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Tufts OpenCourseware
Author: Sherwood L. Gorbach, M.D.
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1. Mechanisms

Microorganisms that cause diarrhea attack specific areas of the intestine (Table 1). The upper small bowel is the site of attack by bacteria that produce toxins, such as Vibrio cholerae, E. coli and toxigenic food-poisoning bacteria (Staphylococcus aureus and Clostridium perfringens). Viruses such as Rotavirus and Norwalk Agent cause their greatest damage at this site as well. The large intestine is affected by bacteria that invade the bowel mucosa, such as Shigella and Campylobacter. The lower ileum is attacked preferentially by Salmonella and Yersinia.

As a rule organisms that involve the upper small intestine produce fluid and electrolyte loss leading to dehydration; fever and systemic signs of infection are often absent. On the other hand, large bowel pathogens cause fever, abdominal pain and bloody, mucoid, low-volume diarrheal stools.

2. E.coli diarrhea pathogens

Five types of E. coli have been recognized as pathogens in the intestinal tract. Each causes diarrhea by different mechanism, involving a distinct set of virulence factors and genetic elements.

2.1. Enteropathogenic E. coli (EPEC)

attach to the intestinal mucosa, causing diarrhea in children and adults. The precise mechanism of fluid and electrolyte loss is still somewhat controversial. Conventional toxins or invasive mechanisms have not been identified. Subtle changes in the microvillus surface have been noted in association with attached EPEC, and this damage may cause diarrhea.

2.2. Enterotoxigenic E. coli (ETEC)

cause diarrhea by elaboration of two toxins, a heat-labile toxin (LT), which resembles cholera toxin, and a heat-stable toxin (ST).

2.3. Enteroinvasive E. coli (EIEC)

produce dysentery and a clinical picture that is indistinguishable from that of Shigella.

2.4. Enterohemorrhagic E. coli (EHEC) (E.coli 0157:H7)

causes a severe colitis with the passage of grossly bloody stools. It has been associated with consumption of hamburgers. These organisms produce a Shiga-like toxin that damages the large bowel mucosa. Besides diarrheal disease this organism may also cause the hemolytic-uremic syndrome (HUS).

2.5. Enteroaggretative (EaggEC)

a newly described pathogen found in many parts of the world, causes disease by attachment of the organism to the small intestine and subsequent damage to the mucosal lining.

3. Fecal leukocytes

A particularly useful technique to establish a presumptive diagnosis in infectious diarrhea is microscopic examination of the stool (see Table 2). Using two drops of Loeffler’s methylene blue mixed with a small amount of stool on a slide, a search for leukocytes and erythrocytes is undertaken. (An experienced observer can do the examination without the stain, thereby looking for protozoa and other parasites on the same slide.) Invasive pathogens such as Shigella and Campylobacter produce a “sea of polys,” easily visible on every coverslip, as well as red blood cells. The toxigenic organisms, viruses and food poisoning bacteria cause a watery stool that harbors very few formed eleme

Certain organisms produce variable findings on microscopic stool examination, depending on the invasive properties of the strain and the degree of colonic involvement. This category includes Salmonella, Yersinia and V. parahaemolyticus.

Pseudomembranous colitis and antibiotic-associated diarrhea, caused by Clostridium difficile, have unpredictable findings with regard to cellular elements in the stool. Most cases show a profusion of sloughed epithelial and red blood cells, but only rare polymorphonuclear leukocytes. An acute exacerbation of ulcerative colitis can produce a great discharge of leukocytes and erythrocytes into the stool, resulting in an exudative microscopic appearance that resembles bacillary dysentery.

While the fecal microscopic examination is neither infallible nor even helpful in all cases, it is cheap and it does yield immediate information that can guide antibiotic therapy, especially in cases of bacillary dysentery.

4. An overview of therapy

The most devastating consequences of acute infectious diarrhea relate to fluid losses. Toxigenic organisms, such as V. cholerae andETEC, can cause severe dehydration. The major aim of treatment is replacement of fluid and electrolytes. The traditional route of administration has been intravenous, but in recent years oral rehydration therapy (ORT) has proven equally effective physiologically and more practical logistically, especially in developing countries. Indeed, ORT is the treatment of choice for mild to moderate diarrhea in both children and adults, and it can be used even in severe diarrhea after some initial parenteral fluid replacement.

Less than one-tenth of patients with acute diarrhea can be treated successfully with antimicrobial drugs . Among the types that should be treated with such drugs are shigellosis, cholera, and C. difficile diarrhea. There are conflicting reports concerning the efficacy of antimicrobial drugs in several important infections, such as those caused by Campylobacter, and insufficient data for infections caused by Yersinia, Aeromonas, vibrios, and several forms of E. coli. The choice of antimicrobial drugs, where they are indicated, is based on in-vitro sensitivity patterns, which are related to geographic prevalence. One group of antimicrobial drugs, that seem to possess broad-spectrum activity against virtually all important diarrhoeal pathogens (except C. difficile) is the fluoroquinolones, including ciprofloxacin. Fluoroquinolone resistance has increased dramatically in recent years, especially in Salmonella and Campylobacter. Resistance in Campylobacter seems to be related to the introduction of fluoroquinolones in commercial poultry production. In general, the burden of proof is on the physician who decides to treat a simple case of diarrhea. In complicated cases, however, the balance may be loaded in favor of treatment.

The first line of therapeutic defense against mild to moderate forms of acute diarrhea is non-specific therapy. Antimotility drugs are particularly useful in providing symptomatic relief. These agents decrease jejunal motor activity, thereby disrupting forward propulsive motility. There is some evidence that the opiates reduce fluid secretion and enhance mucosal absorption. Rectal sphincter tone also increases. The overall effect is to normalize fluid transport, slow transit time, reduce fluid losses, and ameliorate abdominal cramping. The antimotility drugs have proven safe for use in infectious diarrhea, even in Shigella dysentery, although these drugs should not be used when Shigella is suspected. Bismuth subsalicylate is a useful and safe over-the-counter preparation for mild to moderate diarrhea; the salicylate moiety is believed to be the active agent, but bismuth has antibacterial activity which also may be beneficial. In severe forms of acute diarrhea, loperamide is more effective.

Most infectious diarrhea, even with a recognized pathogen, runs a mild, self-limited course; thus neither a stool culture nor specific treatment is required. The algorithm offers help in deciding which patients should be treated symptomatically and which ones require diagnostic studies or specific treatment.

5. Tables

5.1. Table 1 Clinical Features of Diarrheal Diseases

Table 1 Clinical Features of Diarrheal Diseases
Location of Infection
Small Bowel Large Bowel
Pathogens V. cholerae Shigella
Rotavirus Campylobacter
Norwalk virus E. histolytica
Location of pain Midabdomen Lower abdomen, rectum
Volume of stool Large Small
Type of stool Watery Mucoid
Blood in stool Rare Common
Leukocytes in stool Rare Common (except in amebiasis)
Protoscopy Normal Mucosal ulcers; hemorrhage; friable mucos

5.2. Table 2 Fecal Leukocytes in Intestinal Pathogens

Table 2 Fecal Leukocytes in Intestinal Pathogens
Present Shigella
Variable Salmonella
V. parahaemolyticus
C. difficile (antibiotic-associated colitis)
Absent V. cholerae
Norwalk virus
Giardia Iamblia
Entamaeba histolytica
Food poisoning
Staphylococcus aureus
Clostridium perfringens
Bacillus cereus

5.3. Algorithm for diarrhea

Algorithm for Diarrhea

6. Ancillary Material

6.1. Readings

6.1.1. Required

  • Schaechter Texbook, Chapter 57, pages 519-534.