in charge should consider obtaining diagnostic testing to optimize interposition. Culture-dependent investigations, when a bacterial pathogen is involved, can assist in determining resistance patterns of enteric pathogens circulating in the community to permit development of appropriate treatment or management regimens .
All organisms listed in the mesa of Infectious Diseases Designated as Notifiable at the National Level ( hypertext transfer protocol : //wwwn.cdc.gov/nndss/ ) should be reported. The CDC acts as a coarse depository for states and territories for collecting data and coverage of nationally notifiable diseases. Reports of occurrences of nationally notifiable diseases are transmitted to the CDC each week from the 50 US states, 2 cities ( Washington, District of Columbia and New York, New York ) and 5 territories ( american Samoa, Commonwealth of Northern Mariana Islands, Guam, Puerto Rico, and the US Virgin Islands ). Provisional data are published hebdomadally in the Morbidity and Mortality Weekly Report ; final data are published each class by the CDC in the annual “ Summary of Notifiable Diseases, United States ” [ 206 ]. The opportuneness of the probationary hebdomadally reports, in summation to laboratory-based surveillance, provides information that the CDC and state or local epidemiologists use to detect disease happening and more effectively interrupt outbreaks. The finalize annual data provide data on reported disease incidence that is necessary for report of epidemiologic trends and development of disease-prevention policies. The CDC is the sole repository for these national data, which are used widely by local anesthetic, express, and federal populace health and other agencies .
The postdate 13 conditions, which are associated with infectious diarrhea, are included in the table of Infectious Diseases Designated as Notifiable at the National Level—United States, 2017 :

  • Campylobacteriosis
  • Cholera
  • Cryptosporidiosis
  • Cyclosporiasis
  • Giardiasis
  • Hemolytic-uremic syndrome, postdiarrheal
  • Salmonellosis
  • Shiga toxin–producing Escherichia coli
  • Shigellosis
  • Trichinellosis (trichinosis)
  • Typhoid fever
  • Vibriosis
  • Foodborne disease outbreak

Future Directions

A keystone challenge in the diagnosis and management of people with infectious diarrhea is the use and interpretation of molecular-based diagnostics. Differentiating colonization from active contagion, obtaining disinfectant susceptibility results, providing optimum management, and preventing transmission are areas in necessitate of extra research as nonculture diagnostics replace traditional culture-based methods. Despite the development of diagnostics, the optimum management of people with infectious diarrhea centers on obtaining a thorough exposure history and performing a physical examination. This information enables the clinician to selectively apply diagnostics and judiciously administer therapy. Interrupting infection of catching enteric infections is all-important in preserving populace health .

Notes

Financial Support

documentation for these guidelines was provided by the infectious Diseases Society of America .

Acknowledgments

The expert panel expresses its gratitude for thoughtful reviews of an earlier version by Drs Herbert Dupont, Richard L. Guerrant, and Timothy Jones. The dialog box thanks the IDSA for supporting guideline development, and specifically Vita Washington for her continue support throughout the guidepost serve. Appreciation is expressed to Dr Nathan Thielman for his contributions to the initial stages of guidepost development and Dr Faruque Ahmed for his cover support and steering regarding the GRADE system. many thanks to Reed Walton for her aid at many levels, William Thomas for aid with the literature review, and Bethany Sederdahl for her column aid .

Disclaimer

The findings and conclusions in this composition are those of the authors and do not necessarily represent the official side of the Centers for Disease Control and Prevention .

Potential Conflicts of Interest

The watch list is a observation of what has been reported to the IDSA. To provide thorough transparency, the IDSA requires full disclosure of all relationships, careless of relevance to the guideline subject. evaluation of such relationships as potential conflicts of interest is determined by a review work which includes judgment by the SPGC Chair, the SPGC affair to the development panel and the Board of Directors liaison to the SPGC and if necessary, the Conflicts of Interest ( COI ) Task Force of the Board. This assessment of disclosed relationships for possible COI will be based on the proportional weight of the fiscal relationship ( internet explorer, monetary amount ) and the relevance of the relationship ( i, the degree to which an association might sanely be interpreted by an autonomous observer a related to the topic or recommendation of retainer ). The reader of these guidelines should be mindful of this when the tilt of disclosures is reviewed. The institution at which A. L. S. has received research grants from the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases ( NIAID ), and the Gerber Foundation, from which she has received wage support, and she has received honoraria from SLACK and travel subsidies from International Scientific Association for Probiotics and Prebiotics ( hypertext transfer protocol : //isappscience.org/ ) to attend annual meetings, J. C. has received inquiry grants from the US Army, and stocks and bonds from Ariad and SIS Pharmaceuticals. A. C. has received research grants from CSL Behring and National Health & Medical Research. J. A. C. has received research grants from the CDC, National Institutes of Health ( NIH ), UK Biotechnology and Biological Sciences Research Council, Bill & Melinda Gates Foundation, and New Zealand Health Research Council. J. M. L. ’ mho institution has received research grants from Merck, GlaxoSmithKline, the Canadian Institutes of Health Research ( CIHR ), Pfizer, PCIRN, Dynavax, and Afexa. T. S. has received research grants from Merck, Crohn ’ sulfur and Colitis Canada, and CIHR ; has received honoraria from Merck, Bristol-Meyers Squibb, Wyeth, and Pendopharm ; and has served as a adviser on inquiry contracts for Merck, Rebiotix, Acetlion, and Sanofi Pasteur. P. I. T. has received research grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the NIAID, and the Bill & Melinda Gates Foundation. C. W. has received research grants from the NIH, GlaxoSmithKline, and Merck, and served as a adviser for Pfizer and Thera Pharmaceuticals. C. A. W. has received inquiry grants from NIH, NIAID and received a patent from the University of Virginia. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the capacity of the manuscript have been disclosed.

References

For the full list of references, please visit the Oxford University Press web site .

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