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INTRODUCTION — Diarrheal diseases represent one of the five leading causes of death worldwide and are a particular concern for children younger than five years old in resource-limited settings [1-4]. Among adults in resource-rich settings, diarrhea is often a "nuisance disease" in the healthy individual [5,6].
Most cases of acute diarrhea in adults are of infectious etiology, and most cases resolve with symptomatic treatment alone. When clinicians care for adults with diarrhea, two important decision points are when to perform stool testing and whether to initiate empiric antimicrobial therapy. Our approach to adults with acute diarrhea will be reviewed here and generally focuses on distinguishing those infectious etiologies for which treatment is beneficial from other causes (algorithm 1).
In the United States, expert guidelines on the diagnosis and management of acute diarrhea include guidelines from the Infectious Diseases Society of America  and the American College of Gastroenterology . Links to these and other guidelines can be found elsewhere. (See 'Society guideline links' below.)
The evaluation of persistent and chronic diarrhea, which is often of a noninfectious etiology, and specific causes of acute diarrhea and chronic diarrhea are discussed separately. (See "Epidemiology and causes of acute diarrhea in resource-rich countries" and "Approach to the adult with chronic diarrhea in resource-rich settings".)
Diarrhea in travelers in or returning from resource-limited settings and the approach to diarrhea in residents of resource-limited settings are discussed in detail elsewhere. (See "Travelers' diarrhea: Microbiology, epidemiology, and prevention" and "Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment" and "Approach to the adult with acute diarrhea in resource-limited countries".)
DEFINITIONS — Diarrhea is defined as the passage of loose or watery stools, typically at least three times in a 24-hour period . It reflects increased water content of the stool, whether due to impaired water absorption and/or active water secretion by the bowel.
The following definitions have been suggested according to the duration of symptoms:
●Acute – 14 days or fewer in duration
●Persistent diarrhea – more than 14 but fewer than 30 days in duration
●Chronic – more than 30 days in duration
Invasive diarrhea, or dysentery, is defined as diarrhea with visible blood or mucus, in contrast to watery diarrhea. Dysentery is commonly associated with fever and abdominal pain.
ETIOLOGY — Most cases of acute diarrhea are due to infections and are self-limited. The major causes of acute infectious diarrhea include viruses (norovirus, rotavirus, adenoviruses, astrovirus, and others), bacteria (Salmonella, Campylobacter, Shigella, enterotoxigenic Escherichia coli, Clostridium difficile, and others), and protozoa (Cryptosporidium, Giardia, Cyclospora, Entamoeba, and others) . Taken together, most cases of acute infectious diarrhea are likely viral, as indicated by the observation that stool cultures are positive in only 1.5 to 5.6 percent of cases in most studies . Among those with severe diarrhea, however, bacterial causes are responsible for most cases. As an example, in a study of 173 healthy adults with severe acute community-acquired diarrhea (defined in this study as ≥4 fluid stools per day for more than three days), a bacterial pathogen was identified in 87 percent of cases . Protozoa are less commonly identified as the etiologic agents of acute gastrointestinal illness.
Noninfectious etiologies become more common as the course of the diarrhea persists and becomes chronic. (See "Approach to the adult with chronic diarrhea in resource-rich settings".)
Exact data on the frequency of different causes of acute diarrhea vary according to the definition used, the diagnostic technology available, and the population studied. In addition, the prevalence of an identifiable infectious agent is probably grossly underestimated since many patients do not seek medical attention and testing is often not performed when patients do contact their clinician . (See "Epidemiology and causes of acute diarrhea in resource-rich countries".)
Site of evaluation — Most adults with acute diarrhea do not present to medical care because of the mild or transient nature of the symptoms.
Office evaluation for acute diarrhea is warranted for individuals with persistent fever, bloody diarrhea, severe abdominal pain, symptoms of volume depletion (eg, dark or scant urine, symptoms of orthostasis), or a history of inflammatory bowel disease. Hospitalization may be warranted in the presence of such concerns, in particular if there is a complex medical history of immunosuppression (eg, because of treatment for malignancy, history of transplantation, or advanced HIV infection) or significant vascular or cardiovascular disease.
History — The initial evaluation of patients who present to medical care with acute diarrhea should include a careful history to determine the duration of symptoms, the frequency and characteristics of the stool, and associated symptoms. Additionally, there should be an attempt to elicit evidence of extracellular volume depletion (eg, dark yellow or scant urine, decreased skin turgor, orthostatic hypotension). Questioning about potential exposures, such as food history, residence, occupational exposure, recent and remote travel, pets, and hobbies, can also provide further diagnostic clues. These historical elements can be helpful to suggest the potential causative pathogens, which in turn can inform additional work-up and the decision to use empiric antibiotic therapy. (See 'Stool tests for bacterial pathogens' below and 'Additional testing in specific circumstances' below and 'Empiric antibiotic therapy' below.)
●Character of symptoms – In addition to informing the severity of disease, details on the frequency and nature of the stool can suggest whether the diarrhea is originating in the small or the large bowel, and thus can suggest certain pathogens (table 1). Diarrhea of small bowel origin is typically watery, of large volume, and associated with abdominal cramping, bloating, and gas . Weight loss can occur if diarrhea becomes persistent. Fever is rarely a significant symptom and occult blood or inflammatory cells in the stool are rarely identified. In contrast, diarrhea of large intestinal origin often presents with frequent, regular, small volume, and often painful bowel movements. Fever and bloody or mucoid stools are common, and red blood cells and inflammatory cells can be seen routinely on stool microscopy.
These inflammatory signs associated with large bowel infection (fever, bloody or mucoid stools) suggest invasive bacteria (eg, Salmonella, Shigella, or Campylobacter), enteric viruses (eg, cytomegalovirus [CMV] or adenovirus), Entamoeba histolytica, or a cytotoxic organism such as C. difficile . Visibly bloody acute diarrhea is relatively uncommon and raises the possibility of enterohemorrhagic E. coli (EHEC) (eg, E. coli O157:H7) infection. Other bacterial causes of visibly bloody diarrhea are Shigella, Campylobacter, and Salmonella species. Bloody diarrhea can also reflect noninfectious etiologies such as inflammatory bowel disease or ischemic colitis. (See "Epidemiology and causes of acute diarrhea in resource-rich countries".)
Syndromes that begin with diarrhea but progress to fever and systemic complaints, such as headache and muscle aches, should raise the possibility of other etiologies, including a typhoidal illness (particularly in travelers from resource-limited settings) or infection with Listeria monocytogenes (particularly if a stiff neck is also present or the patient is a pregnant woman).
Other details that can provide clues to the microbiological diagnosis include:
●Food history – Consumption of unpasteurized dairy products, raw or undercooked meat or fish, or organic vitamin preparations may suggest certain pathogens. (See "Differential diagnosis of microbial foodborne disease".)
Although it is often difficult to know which food exposure was the potential source, the timing of symptom onset following exposure to the suspected offending food can be an important clue to the diagnosis (table 2) :
•Within six hours – suggests ingestion of a preformed toxin of Staphylococcus aureus or Bacillus cereus, particularly if nausea and vomiting were the initial symptoms
•At 8 to 16 hours – suggests infection with Clostridium perfringens
•At more than 16 hours – suggests either viral or other bacterial infection (eg, contamination of food with enterotoxigenic or EHEC or other pathogens)
•Exposure to animals (poultry, turtles, petting zoos) has been associated with Salmonella infection.
•Travel to a resource-limited setting increases the risk of bacterial diarrhea and also informs the risk of certain parasitic infections. (See "Travelers' diarrhea: Microbiology, epidemiology, and prevention", section on 'Etiology'.)
•Occupation in daycare centers has been associated with infections with Shigella, Cryptosporidium, and Giardia. Rotavirus is a potential consideration, but in countries that routinely immunize infants against rotavirus, infection due to rotavirus has decreased substantially.
●Medical history – It is also important to ask about recent antibiotic use (as a clue to the presence of C. difficile infection), other medications (such as proton pump inhibitors, which can increase the risk of infectious diarrhea), and to obtain a complete past medical history (eg, to identify an immunocompromised host or the possibility of nosocomial infection). As examples of medical history informing the likelihood of various pathogens, pregnancy increases the risk of listeriosis following consumption of contaminated meat products or unpasteurized dairy products approximately 20-fold, cirrhosis has been associated with Vibrio infection, and hemochromatosis has been associated with Yersinia infection.
Physical examination — The examination focuses on evaluating volume status and identifying complications.
Volume depletion can be suggested by dry mucous membranes, diminished skin turgor, postural or frank reductions in blood pressure, and altered sensorium. These signs can be mild or absent with early hypovolemia. (See "Etiology, clinical manifestations, and diagnosis of volume depletion in adults", section on 'Physical examination'.)
The abdominal examination should evaluate for findings that can suggest ileus or peritonitis, including abdominal distension, pain with gentle percussion, abdominal rigidity, or rebound tenderness. (See "Evaluation of the adult with abdominal pain in the emergency department", section on 'Physical examination'.)
General laboratory tests — Laboratory tests are not routinely warranted for most patients with acute diarrhea. If substantial volume depletion is present (suggested by signs or symptoms such as dark and concentrated urine), a basic metabolic panel should be performed to screen for hypokalemia or renal dysfunction. The complete blood count does not reliably distinguish bacterial etiologies of diarrhea from others but may be helpful in suggesting severe disease or potential complications. A low platelet count may prompt concern for the development of the hemolytic-uremic syndrome, and a leukemoid reaction is consistent with the diagnosis of C. difficile infection. Blood cultures should be obtained in patients with high fevers or who appear systemically ill.
Stool tests for bacterial pathogens
Indications — For most patients who do not have severe illness or high-risk comorbidities, it is reasonable to continue expectant management for several days without microbiologic stool testing (either stool cultures or multiplex molecular panel tests). However, we obtain microbiologic stool testing for patients with acute community-acquired diarrhea and the following features (algorithm 1) [9,14,15]:
•Profuse watery diarrhea with signs of hypovolemia
•Passage of >6 unformed stools per 24 hours
•Severe abdominal pain
•Need for hospitalization
●Other signs or symptoms concerning for inflammatory diarrhea
•Passage of many small volume stools containing blood and mucus
•Temperature ≥38.5ºC (101.3ºF)
●High-risk host features
•Age ≥70 years
•Comorbidities, such as cardiac disease, which may be exacerbated by hypovolemia or rapid infusion of fluid
•Immunocompromising condition (including advanced HIV infection)
•Inflammatory bowel disease
●Symptoms persisting for more than one week
●Public health concerns (eg, diarrheal illness in food handlers, health care workers, and individuals in day care centers)
The main reason for microbiologic stool testing in patients with acute diarrhea is to identify a potential bacterial pathogen that would inform the potential for complications and treatment decisions. However, most infectious cases of acute diarrhea are self-limited and of viral etiology, and the rate of positive stool cultures in all comers with acute diarrhea is generally low [9,16,17]. Thus, microbiologic stool testing is typically reserved for those patients who are more likely to have a bacterial infection or who would warrant treatment if a bacterial infection were identified, as suggested by the above characteristics.
We typically perform stool cultures for microbiologic stool testing, which can identify the most common bacterial causes of diarrhea. If patients have exposures associated with certain other bacterial pathogens, special culture work-up may be warranted, as below. Many laboratories are adopting multiplex molecular panels to perform microbiologic stool testing. These issues are further discussed below. (See 'Stool culture' below and 'Multipathogen molecular panels' below.)
Routine stool cultures are of little value in patients who develop diarrhea after being hospitalized for 72 hours or more . Testing for C. difficile is much more likely to be helpful . (See "Clostridium difficile infection in adults: Clinical manifestations and diagnosis".)
Stool culture — The optimal specimen for culture is a diarrheal stool specimen, which should be inoculated onto culture plates as quickly as possible. A routine stool culture will identify Salmonella, Campylobacter, and Shigella, the three most common causes of bacterial diarrhea in the United States. E. coli O157:H7 can be isolated on sorbitol-MacConkey plates or identified with antigen testing or polymerase chain reaction of stool (see 'Bloody diarrhea' below). A stool culture that is positive for one of these pathogens in a patient with acute diarrheal symptoms can be interpreted as a true positive.
The clinician may need to specify the bacteria of concern when submitting the stool to facilitate the appropriate processing of the stool in the microbiology laboratory; specific media, methods, or stains may be required to isolate or identify organisms of interest [20-22]:
●Culture for Campylobacter, a fastidious organism, includes collection in transport media and culture on appropriate selective media at a particular temperature and incubation environment; this is routinely done by clinical laboratories.
●When Aeromonas and most strains of Yersinia are possible pathogens (eg, travelers’ diarrhea or foodborne outbreaks, especially in infants), the laboratory needs to be notified; these organisms grow in routine culture but are frequently overlooked unless their isolation is specified.
●Isolation of Vibrio species from stool (suspected in seafood- or shellfish-associated disease, patients with cirrhosis, patients with profuse watery diarrhea, or patients who have traveled to a country with ongoing cholera transmission) generally requires a selective media, such as thiosulfate, citrate, bile salts, and sucrose, to suppress growth of other organisms.
●Gastroenteritis due to Listeria should be considered in outbreaks of febrile gastroenteritis with non-bloody diarrhea if routine cultures are negative.
Performance of stool culture for the various gastrointestinal bacterial pathogens are discussed in the respective topic reviews.
Bacterial pathogens are generally excreted continuously, in contrast to ova and parasites, which are often shed intermittently. Thus, a negative culture is usually not a false negative, and repeat specimens are rarely required.
Multipathogen molecular panels — Some laboratories have access to multiplex stool tests, with which molecular tests for a panel of many different pathogens (bacterial, viral, and parasitic) can be performed simultaneously on diarrheal stool samples and, in some cases, rectal swabs. It is important for clinicians to know which technology is being used for the diagnosis of diarrheal pathogens in their clinical laboratory since performance and result interpretation depend, in part, on the specific test employed.
Furthermore, a high degree of clinical correlation is necessary when interpreting results of molecular testing since these assays detect genetic material, which does not always indicate infection with a viable organism, and identification of more than one pathogen is not uncommon .
Any specimens that test positive for a bacterial pathogen on a multiplex molecular panel (or other culture-independent test) should be submitted for confirmatory culture [7,8]. If the original specimen was a rectal swab, an additional stool specimen may be warranted to perform confirmatory culture. Obtaining an isolate from culture is important for public health purposes and for susceptibility testing.
Additional testing in specific circumstances
Bloody diarrhea — For patients with bloody diarrhea, at least two potential pathogens, EHEC and Entamoeba, warrant additional testing. In addition to culture, we check bloody stools for Shiga toxin and, if available, fecal leukocytes or lactoferrin; if the fecal leukocyte/lactoferrin test is negative, we test for amebiasis. The possibility of noninfectious etiologies may also warrant further evaluation.
●Because of the possibility of EHEC as a cause of bloody diarrhea, such samples should undergo direct testing (with immunoassays or molecular tests) for Shiga toxin. Many laboratories will do this automatically with bloody specimens. Although E. coli O157:H7 can be isolated on sorbitol-MacConkey agar and identified with antigen testing, other strains of Shiga toxin producing E. coli cannot be identified in this way. Many multiplex molecular tests will also test for Shiga toxin as part of the panel. Clinicians should confirm with their clinical laboratory how the Shiga toxin test is performed (so that they can submit the sample optimally) and whether it is automatically performed or requires a specific request. (See "Clinical manifestations, diagnosis and treatment of enterohemorrhagic Escherichia coli (EHEC) infection", section on 'Diagnosis'.)
●Bloody diarrhea can also be caused by intestinal amebiasis, particularly in extended (>1 month) travelers to or migrants from areas of the world where this infection is endemic (India, Africa, Mexico, and parts of Central and South America), men who have sex with men (MSM), or institutionalized individuals. Although the utility of fecal leukocytes in the evaluation of acute diarrhea in general is limited because variability of performance of this test [24-26], the presence of bloody diarrhea in the absence of fecal leukocytes is suggestive of amebiasis, as these organisms destroy leukocytes. The fecal lactoferrin test is an agglutination assay that is also a marker for fecal leukocytes but may have greater accuracy because of fewer issues with user variability . Another biomarker of intestinal inflammation is calprotectin, which serves mostly to determine activity of inflammatory bowel disease but has an uncertain role in infectious diarrhea. When there is bloody diarrhea with few or no fecal leukocytes, stool should be sent for evaluation for amebiasis, which can be diagnosed on stool by microscopy, antigen testing, or molecular methods. (See "Intestinal Entamoeba histolytica amebiasis", section on 'Diagnosis'.)
Noninfectious etiologies, in particular ischemic colitis and inflammatory bowel disease, can also present acutely with abdominal pain and bloody diarrhea. In patients who have risk factors for colonic ischemia, imaging with computed tomography and potentially endoscopy may be warranted. Endoscopy can be useful to evaluate patients with bloody diarrhea for inflammatory bowel disease if their symptoms do not resolve. (See "Colonic ischemia", section on 'Diagnosis' and "Endoscopic diagnosis of inflammatory bowel disease".)
Persistent diarrhea — Work-up and management for patients with persistent diarrhea or diarrhea that does not respond to empiric treatment includes testing for parasitic organisms and other evaluation for noninfectious processes. (See "Approach to the adult with chronic diarrhea in resource-rich settings", section on 'Evaluation'.)
Sending stool samples for ova and parasite testing is not cost effective for the majority of patients with acute diarrhea . However, testing for parasitic organisms is reasonable in patients with persistent diarrhea, among whom parasites become more likely pathogens . The spectrum of parasites associated with persistent diarrhea can vary based on exposures or populations. In general, Giardia, Cryptosporidium, and E. histolytica are the most common parasitic pathogens in patients with persistent diarrhea. Persistent diarrhea following travel to certain locations, such as Russia, Nepal, or mountainous regions, is associated with Giardia, Cryptosporidium, or Cyclospora. Persistent diarrhea with exposure to infants in daycare centers has been associated with Giardia and Cryptosporidium. Microsporidium should be a consideration in immunocompromised patients with persistent diarrhea.
Most of these pathogens can be diagnosed by microscopy for ova and parasites. Three specimens should be sent on consecutive days (or each specimen separated by at least 24 hours) for ova and parasite examination since parasite excretion may be intermittent. Routine microscopy does not detect cryptosporidia spores; if suspected, the laboratory should be alerted to the potential diagnosis, and specific stains (eg, modified acid fast or trichrome stains) for the organisms should be requested. Giardia, Cryptosporidium, and Entamoeba can also be detected by antigen or molecular testing. (See "Approach to stool microscopy" and "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Epidemiology, clinical manifestations, and diagnosis of cryptosporidiosis", section on 'Diagnosis' and "Intestinal Entamoeba histolytica amebiasis", section on 'Diagnosis' and "Cyclospora infection", section on 'Diagnosis'.)
Noninfectious etiologies also become more likely when acute diarrhea persists or does not respond to empiric therapy. The evaluation of patients for a noninfectious etiology should be pursued in those patients in whom evaluation fails to identify a pathogen (eg, bacterial, viral, or protozoal) and the diarrhea worsens or becomes chronic. In some cases, this will include endoscopy, for example, to distinguish inflammatory bowel disease from infectious diarrhea. (See "Approach to the adult with chronic diarrhea in resource-rich settings" and "Endoscopic diagnosis of inflammatory bowel disease".)
Antibiotic or health care exposures — For patients who are currently taking antibiotics, who have taken antibiotics within the past three months, or who have been hospitalized within the past three months prior to presentation with diarrhea, C. difficile colitis is a primary concern. The approach to diagnosis of C. difficile in patients with clinically significant diarrhea is discussed elsewhere. (See "Clostridium difficile infection in adults: Clinical manifestations and diagnosis", section on 'Overview of diagnostic approach'.)
Immunocompromised patients — Although the typical gastrointestinal pathogens are common causative organisms in immunocompromised patients with acute diarrhea, such patients have a higher risk of infections with less common gastrointestinal pathogens, in particular parasites and CMV. The likelihood of particular pathogens depends, in part, on the type of immune compromise. Noninfectious etiologies (eg, medications, graft versus host disease in stem cell transplant recipients) are also considerations. (See "Overview of infections following hematopoietic cell transplantation" and "Infection in the solid organ transplant recipient".)
For patients with acute diarrhea who have advanced HIV infection (CD4 cell count <200 cells/microL or other AIDS-defining condition) or other immunocompromising conditions, stool should be sent for culture as well as parasitic testing (microscopy for ova and parasites with special staining). This is discussed in detail elsewhere. (See "Evaluation of the HIV-infected patient with diarrhea".)
For patients who have concern for possible CMV infection (eg, HIV patients with CD4 cell count <50 cells/microL, transplant recipients), endoscopy with biopsy is the best diagnostic approach. (See "AIDS-related cytomegalovirus gastrointestinal disease", section on 'Diagnosis and differential diagnosis' and "Approach to the diagnosis of cytomegalovirus infection", section on 'Gastrointestinal disease'.)
Neutropenic enterocolitis in patients with severe neutropenia (absolute neutrophil count <500 cells/microL) can present with diarrhea in addition to fever and abdominal pain. Imaging with computed tomography is warranted in such settings. (See "Neutropenic enterocolitis (typhlitis)".)
Outbreak settings — In the setting of a known community outbreak, additional testing may be warranted if patients with potential exposures present with diarrhea. As an example, community waterborne outbreaks or fecal-oral outbreaks have been associated with Giardia, Cryptosporidium, and norovirus, so testing for these parasitic and viral infections is appropriate in such settings. The evaluation of a waterborne outbreak requires a multidisciplinary approach for control. Any outbreak may require reporting of cases to the health department. (See "Approach to stool microscopy", section on 'Clinical approach' and "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Epidemiology, clinical manifestations, and diagnosis of cryptosporidiosis", section on 'Diagnosis' and "Norovirus", section on 'Diagnosis'.)
Men who have sex with men — Receptive anal or oral-anal intercourse increases the risk of direct inoculation or fecal-oral transmission of bacterial and parasitic pathogens (in particular, Shigella, Giardia or E. histolytica). In addition to culture, stool from such patients should also be submitted for parasitic testing. These organisms can be detected by microscopy for ova and parasites (three specimens on consecutive days), by antigen testing, and by molecular methods. There are several nonpathogenic Entamoeba species (Entamoeba dispar, Entamoeba hartmanni, Entamoeba coli) that may be difficult to distinguish from E. histolytica and that may also be sexually transmitted in MSM. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Intestinal Entamoeba histolytica amebiasis", section on 'Diagnosis'.)
Acute diarrhea in MSM can also be a manifestation of proctitis, which can be caused by sexually transmitted infections (chlamydia, gonorrhea, syphilis, herpes simplex virus). Anoscopy can identify anorectal discharge or rectal mucosal friability, which are suggestive of proctitis. Testing for these sexually transmitted infections and empiric treatment for chlamydia and gonorrhea may be warranted in addition to stool culture. (See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections", section on 'Proctitis' and "Treatment of Chlamydia trachomatis infection", section on 'Proctitis'.)
Indications for imaging — Abdominal imaging is not typically warranted in patients with acute diarrhea. However, for patients who have significant peritoneal signs or ileus, abdominal imaging (most typically computed tomography) can be important to identify potential complications, such as bowel perforation, abscess, fulminant colitis, toxic megacolon, or intestinal obstruction. (See "Evaluation of the adult with abdominal pain in the emergency department", section on 'Computed tomography scan'.)
MANAGEMENT — The management of patients with acute diarrhea begins with general measures such as fluid repletion and nutrition maintenance, with adjustments in diet if necessary. Patients who have bothersome symptoms may benefit from symptomatic pharmacologic therapy. Antibiotic therapy is not indicated in most cases since the illness is usually self-limited. Nevertheless, empiric and specific antibiotic therapy may be appropriate in certain situations, mainly in patients with severe disease, with symptoms and signs suggestive of invasive bacterial infection, or at high risk for complications (algorithm 1).
Fluid repletion — The most critical therapy in diarrheal illness is rehydration, preferably by the oral route, with solutions that contain water, salt, and sugar [29-33]. Diluted fruit juices and flavored soft drinks along with saltine crackers and broths or soups may meet the fluid and salt needs in patients with mild illness . The electrolyte concentrations of fluids used for sweat replacement (eg, Gatorade) are not equivalent to oral rehydration solutions, although they may be sufficient for the otherwise healthy patient with diarrhea who is not hypovolemic.
Oral rehydration solutions (ORS), including standard World Health Organization ORS or commercial ORS, such as Rehydralyte and Ceralyte, may be more appropriate in patients with more severe diarrheal disease. They should be used both to replete a volume depleted patient and also to maintain adequate volume status once replete. Composition of available ORS are discussed elsewhere. (See "Oral rehydration therapy", section on 'Commercial and standard ORS' and "Oral rehydration therapy", section on 'ORS properties'.)
ORSs were developed following the realization that, in many small bowel diarrheal illnesses, intestinal glucose absorption via sodium-glucose cotransport remains intact. Thus, in diarrheal disease caused by any organism that depends on small bowel secretory processes, the intestine remains able to absorb water if glucose and salt are also present to assist in the transport of water from the intestinal lumen. Oral rehydration therapy is grossly underutilized in the US where health care providers tend to overuse intravenous hydration.
Adults with severe hypovolemia should initially receive intravenous fluid repletion. Once they are replete, they can be switched to oral rehydration solutions. (See "Maintenance and replacement fluid therapy in adults".)
Dietary recommendations — The benefit of specific dietary recommendations other than oral hydration has not been well established in controlled trials. However, adequate nutrition during an episode of acute diarrhea is important to facilitate enterocyte renewal ; if patients are anorectic or have nausea and vomiting, a short period of consuming only liquids will not be harmful. Boiled starches and cereals (eg, potatoes, noodles, rice, wheat, and oat) with salt are indicated in patients with watery diarrhea; crackers, bananas, soup, and boiled vegetables may also be consumed . Foods with high fat content should be avoided until the gut function returns to normal after a severe bout of diarrhea.
Dairy products (except yogurt) may be difficult to digest in the presence of diarrheal disease. This is due to secondary lactose malabsorption, which is common following infectious enteritis and may last for several weeks to months. Thus, temporary avoidance of lactose-containing foods is reasonable. (See "Lactose intolerance: Clinical manifestations, diagnosis, and management".)
Empiric antibiotic therapy — Given the lack of rapid diagnostic testing methods for enteric pathogens, most decisions on antibiotic therapy are often made empirically at the time of presentation. Indications and agent selection for empiric antibiotic therapy are discussed below.
Indications — We do not routinely use empiric antibiotics in adults with acute diarrhea. Despite their efficacy in reducing the duration of diarrheal symptoms in some settings [9,11,34-36], in most individuals with acute diarrhea, which is usually short-lived and caused by viruses, this benefit does not outweigh the drawbacks of potential side effects, promotion of bacterial resistance, eradication of normal flora (and increased risk of C. difficile infection), and cost. (See 'Efficacy' below.)
However, for select patients with more symptomatic disease or with risk for more severe disease, empiric antibiotic treatment is appropriate, as symptom reduction may have a greater relative benefit in such patients (algorithm 1) . Specifically, we often use empiric antibiotics in the following circumstances:
●Severe disease (fever, more than six stools per day, volume depletion warranting hospitalization)
●Features suggestive of invasive bacterial infection, such as bloody or mucoid stools (except in cases of nonsevere disease when fever is low or absent)
●Host factors that increase the risk for complications, including age >70 years old and comorbidities such as cardiac disease and immunocompromising conditions
The approach to empiric antibiotic treatment of individuals with travelers' diarrhea is discussed elsewhere. (See "Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment", section on 'Antibiotics'.)
Many clinicians are concerned about treating patients with grossly bloody diarrhea given the possibility of enterohemorrhagic E. coli (EHEC) as the causative pathogen. Although we do not use antibiotics for confirmed EHEC infections because there is no evidence of benefit and there is a risk of precipitating hemolytic-uremic syndrome (HUS) with antibiotic therapy , most cases of bloody diarrhea are not caused by EHEC and the association between HUS and antibiotics has predominantly been reported among children. Thus, for most adults with highly symptomatic or severe bloody diarrhea, the benefits of antibiotic therapy likely outweigh the low risk of potential complications from treating EHEC. It is reasonable to withhold empiric antibiotic therapy pending stool testing to rule out EHEC or Shiga toxin production in stable patients when the likelihood of EHEC is higher (eg, bloody diarrhea in the setting of an outbreak or in an afebrile patient). The association between EHEC and HUS is discussed elsewhere. (See "Clinical manifestations, diagnosis and treatment of enterohemorrhagic Escherichia coli (EHEC) infection" and "Clinical manifestations, diagnosis and treatment of enterohemorrhagic Escherichia coli (EHEC) infection", section on 'Role of antibiotics'.)
Choice of agent — When the decision to treat acute diarrhea has been made, we generally use an oral fluoroquinolone (ciprofloxacin 500 mg twice daily, levofloxacin 500 mg once daily, or norfloxacin 400 mg twice daily [not available in the US]) for three to five days [9,11,15,34,36]. Azithromycin (500 mg PO once daily for three days) or erythromycin (500 mg PO twice daily for five days) are alternative agents  for patients who cannot take fluoroquinolones or who are suspected to be at risk for a fluoroquinolone-resistant pathogen (eg, in patients with diarrhea after travel to Southeast Asia, or during outbreaks of resistant pathogens) . (See "Clinical manifestations, diagnosis, and treatment of Campylobacter infection".)
Most studies of empiric treatment of acute diarrhea have evaluated a fluoroquinolone [11,34], and these agents have well-established efficacy in studies of travelers’ diarrhea [39-41]. (See 'Efficacy' below and "Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment", section on 'Selection'.)
Specific circumstances may warrant empiric treatment for other pathogens. These include the following:
●For patients with severe diarrhea in the setting of prior antibiotic therapy, empiric treatment for C. difficile is reasonable if the clinical suspicion is high. (See "Clostridium difficile in adults: Treatment".)
●For pregnant women with diarrhea accompanied by fever or systemic illness who had potential exposure to Listeria monocytogenes, empiric therapy often includes antibiotics with activity against this organism. (See "Treatment, prognosis, and prevention of Listeria monocytogenes infection", section on 'Pregnancy'.)
●For patients with profuse watery diarrhea and potential exposure to cholera (eg, travel to an endemic or epidemic setting), empiric antibiotic coverage of Vibrio cholerae is reasonable given the potential for very severe disease. (See "Overview of cholera", section on 'Antibiotic therapy'.)
Efficacy — In general, empiric therapy for community-acquired acute diarrhea may be beneficial by reducing the duration of symptoms by one to two days [11,34,42], but does not appear to dramatically alter the course of illness in unselected populations.
As an example, in a large Swedish trial, 598 adults with acute diarrhea of less than five days' duration were randomly assigned to norfloxacin 400 mg PO or placebo, each twice daily for five days . Enteric pathogens were isolated in 51 percent of evaluable cases; Campylobacter (29 percent) and Salmonella (16 percent) were the most frequent pathogens. Among all culture-positive patients, norfloxacin modestly reduced time to cure (1.7 versus 2.8 days with placebo), and this benefit was somewhat more pronounced among those classified as being severely ill (1.5 versus 3.4 days with placebo). However, among patients with Salmonella infection, norfloxacin did not decrease time to clinical cure and increased the duration of Salmonella shedding from stool, similar to other studies . (See "Nontyphoidal Salmonella: Gastrointestinal infection and carriage", section on 'Indications'.)
This study was unusual in that enteric pathogens were identified in 51 percent of evaluable cases compared with the usual low rate of pathogen isolation . This was likely related to the majority of participants having had travelers’ diarrhea, as 70 percent had traveled abroad within the previous six weeks.
Other studies of directed treatment of Shigella or Campylobacter diarrheal infections have also suggested faster time to clinical improvement with antibiotic use [44,45]. (See "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic treatment' and "Clinical manifestations, diagnosis, and treatment of Campylobacter infection", section on 'Treatment'.)
Specific antibiotic therapy — Even if a bacterial pathogen is identified, not all patients warrant antimicrobial therapy, and enterohemorrhagic (Shiga toxin producing) E. coli specifically should not be treated with antibiotics. Indications for and selection of antimicrobial therapy for specific intestinal pathogens are discussed in detail in the appropriate topic reviews.
Symptomatic therapy — For patients who want symptomatic therapy, the antimotility agent loperamide (Imodium) can be used cautiously in patients in whom fever is absent or low grade and the stools are not bloody. The dose of loperamide is two tablets (4 mg) initially, then 2 mg after each unformed stool, not to exceed 16 mg/day for ≤2 days. We avoid antimotility agents in patients with clinical features suggestive of dysentery (fever, bloody or mucoid stools) unless antibiotics are also given because of concerns that antimotility agents can prolong disease in such infections or lead to more severe illness. In such patients, bismuth salicylate (Pepto-Bismol, 30 mL or two tablets every 30 minutes for eight doses) is an acceptable alternative, although it is somewhat less effective and there is the potential for salicylate toxicity (especially in those who take aspirin for any reason and pregnant women). Another antisecretory agent, racecadotril, is an effective option for symptomatic therapy, if available (not in the US).
Antimotility agents are effective but should be taken with caution. In several randomized controlled studies, loperamide decreased the number of liquid bowel movements or the time to cessation of diarrhea compared with placebo (generally by approximately one day) [46,47]. The addition of loperamide to antibiotics also decreases the time to symptom resolution compared with antibiotics alone . Diphenoxylate (Lomotil) is an alternative antimotility agent, but it has not been as well studied and may cause central opiate or cholinergic side effects. The dose of diphenoxylate is two tablets (4 mg) four times daily for ≤2 days. Patients should be cautioned that treatment with antimotility agents may mask the amount of fluid lost, since fluid may pool in the intestine. Thus, fluids should be used aggressively when antimotility agents are employed. Furthermore, there continues to be some concern that antimotility agents can prolong the duration of fever, diarrhea, and excretion of the organism in some types of dysenteric illnesses (eg, Shigella) , and so are avoided in such cases.
When compared with placebo, bismuth subsalicylate significantly reduced the number of unformed stools and increased the proportion of patients free of symptoms at the end of treatment trials [50-52]. However, in studies that compared bismuth subsalicylate with loperamide, loperamide brought significantly faster relief [50,53,54]. A role for bismuth subsalicylate may be in patients with significant fever and dysentery, conditions in which loperamide should be avoided. If used, the total dose of bismuth salicylate should be monitored, especially in pregnant women, to prevent salicylate toxicity.
If available, racecadotril, an enkephalinase inhibitor, has been demonstrated in several studies to reduce the output and duration of diarrhea, and in some studies, leads to more rapid improvement with fewer adverse effects compared with loperamide [55-57].
Probiotics — Probiotics with beneficial bacteria that assist in maintaining or recolonizing the intestine with nonpathogenic flora can also be used as alternative therapy. Many different probiotics are available, and each probiotic has different activity, so only specific probiotics may be useful. Lactobacillus GG has been shown to decrease duration of childhood infectious diarrhea and Saccharomyces boulardii may be effective in decreasing the duration of C. difficile infection. There is little value in taking probiotics at the same time as antibiotics. (See "Probiotics for gastrointestinal diseases", section on 'Infectious diarrhea' and "Clostridium difficile and probiotics", section on 'Choice of probiotic agent'.)
FOLLOW-UP — In general, follow-up stool testing is not necessary, even if it was initially positive. In some locations, a negative stool test following infection with certain bacterial infections (eg, Salmonella, Shigella, enterohemorrhagic E. coli) is mandated for occupations with a high risk of transmission (eg, food handling or direct patient care) before returning to work after a diarrheal illness. Clinicians should consult with local public health officials regarding any such requirements.
If diarrhea resolves or responds rapidly to therapy, no further work-up or treatment is necessary. If diarrhea becomes persistent, the search for an etiology should be expanded to try to isolate a treatable process or pathogen or identify a noninfectious etiology. (See 'Persistent diarrhea' above and "Approach to the adult with chronic diarrhea in resource-rich settings".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Acute diarrhea in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Most cases of acute diarrhea are infectious. Overall, most cases of infectious diarrhea are likely viral; however, bacterial causes are responsible for most cases of severe diarrhea. (See 'Etiology' above.)
●Most adults with acute diarrhea do not present to medical care because of the mild or transient nature of the symptoms. For those who present to medical care, the initial evaluation should assess for extracellular volume depletion (eg, dark yellow urine or scant amount of urine, decreased skin turgor, orthostatic hypotension) and determine the duration of symptoms, the frequency and characteristics of the stool, and associated symptoms (eg, fever and peritoneal signs). (See 'History' above and 'Physical examination' above.)
●Inflammatory features (eg, fever, or bloody or mucoid stool) suggest infection of the large bowel, which is associated with pathogens distinct from small bowel infection (table 1). Potential exposures, such as food history, residence, occupational exposure, recent and remote travel, pets, and hobbies, can also provide further diagnostic clues as to potential microbiologic etiology. (See 'History' above.)
●For most patients, it is reasonable to continue expectant management for several days without performing microbiologic stool tests (algorithm 1). However, we obtain standard stool cultures (or multiplex molecular testing, if culture is not available) for patients with acute community-acquired diarrhea and the following features at presentation (see 'Stool tests for bacterial pathogens' above):
•Severe illness (profuse watery diarrhea, signs of hypovolemia, passage of ≥6 unformed stools per 24 hours, severe abdominal pain, need for hospitalization)
•Features of inflammatory diarrhea (bloody diarrhea, small volume mucous stools, fever)
•High-risk host features (eg, age ≥70 years, cardiac disease, immunocompromising condition, inflammatory bowel disease, pregnancy)
•Symptoms persisting for more than one week
•Public health concerns (eg, diarrheal illness in food handlers, health care workers, and individuals in day care centers)
●Further diagnostic testing depends on the presenting features. Grossly bloody diarrhea warrants testing for Shiga toxin (to identify enterohemorrhagic Escherichia coli [EHEC]) and fecal leukocytes or lactoferrin, if available. Testing for Clostridium difficile should be performed in cases of recent antibiotic use or health care exposure. Testing for parasites is not warranted in the majority of patients with acute diarrhea. It is useful, however, in patients with persistent diarrhea, in men who have sex with men, in immunocompromised hosts, during a community waterborne outbreak (associated with Giardia and Cryptosporidium), or with bloody diarrhea with few or no fecal leukocytes (associated with intestinal amebiasis). Parasitic tests include microscopy for ova and parasites as well as antigen or molecular testing for specific organisms. (See 'Additional testing in specific circumstances' above.)
●The most critical therapy in diarrheal illness is volume repletion, preferably by the oral route, with solutions that contain water, salt, and sugar. Adults with severe hypovolemia should initially receive intravenous fluid repletion. Once they are replete, they can be switched to oral rehydration solutions. Adequate nutrition during an episode of acute diarrhea is also important, but a short period of consuming only non-dairy liquids will not be harmful. (See 'Fluid repletion' above and 'Dietary recommendations' above.)
●For most patients with community-acquired, non-travel-associated diarrhea, we recommend not routinely administering empiric antibiotic therapy (algorithm 1) (Grade 1B). Antibiotic therapy can reduce the duration of diarrhea and other symptoms by several days, but potential drawbacks include side effects, promotion of bacterial resistance, eradication of normal flora (and increased susceptibility to C. difficile infection), and cost. The benefit of symptom reduction does not outweigh these drawbacks in most individuals with acute diarrhea, which is usually short-lived and caused by viruses.
•However, for select patients, empiric antibiotic treatment may have a greater relative benefit. We suggest empiric antibiotic therapy for patients with severe disease, features suggestive of invasive bacterial infection (bloody or mucoid stools), or host factors that increase the risk for complications (Grade 2B). (See 'Indications' above.)
For most adults with highly symptomatic or severe bloody diarrhea, the benefits of antibiotic therapy likely outweigh the low risk of potential complications from treating EHEC. It is reasonable to withhold empiric antibiotic therapy pending stool testing to rule out EHEC or Shiga toxin production in stable patients when the likelihood of EHEC is higher (eg, bloody diarrhea in the setting of an outbreak or in an afebrile patient). (See 'Indications' above.)
•For patients in whom empiric antibiotic therapy is warranted, we suggest treatment with a fluoroquinolone (Grade 2B). Fluoroquinolones are given for three to five days. If fluoroquinolones are contraindicated or if fluoroquinolone resistance is suspected (eg, diarrhea after travel to Southeast Asia or during outbreaks of resistant pathogens), azithromycin is an effective alternative. (See 'Choice of agent' above and 'Efficacy' above.)
•Even if a bacterial pathogen is identified, not all patients warrant antimicrobial therapy, and EHEC specifically should not be treated with antibiotics. Indications for and selection of antimicrobial therapy for specific intestinal pathogens are discussed in detail in the appropriate topic reviews. (See "Nontyphoidal Salmonella: Gastrointestinal infection and carriage", section on 'Antimicrobial therapy' and "Shigella infection: Treatment and prevention in adults", section on 'Management' and "Clinical manifestations, diagnosis, and treatment of Campylobacter infection", section on 'Treatment' and "Clinical manifestations, diagnosis and treatment of enterohemorrhagic Escherichia coli (EHEC) infection", section on 'Treatment'.)
●For patients who desire symptomatic therapy, the antimotility agent loperamide can be used cautiously in patients in whom fever is absent or low grade and the stools are not bloody. For patients with clinical features suggestive of dysentery (fever, bloody or mucoid stools), we suggest avoiding antimotility agents unless antibiotics are also given because of concerns of prolonging disease in such infections (Grade 2C). In such patients, bismuth salicylate is an alternative. Racecadotril is another effective antisecretory agent but is not universally available. (See 'Symptomatic therapy' above.)
●The approach to travelers’ diarrhea is discussed in detail elsewhere. (See "Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment".)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Christine A Wanke, MD, who contributed to an earlier version of this topic review.
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