Acute diarrheal disease accounts for 179 million outpatient visits annually in the United States. Diarrhea can be categorized as inflammatory or noninflammatory, and both types have infectious and noninfectious causes. Infectious noninflammatory diarrhea is often viral in etiology and is the most common presentation; however, bacterial causes are also common and may be related to travel or foodborne illness. History for patients with acute diarrhea should include onset and frequency of symptoms, stool character, a focused review of systems including fever and other symptoms, and evaluation of exposures and risk factors. The physical examination should include evaluation for signs of dehydration, sepsis, or potential surgical processes. Most episodes of acute diarrhea in countries with adequate food and water sanitation are uncomplicated and self-limited, requiring only an initial evaluation and supportive treatment. Additional diagnostic evaluation and management may be warranted when diarrhea is bloody or mucoid or when risk factors are present, including immunocompromise or recent hospitalization. Unless an outbreak is suspected, molecular studies are preferred over traditional stool cultures. In all cases, management begins with replacing water, electrolytes, and nutrients. Oral rehydration is preferred; however, signs of severe dehydration or sepsis warrant intravenous rehydration. Antidiarrheal agents can be symptomatic therapy for acute watery diarrhea and can help decrease inappropriate antibiotic use. Empiric antibiotics are rarely warranted, except in sepsis and some cases of travelers’ or inflammatory diarrhea. Targeted antibiotic therapy may be appropriate following microbiologic stool assessment. Hand hygiene, personal protective equipment, and food and water safety measures are integral to preventing infectious diarrheal illnesses.
Acute diarrheal disease is a common cause of clinic visits and hospitalizations. In the United States, diarrhea accounts for an estimated 179 million outpatient visits, 500,000 hospitalizations, and more than 5,000 deaths annually, resulting in approximately one episode of acute diarrheal illness per person per year.1–5
Consistent recommendation from evidence-based practice guidelines with high-level evidence
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.
Diarrhea is the passage of three or more loose or watery stools in 24 hours.5–7 Acute diarrhea is when symptoms typically last fewer than two weeks; however, some experts define acute as fewer than seven days, with seven to 14 days considered prolonged.2 Diarrhea lasting 14 to 30 days is considered persistent, and chronic diarrhea lasts longer than one month.2,5,7,8
Diarrhea can be categorized as inflammatory or noninflammatory. Inflammatory diarrhea, or dysentery, typically presents with blood or mucus and is often caused by invasive pathogens or processes. Noninflammatory or watery diarrhea is caused by increased water secretion into the intestinal lumen or decreased water reabsorption.2
Differential Diagnosis
Noninflammatory and inflammatory diarrhea may be subsequently categorized into infectious and noninfectious causes (Table 1).2,5,9,10
TABLE 1.
Characteristics of Noninflammatory and Inflammatory Diarrhea
Infectious noninflammatory diarrhea, the most common presentation, is typically viral in etiology, but bacterial causes are also common and are usually related to travel or foodborne illness.9,11,12
Infectious inflammatory diarrhea is more severe and is typically caused by invasive or toxin-producing bacteria, although viral and parasitic causes exist.12 Bloody stools, high fever, significant abdominal pain, or duration longer than three days suggests inflammatory infection. The most identified inflammatory pathogens in North America are Salmonella, Campylobacter, Clostridioides difficile, Shigella, and Shiga toxin–producing Escherichia coli.2,12
Specific pathogenic causes differ based on location, travel or food exposures; work or living circumstances (e.g., health care, long-term care settings); and comorbidities, such as HIV or other immunocompromised states.
Noninfectious causes of diarrhea include dietary intolerance, adverse medication effects, abdominal surgical processes such as appendicitis or mesenteric ischemia, thyroid or other endocrine abnormalities, and gastrointestinal diseases, such as Crohn disease or ulcerative colitis10,12(Table 28,10,12). Although many of these processes are chronic, they can present acutely and should be included in the differential diagnosis of acute diarrhea.
A history for patients with acute diarrhea should include symptom onset, severity (volume, frequency, duration of diarrhea), stool character, and a focused review of systems, including vomiting, fever, decreased urine output, and abdominal pain.9,12
Additional exposure history can help suggest potential etiology and the need for further evaluation. Physicians should ask about recent travel, food or water exposures, known contacts with sick people, occupations, residence, recent medical history (e.g., illnesses, hospitalizations, antibiotics, other medications), and sexual history.2,9,12
Assessing for medical comorbidities, including immunocompromised states or personal or family history of autoimmune conditions, can be useful in identifying patients at high risk of complicated diarrheal illnesses (Table 32,5,9,12–14).
TABLE 3.
Significant Historical Factors for Acute Diarrhea
*—If Escherichia coli O157 or Shiga toxin–producing E. coli, monitor complete blood count and basic metabolic panel for hemolytic uremic syndrome; these pathogens are more commonly found with bloody diarrhea without fever.
†—In patients with AIDS, perform additional testing for Cryptosporidium, Cyclospora, C ystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus.
The initial physical examination should focus on disease severity and hydration status. Clinicians should take note of general appearance, fever, tachycardia, and hypotension. Peripheral pulses, skin turgor, and capillary refill may also assist in assessing volume status. The abdominal examination should evaluate for an acute abdomen requiring potential surgical intervention.2,12,13
Additional Evaluation
Further diagnostic evaluation is indicated for patients with inflammatory diarrhea or severe symptoms, including sepsis, or for those whose history includes risk factors for complications or potential outbreaks (e.g., patients who are immunocompromised, food handlers, health care or child-care workers, and community or nursing home residents).
STOOL TESTING
Most patients who are immunocompetent with acute, nonbloody diarrhea without systemic symptoms do not require stool testing.2,5,6,12,13Stool studies should be obtained in patients with acute bloody diarrhea, fever, severe abdominal pain, signs of sepsis, or duration of seven days or greater, and patients with occupational or residential risk factors for an outbreak. Molecular, or culture-independent studies, also known as multiplex polymerase chain reaction or nucleic acid amplification tests, are generally preferred over traditional stool cultures.2,5,15 These methods allow for rapid detection of bacterial, viral, and parasitic pathogens concurrently. Multiplex testing in inflammatory diarrhea should include Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, and Shiga toxin. Specific exposures and travel history may dictate the need to test for additional pathogens. For example, patients who report swimming in brackish water or consuming undercooked shellfish warrant evaluation for Vibrio species.2
A limitation of molecular testing is that it identifies the presence of an organism but does not indicate clinical significance. Molecular methods are also of limited use in patients whose symptoms are related to an outbreak. If a clinician suspects an outbreak requiring a public health investigation, separate stool cultures are required to assist with reporting.2,5 Nationally reportable causes of death include specific pathogens (i.e., Campylobacter, giardiasis, Listeria monocytogenes, and others), foodborne outbreaks, waterborne outbreaks, and postdiarrheal hemolytic uremic syndrome.2
C. DIFFICILE
Adult patients who were recently hospitalized for more than three days or who used antibiotics within the past 12 weeks should undergo nucleic acid amplification testing or multistep testing for C. difficile. Testing requires a fresh, nonsolid sample. Evaluation and management guidelines for C. difficile can be found in separate updates.14,16
BLOOD TESTING
Blood testing is not routinely recommended for patients with acute diarrhea.12 A chemistry panel evaluating electrolytes and kidney function is appropriate for patients with dehydration. Complete blood count with differential and blood cultures should be obtained in patients with signs of sepsis. Patients with confirmed or suspected E. coli O157 or other Shiga toxin infections are at risk of hemolytic uremic syndrome. A blood cell count and chemistry panels should be obtained in these patients to monitor for changes in hemoglobin, platelets, electrolytes, and kidney function.2
NOT RECOMMENDED
Fecal leukocytes, lactoferrin, and calprotectin are of limited utility and are not recommended in the evaluation of acute infectious diarrhea.2,5,12 Fecal leukocytes break down easily in samples, reducing sensitivity. Fecal lactoferrin is more sensitive and can be associated with severe dehydration and bacterial etiology, but it lacks the specificity to be clinically useful.2,15,17 Fecal calprotectin, a marker of inflammatory bowel disease, has shown associations with bacterial causes for acute diarrhea, including C. difficile, but results lack consistency.2,17 Fecal occult blood testing generally should not be used in the evaluation of diarrhea.18
ENDOSCOPY
Patients with acute diarrhea do not require endoscopic evaluation unless symptoms persist for more than one month and laboratory results are nondiagnostic.5,19
Patients with HIV, AIDS, and other immunocompromised conditions are at greater risk of invasive or opportunistic infections. An endoscopic examination should be considered in patients who are immunocompromised and whose initial stool testing is nondiagnostic or whose diarrhea is functionally disabling.2,20,21
Management
Treatment of acute diarrhea depends on the suspected or determined cause. Supportive therapy with early rehydration and refeeding is recommended regardless of etiology.
REHYDRATION AND REFEEDING
Supportive management begins with replacing water, electrolytes, and nutrients. Oral rehydration is the preferred method for fluid replacement. Severe dehydration associated with shock, sepsis, or altered mental status warrants rehydration with isotonic intravenous fluid.2,5
Oral rehydration solution has decreased the worldwide mortality of acute diarrhea, particularly in children and older people. Oral rehydration has been shown to decrease total stool output, episodes of emesis, and the need for intravenous rehydration, by slowly releasing glucose into the gut to improve salt and water reabsorption.22 Prepackaged oral rehydration solution is available commercially, but similar recipes can be made at home with readily available ingredients (Table 4).23
Reintroducing food as early as tolerated decreases the intestinal permeability caused by infection, reducing illness duration and improving nutritional outcomes. The evidence for a particular refeeding diet is insufficient; therefore, an age-appropriate regular diet is recommended.6,24
ANTIDIARRHEAL MEDICATIONS
The antisecretory properties of bismuth subsalicylates and the antimotility properties of loperamide (Imodium) make these two drugs the most useful symptomatic therapies for acute watery diarrhea and can help decrease inappropriate antibiotic use. A loperamide and simethicone combination has demonstrated faster and more complete relief of acute watery diarrhea and gas-related abdominal discomfort compared with either medication alone.25
In cases of travelers’ diarrhea (TD), adjunct loperamide therapy with antibiotics has been shown to increase the likelihood of a clinical cure at 24 and 48 hours.26
Loperamide and other antimotility agents should be avoided in patients with bloody or suspected inflammatory diarrhea because of the potential for toxic megacolon and prolonged illness. Bismuth subsalicylates are a safe alternative in patients with fever and inflammatory diarrhea.2,5
TABLE 5.
Empiric Antibiotics for Travelers’ Diarrhea
*—Preferred empiric regimen for febrile illness with or without bloody stool or in areas where fluoroquinolone-resistant Campylobacter is common.
†—Avoid when invasive pathogens are suspected.
Adapted with permission from Riddle MS, DuPont HL, Connor BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111(5):610.
TABLE 6.
Targeted Antibiotic Therapy for Infectious Diarrhea With an Identified Pathogen
TMP/SMX = trimethoprim/sulfamethoxazole.
*—Fidaxomicin is more expensive than oral vancomycin but shows less resistance and requires fewer daily doses.
Adapted with permission from Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65(12):e66, with additional information from reference 16.
STANDBY ANTIBIOTICS
Although previous guidelines recommended providing standby antibiotics to most travelers, studies have shown no significant illness reduction with self-treatment and have raised concerns about effects on the gut microbiota and antibiotic resistance. The decision to provide standby antibiotics should be individualized based on the patient’s risk of developing moderate to severe TD.5,29
PROBIOTICS
There are no formal recommendations for or against probiotics to treat acute diarrheal illness due to a lack of consistent evidence. One Cochrane review found that probiotics decrease the mean duration of acute diarrhea by one day and decrease the risk of diarrhea lasting more than four days. Another large meta-analysis found a 15% relative decrease in the risk of TD with prophylactic probiotic use.30,31 Other studies have shown inconclusive or insufficient evidence. The decision to use probiotics should be individualized for the patient and situation.30,31
Prevention
HYGIENE
Adequate handwashing, proper use of personal protective equipment, and food and water safety practices are mainstays for preventing the transmission of diarrheal illness. Proper handwashing with soap and water for at least 20 seconds before rinsing shows the most benefit in reducing transmission of the more contagious pathogens (e.g., Norovirus, Shigella) and should be promoted in settings of community or institutional outbreaks. Patients who are hospitalized, including those with C. difficile colitis, may require contact precautions with appropriate personal protective equipment, including gloves and a gown.
Implementation of guidelines from the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration on food and water safety decreases the risk of foodborne diarrheal illness in the United States; however, the risk increases with travel. Pretravel counseling about high-risk food and beverages can be used to help prevent TD.5,9 A previous article in American Family Physician discussed foodborne illness in more detail.9
VACCINATION
Typhoid and cholera vaccines are recommended for people traveling to endemic areas or with known personal or occupational exposures.2 Vaccines for other diarrhea-causing agents continue to be investigated.
Sequelae
Postinfectious irritable bowel syndrome is a common sequela of acute gastroenteritis, occurring in 4% to 36% of patients depending on the infective pathogen, with a pooled prevalence of 11% in one meta-analysis.32,33 Presenting as unexplained persistent diarrhea in the absence of an infectious agent, postinfectious irritable bowel syndrome is thought to be caused by an inability to downregulate intestinal inflammation following acute bacterial infection. Symptoms may last for months or years and are most common following Campylobacter, Shigella, or Salmonella infection. Effective prevention and treatment of acute bacterial illness decrease the chances of developing postinfectious irritable bowel syndrome.32,33 Potential postinfectious diarrhea sequelae are listed in Table 7.2
Gastrointestinal adverse effects are common in patients with SARS-CoV-2. Symptoms vary among patients with COVID-19, and diarrhea may be the only presenting complaint for some. COVID-19–associated diarrhea is self-limited but may be severe in some patients. The overall clinical significance of COVID-19–associated diarrhea is unclear but causes concern about potential fecal-oral transmission of the virus.34
This article updates a previous article on this topic by Barr and Smith.12
Data Sources: A search was completed using PubMed, EBSCOhost, DynaMed, Essential Evidence Plus, and the Cochrane database. Key terms searched were acute diarrhea, travelers’ diarrhea, acute diarrhea evaluation, acute diarrhea testing, acute diarrhea treatment, diarrhea antibiotics, acute diarrhea prevention, postinfectious diarrhea, and COVID diarrhea. Also searched were the Centers for Disease Control and Prevention and World Health Organization websites. Search dates: August 2021 to January 2022, and April 2022.
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Uniformed Services University of the Health Sciences, the U.S. Army Medical Department, or the U.S. Army at large.
ERICA S. MEISENHEIMER, MD, MBA, FAAFP, is a faculty physician at the National Capital Consortium Family Medicine Residency at Fort Belvoir (Va.) Community Hospital, and an assistant professor in the Department of Family Medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md.
CARLY EPSTEIN, DO, is a chief resident in the Department of Family Medicine at Fort Belvoir Community Hospital.
DERRICK THIEL, MD, MPH, is an adjunct faculty member at the Madigan Army Medical Center Family Medicine Residency, Joint Base Lewis-McChord, Wash., and an assistant professor at the Uniformed Services University of the Health Sciences.
Address correspondence to Erica S. Meisenheimer, MD, MBA, 9300 Dewitt Loop, Fort Belvoir, VA 22060 (email: erica.j.meisenheimer.mil@mail.mil). Reprints are not available from the authors.
Author disclosure: No relevant financial relationships.
