Emergency Medicine

Acute Diarrhea

Which are the major microbial suspects in cases of infectious diarrhea, and which are associated with inflammatory versus noninflammatory conditions? Which drugs are most likely to provoke acute diarrhea? When and how should acute diarrhea be investigated? These and other questions are addressed.

By Abdul Qadir, MD, and Nasir Hussain, MD

How is diarrhea defined and what is its prevalence?

Diarrhea is a deviation from normal bowel movements characterized by an increased frequency or liquidity of stools, or both, often accompanied by an abnormal increase in daily stool weight (more than 200 grams/day). It is classified as acute if onset occurred less than 14 days ago. Diarrhea of greater than 14 days' duration is termed "persistent," and beyond 30 days it is considered chronic.

In the United States, approximately 200 million to 375 million episodes of diarrheal illness occur each year, resulting in approximately 73 million physician visits, 1.8 million hospitalizations, and 3100 deaths.

What are some common and uncommon organisms involved in infectious diarrhea?

There are various clinical settings in which patients are at greater risk than the general population for developing diarrhea. Infants in day care centers are at increased risk for infection from Rotavirus, Giardia lamblia, and Campylobacter species. While HIV/AIDS patients can get atypical infections, they more commonly are infected by the usual pathogens such as Escherichia coli. Cryptosporidiosis, Isospora belli, herpes simplex, Chlamydia trachomatis, Clostridium difficile, and Shigella are some other types of infection causing diarrhea in AIDS patients. Travelers are at risk for enterotoxigenic E. coli, Rotavirus, Salmonella, and Shigella.

When should inflammatory diarrhea be suspected?

Inflammatory diarrhea is suspected when patients present with acute diarrhea accompanied by bloody stools, fever, tenesmus, or abdominal pain. If the inflammation is in the colon, the stool is frequent and small in volume, whereas diarrhea due to small bowel inflammation is usually high in volume. In either case, stool leukocytosis is present, with more leukocytes the more distal the inflammation, as a rule. Infectious causes of inflammatory diarrhea include Salmonella, Shigella, Campylobacter, enterohemorrhagic E. coli, enteroinvasive E. coli, C. difficile, Entamoeba histolytica, and Yersinia. When inflammatory diarrhea is recurrent, noninfectious etiology should be suspected, such as Crohn's disease, ulcerative colitis, and radiation or ischemic colitis.

What are some causes of noninflammatory infectious diarrhea?

Noninflammatory diarrhea is characterized by watery stools that may exceed 1 liter in volume, without associated symptoms suggestive of inflammation. It is caused by bacteria, such as Vibrio cholerae, enterotoxigenic E. coli, and staphylococcal and clostridial food poisoning; viruses, such as Rotavirus and Norwalk agent; and protozoa, such as Cryptosporidium and Giardia. Many of these organisms elaborate enterotoxins and interfere with the absorptive or secretory mechanism of the intestine, resulting in diarrhea.

What are the risk factors for acute infectious diarrhea?

Travelers are at risk for developing infectious diarrhea, most commonly due to enterotoxigenic E. coli as well as to Campylobacter, Shigella, and Salmonella. Visitors to Russia (especially St. Petersburg) may have increased risk of Giardia-associated diarrhea; visitors to Nepal may acquire Cyclospora. Campers, backpackers, and swimmers in wilderness areas may become infected with Giardia.

Diarrhea closely following food consumption at a picnic, banquet, or restaurant may suggest infection with Salmonella, Campylobacter, or Shigella from chicken; enterohemorrhagic E. coli (O157:H7) from undercooked hamburger; Bacillus aureus from fried rice; Staphylococcus aureus or Salmonella from mayonnaise or creams; Salmonella from eggs; and Vibrio species, Salmonella, or acute hepatitis A or B from seafood, especially if raw.

Individuals at risk for infectious diarrhea include those with either primary immunodeficiency (such as IgA deficiency, common variable hypogammaglobulinemia, or chronic granulomatous disease) or the much more common secondary immunodeficiency states (AIDS, senescence, pharmacologic suppression). Common enteropathogens often cause a more severe and protracted diarrheal illness in these individuals. In persons with AIDS particularly, opportunistic infections, such as by Mycobacterium species, certain viruses (cytomegalovirus, adenoviruses, and herpes simplex), and protozoa (Cryptosporidium, Isospora belli, Microsporidia, and Blastocystis hominis) may also play a role. Also in these individuals, agents transmitted venereally through the rectum (such as Neisseria gonorrhoeae, Treponema pallidum, and Chlamydia) may contribute to proctocolitis.

Infections with Shigella, Giardia, Cryptosporidium, Rotavirus, and other agents are very common in day care participants and should be considered.

Infectious diarrhea is one of the most frequent nosocomial infections in many hospitals and long-term care facilities; the causative microorganism varies but is most commonly C. difficile.

What are some medications associated with acute diarrhea?

Although many medications may cause diarrhea, the most frequent offenders include laxatives (lactulose, castor oil, magnesium hydroxide, magnesium citrate), cardiac agents (quinidine), medications for gout (colchicines), diuretics (furosemide, thiazides), toxins (arsenic, organophosphates, insecticides, Amanita phalloides mushroom), diet products (sorbitol, mannitol, diet colas, caffeine, methylxanthine), endocrine agents (as in thyroid replacement), misoprostol, gold, mesalamine, and anticholinesterase inhibitors.

When should acute diarrhea be investigated?

Most cases of acute diarrhea are self-limiting. The cause should be sought in patients who present with profuse diarrhea with dehydration, grossly bloody stools, fever (oral temperature over 101.3°F), passage of more than six unformed stools per day, duration of illness more than 48 hours, or severe abdominal pain, and in any immunocompromised or elderly patient.

What diagnostic studies are used in the evaluation of persistent diarrhea? When should a stool culture be obtained?

The diagnostic workup for acute diarrhea includes measurement of stool volume and white blood cell count, stool cultures for bacterial and viral pathogens, direct stool inspection for ova and parasites, and immunoassays for certain bacterial toxins (C. difficile), viral antigens (Rotavirus), and protozoal antigens (Giardia, E. histolytica).

A stool culture should be obtained in a patient with fever, dysentery, severe diarrhea, or stools that contain leukocytes. Persistent diarrhea is commonly due to Giardia, but additional causative organisms that should be considered include C. difficile (especially if the patient received antibiotics recently), E. histolytica, Cryptosporidium, Campylobacter, and others.

If stool studies are unrevealing, flexible sigmoidoscopy with biopsies and upper endoscopy with duodenal aspirates and biopsies may be indicated.

Is there a role for endoscopy and imaging in acute diarrheal illness?

Structural examination by endoscopy or abdominal imaging may be appropriate in patients with uncharacterized persistent diarrhea. These studies are invaluable to exclude inflammatory bowel disease and as an initial approach if ischemic colitis, diverticulitis, or partial bowel obstruction rather than an infectious etiology is suspected.

Endoscopy becomes useful in cases of acute or persistent diarrhea when the initial clinical and laboratory workup is unrevealing. Flexible sigmoidoscopy may be useful in the patient with signs and symptoms of proctitis (tenesmus, rectal pain, and rectal discharge) or C. difficile colitis, or for identifying noninfectious causes of bloody diarrhea such as inflammatory bowel disease or ischemic colitis.

What is the treatment for acute diarrhea?

Dehydration is a major complication of diarrhea, and in most cases, the only treatment for acute diarrhea is rehydration. Rehydration can be accomplished by an oral rehydration solution (ORS) composed of 3.5 gm sodium chloride, 2.5 gm sodium bicarbonate (or 2.9 gm sodium citrate), 1.5 gm potassium chloride, and 20 gm glucose or 40 gm sucrose per liter of water, as recommended by the World Health Organization. Any pharmacist can prepare this. In many parts of the world, an ORS is readily available as premixed packets, and only water needs to be added. Many home remedies and commercially available rehydration products are also useful in the management of mild acute diarrhea. Some patients may require intravenous rehydration.

Secondary lactose malabsorption is common following infectious enteritis and may last for several weeks to months. Thus, temporary avoidance of lactose-containing foods may be reasonable. The benefit of attempting to repopulate the bowel flora with yogurt containing live cultures or other probiotics is unproven in adults.

When should antimotility agents be used in acute diarrhea?

Depending on the frequency of bowel movements and patient discomfort, antimotility agents may be used to decrease diarrhea frequency. The use of antimotility drugs is contraindicated in cases of bloody diarrhea. Pharmacotherapy with antidiarrheal agents for acute infectious diarrhea can reduce the number of bowel movements and diminish the magnitude of fluid and electrolyte loss. The most commonly used agents include opiates and opiate derivatives (loperamide and diphenoxylate), bismuth subsalicylate, and kaolin-containing agents. Adsorbent agents such as attapulgite and stool texture modifiers are used frequently in over-the-counter medications such as Kaopectate, but their efficacy is uncertain. Bismuth subsalicylate (Pepto-Bismol) is safe and efficacious in the treatment of infectious bacterial diarrhea.

What are the indications for antibiotic therapy?

Most cases of diarrhea resolve spontaneously and do not require treatment with antibiotics. Antibiotic therapy may be considered, however, in the following circumstances:

• for patients presenting with signs and symptoms of bacterial diarrhea such as fever, bloody stools, and the presence of fecal leukocytes or occult blood in the stool;

• to reduce fecal excretion and environmental contamination by a highly infectious agent like Shigella;

• for persistent or life-threatening diarrheal infections such as cholera;

• for traveler's diarrhea, to accelerate resolution of symptoms in individuals who cannot afford to be indisposed by illness; and

• for immunocompromised patients.

Whenever possible, the selection of an antibiotic should be based on culture and sensitivity results. When culture results are not available, empiric treatment with trimethoprim-sulfamethoxazole or a quinolone may be used. Metronidazole should be used when C. difficile colitis or giardiasis is suspected.

What are the features of antibiotic-associated diarrhea? When should pseudomembranous colitis be suspected?

Antibiotic-associated diarrhea is defined as otherwise unexplained diarrhea in association with the administration of antibiotics like ampicillin, amoxicillin, clavulanate, cephalosporin, fluoroquinolones, azithromycin, clarithromycin, erythromycin, and tetracycline.

Possible findings in antibiotic-associated diarrhea range from "nuisance diarrhea" with frequent loose stools and no other complications to colitis with serious potential complications.

Pseudomembranous colitis (PMC) should be suspected in patients with persistent diarrhea following exposure to antimicrobial therapy. Typical features of PMC include watery diarrhea, abdominal cramping, leukocytosis, and fecal leukocytes. In severe cases, hypoalbuminemia and colonic thickening on computed tomography may be present. The most accurate diagnostic test for C. difficile detection is the cytotoxin assay using tissue-cultured cells. The preferred method for most laboratories is enzyme immunoassays (EIA) that detect toxins A and B. Performing EIA on two or three specimens increases the diagnostic yield. Therapy for PMC includes discontinuation of implicated antimicrobial agents, administration of antimicrobial agents directed against C. difficile, and supportive measures. Antimicrobial options include metronidazole and vancomycin.

What are the causative agents for traveler's diarrhea? How can it be managed and what medical advice should be given to international travelers?

Traveler's diarrhea is common during international travel, especially to developing countries. It accounts for 64% of all illnesses affecting tourists. Enterotoxigenic E. coli, Salmonella, Shigella, Cyclospora, and Rotavirus account for most cases. Prevention of traveler's diarrhea includes education regarding risk factors and food and water hygiene. Risk factors include drinking tap water, using ice in drinks, and eating fruit not personally peeled by the traveler or ice cream from a local producer.

Episodes of traveler's diarrhea are nearly always benign and self-limited, but the dehydration that can complicate an episode may be severe and pose a greater health hazard than the illness itself. The most important treatment of traveler's diarrhea is fluid replacement. Antimotility agents may be used to reduce symptom severity. Similarly, antibiotics may be used to limit the severity and duration of illness. Immunosuppressed patients should be considered for prophylaxis for traveler's diarrhea, although this is not currently recommended for most patients. Prophylactic medications include bismuth subsalicylate, antibiotics, and probiotics. Prophylaxis with ciprofloxacin can prevent traveler's diarrhea in 90% of cases. In general, prophylactic antibiotics are effective in preventing most types of diarrheal disease in travelers, but they cannot be recommended unless dehydration or other complications of diarrhea pose such a threat to the particular patient, due to an underlying medical condition, that the benefits of prevention outweigh the risks of antibiotic use. Not only are daily antibiotics costly, but the side effects of sun sensitivity, allergic reactions, altered gastrointestinal flora with colonization by resistant bacteria, yeast infections such as candidal vaginitis, and the small but real risk of C. difficile colitis may exact a medical cost that is unacceptable.

What measures can be employed to prevent acute diarrhea?

Simple steps in personal hygiene and food preparation can prevent diarrheal illness. Handwashing with soap is a simple measure that can be taken by the patient and caregivers.

These steps in hygiene and food preparation are even more important in immunocompromised patients, such as those infected with HIV, cancer chemotherapy recipients, and persons receiving long-term oral steroids or immunosuppressive agents, because they are more susceptible to infection and the resulting illness is more severe.

Alcoholics and persons with chronic liver disease should avoid raw shellfish because their risk of severe infection due to Vibrio is greater. Persons with impaired immune defenses are at increased risk for infection with Listeria monocytogenes from soft French-style cheeses, unheated deli meats, and raw dairy products, and therefore they should avoid these foods. Toxoplasma gondii and L. monocytogenes infections during pregnancy have been associated with miscarriage, so the pregnant patient should avoid high-risk food such as undercooked meats, raw dairy products, soft cheeses, and unheated deli meats.

Among young children and the elderly, illness caused by infection with Salmonella or E. coli can be particularly devastating but is preventable by following safe food practices.

Since typhoid fever in the United States in recent years has often been imported and is potentially severe and largely preventable, immunization with the Vi capsular polysaccharide or Ty21a vaccine (or, only for children under two years old, the heat phenol inactivate) is recommended for travelers to any high-risk environment.