Bacterial Causes of Diarrhea
Special Feature
Bacterial Causes of Diarrhea
By Richard A. Harrigan, MD, FACEP
Diarrheas of bacteriologic etiology stand out as a group of diseases that may require special tests and may benefit from antimicrobial therapy. Bacterial diarrhea is a type of inflammatory diarrhea, wherein the colon is the principal site of disease, and the organisms generally cause enteroinvasive pathology. The differential diagnosis of inflammatory diarrhea goes beyond non-infectious causes of diarrhea to include such entities as bowel ischemia, inflammatory bowel disease, and radiation-induced colitis. Non-inflammatory diarrhea includes diseases caused by viruses, toxin-producing organisms, parasitic disease, and foodborne organisms; it usually features involvement of the small bowel.1,2 Whereas inflammatory diarrheas usually present with frequent, small-volume stools, noninflammatory disease features frequent, large-volume stools and, thus, may be more likely to present with dehydration issues. Fever and signs of systemic illness and toxicity are more characteristic of inflammatory diarrheal illness; abdominal pain and cramping can be seen with either but tend to be more severe in inflammatory cases.1,2 Tenesmus reflects a colonic process and can be seen with inflammatory disease. The history, or documented presence, of blood or pus in the stool supports a diagnosis of an inflammatory diarrhea, although the absence of fecal leukocytes does not rule-out a bacterial cause.1-4 Testing the stool for occult blood has been studied as an alternative to microscopic examination for fecal leukocytes as a screening test for inflammatory diarrheal illness; in children, occult blood was more sensitive for invasive bacterial disease than was fecal leukocyte testing.5 The negative predictive values of occult blood for invasive bacterial disease in adults and pediatrics were 87% and 96%, respectively. This result should be generalized with caution to other populations, however, as there was a high incidence of invasive bacterial disease in this population (U.S. travelers to Mexico and Mexican children). If fecal leukocyte testing is done in the ED laboratory, the stool sample should be searched for any pus, which, if evident, should be used for the slide sample. A thin smear should then be placed on the slide, and, after the coverslip is placed, methylene blue should be added sparingly next to the cover slip and allowed to seep under it, so as to faintly stain the stool. I have seen a variety of threshold numbers published as to what is a "positive" number of leukocytes on a fecal stain; it seems that rigid adherence to a criterion number is rather arbitrary and that the result should simply be added, as is, to the other historical and physical examination data when trying to arrive at a diagnosis.
Diarrhea in the patient with HIV disease is a complex issue and is beyond the scope of this discussion. Cryptosporidium, microsporidia, and Mycobacterium avium complex are the most frequently identified causes of chronic diarrhea in patients with AIDS.6 Bacterial enteritis occurs with higher frequency and, at times, greater severity in this population; approximately one-fifth of diarrhea in AIDS patients has been attributed to a bacterial etiology.6
In the general population, stool cultures should be reserved for those cases in which a bacterial cause is felt to be likely based on the elements described above. Furthermore, cultures must be ordered with some specificity; most laboratories routinely test only for Salmonella, Shigella, and Campylobacter-other organisms must be specifically requested.2 Specific bacterial agents of diarrhea will be discussed below.
Specific bacterial agents of diarrheal disease
Shigella. Shigellosis is attributable to four major Shigella species-S. sonnei is the most common in the United States and the least virulent.1,2 Transmission is typically fecal-oral but can come from exposure to contaminated food or water.1,2,4 Clinically, patients present with fever, abdominal pain, and copious watery diarrhea that becomes bloody; the abdomen may be tender, especially in the left lower quadrant. Associated seizures are common in children. Other features of the disease include an association with hemolytic-uremic syndrome, toxic megacolon (both usually with S. dysenteriae), and Reiter's syndrome (characteristically with S. flexneri). The disease, especially in its milder forms, may be self-limited, but antibiotics shorten the duration of illness and reduce the rate of relapse.1,2,4,6
Salmonella. Salmonellosis can be divided into non-typhoidal and typhoidal disease. The former is common in the United States, especially in the pediatric population, the elderly, and in certain predisposed individuals (e.g., patients with sickle cell disease, certain malignancies, achlorhydria, ulcerative colitis, steroid dependence, and AIDS);7 it is the most common bacterial enteritis found in AIDS patients.6 Nontyphoidal disease is caused by numerous serotypes; transmission is via exposure to contaminated water or food-classically, poultry, eggs, meat, and milk products.1,2,4 Acute gastroenteritis, which is the most common manifestation of nontyphoidal salmonellosis, features prodromal symptoms of headache, fever, malaise, nausea, vomiting, and abdominal pain, followed by the appearance of diarrhea in minutes to hours. The stools may or may not be bloody. The disease may be self-limited, and antibiotic therapy is generally discouraged in the healthy individual due to concerns of prolonging the carrier state and a lack of effect on the duration of illness. Antibiotics are recommended in patients with immunosuppression (including AIDS and sickle cell disease), prosthetic devices, and in patients who appear to be gravely ill. Individuals who are bacteremic are at risk of seeding a variety of body tissues, and localized infection may ensue.1,2,4,6 Toxic megacolon and perforation can occur.2
S. typhi causes typhoid fever, a disease that is rare in the United States; when it does occur, it is often linked to international travel. Lasting approximately four weeks, it begins with a febrile, flu-like phase with respiratory and gastrointestinal symptoms. A paradoxical bradycardia may occur. Hepatosplenomegaly may develop, and "rose spots" may be seen on the skin, usually over the upper, anterior torso. As the disease progresses, the patient appears more ill, the mental status may become cloudy, seizures may occur, and a characteristic "pea soup" diarrhea develops, with bleeding and intestinal perforation possibly developing. In contrast to nontyphoidal salmonellosis, typhoid fever should always be treated with antibiotics.2,4
Campylobacter. Perhaps the most common cause of bacterial diarrhea in the United States, Campylobacter disease is usually due to C. jejuni. Young children and young adults are the most commonly affected; it is usually contracted from contaminated water or unpasteurized milk or milk products, and undercooked poultry and meats. A spectrum of disease exists, from mild, watery diarrhea to bloody, mucoid diarrhea with fever, abdominal pain, and tenesmus. Complications include toxic megacolon, Reiter's syndrome, cholecystitis, and pancreatitis. The disease may follow a mild, self-limited course, making antibiotic therapy unnecessary; toxic presentation or prolonged course merit antibiotic treatment.1,2,4 In AIDS patients, Campylobacter disease may be indistinguishable from Salmonella infection and should be treated with antibiotics; the infection rate of both organisms is higher in AIDS patients than in the general population.6
E. coli. Although a variety of types of this bacterium can cause a spectrum of diarrheal illness, E. coli 0157:H7, an enterohemorrhagic E. coli, is an emerging infection in the United States and is currently under active surveillance by the CDC. It is an important cause of outbreaks of bloody diarrhea and is more likely to affect individuals at the extremes of age. A major source is undercooked ground beef, but E. coli 0157:H7 can be found in other foods and transmitted via person-to-person contact.1,2 A recent epidemiologic study7 found it to be more common in northern latitudes and more likely than other bacterial enteritides to feature the following characteristics: history of bloody diarrhea; visibly bloody stools; no reported fever; abdominal tenderness; and leukocytosis. Sixty-five percent of patients in this study with E. coli 0157:H7 had three or more of these characteristics.7 Complications include hemolytic uremic syndrome (it is the major cause of this entity in American and Canadian children), thrombotic thrombocytopenic purpura, and toxic megacolon.2,7 Antibiotics are not known to be helpful in E. coli 0157:H7 and may be harmful; moreover, they do not prevent hemolytic uremic syndrome.2 Enterotoxigenic E. coli, a major cause of traveler's diarrhea, can be treated with antibiotics; here, the diarrhea is watery.1,2,4,8
Clostridium difficile. C. difficile is the main causative organism linked to antibiotic-associated colitis. It can occur after treatment with virtually any antibiotic but has been classically linked with cephalosporins, ampicillin, and clindamycin. It also can be passed person-to-person, as evidenced by the occurrence of nosocomial outbreaks. Disease onset is usually 4-9 days after initiation of antibiotics.9 The spectrum of disease ranges from asymptomatic carrier, to mild noninflammatory diarrhea, to fulminant disease. Stools are more likely to be semi-formed than watery but may be greenish-colored, or bloody and mucoid.3 Patients can appear quite toxic, with fever, abdominal pain and tenderness, bloody diarrhea, leukocytosis, and hypoalbuminemia; at this point, pseudomembranes have usually formed.1,3,9 Diagnosis is best made by testing for the C. difficile toxin, although the organism can be grown in culture or the pseudomembranes can be visualized on colonoscopy.1,3,9 Complications include shock, cecal perforation, and profound hemorrhage.9 Treatment should almost always include discontinuation of the offending antibiotic; in milder cases, this may be all that is necessary in addition to supportive care. Patients with fever, significant abdominal pain, leukocytosis, or toxic appearance should receive antibiotics promptly. If the offending antibiotic must be continued, this probably can be done as long as the C. difficile is treated with antibiotics and the patient is closely monitored.1,9
Miscellaneous organisms. As with E. coli 0157:H7, the laboratory must be directed to look specifically for the following less-common organisms, as clinical suspicion dictates. Yersinia enterocolitica is more common in Europe than in the United States; it is transmitted via the fecal-oral route, or from contaminated food or water. It has a predilection for the terminal ileum and can present quite similarly to appendicitis, with fever, abdominal pain, right lower quadrant tenderness, and leukocytosis. Diarrhea progresses from watery to bloody in some cases. If bacteremic, the patient may seed numerous other tissues; other complications include bowel gangrene, hemorrhage, and Reiter's syndrome. Antibiotics should be used for the severely ill or immunocompromised.2 Vibrio parahaemolyticus is generally associated with raw or undercooked fish or shellfish and presents with a viral prodrome, followed by abdominal pain and diarrhea, which is typically explosive and watery, yet may be bloody. Antibiotics are reserved for severe cases.1,2 Aeromonas hydrophila presents similarly but is linked to contaminated fresh water exposure.2 International travel, especially to the tropics, should spark consideration of Entamoeba histolytica.2 Patients with a history of anal intercourse and symptoms of proctocolitis should be evaluated for infection with Neisseria gonorrhoeae, chlamydia, and herpes simplex virus.2
Antibiotic therapy
Although antibiotic therapy is often not necessary for these diseases, it should be considered as discussed above. The majority of organisms respond to fluoroquinolones, making this group of antibiotics an attractive choice when the diagnosis is unclear-unless the patient is pregnant or is a child. C. difficile stands out as an exception; it is generally treated with orally-administered metronidazole or vancomycin. In some instances, antibiotics may help (e.g., shigellosis, enterotoxigenic E. coli). Other times, antibiotics may help but will probably not affect the course of disease (e.g., Campylobacter), and, in some instances, they may prove harmful (some cases of nontyphoidal salmonellosis, E. coli 0157:H7). Before initiating treatment, the immune status and level of illness of the patient should be considered, and an attempt should be made to determine which organisms are the most likely pathogens. The reader is referred to other sources for a complete list of antibiotic alternatives.1,2,6,10,11
References
1. Hogan DE. The emergency department approach to diarrhea. Emerg Med Clin North Am 1996;14:673-694.
2. Robinson PK, et al. Infectious diarrheas. In: Taylor MB, ed. Gastrointestinal Emergencies. 2nd ed. Baltimore, MD: Williams and Wilkins; 1997.
3. Manabe YC, et al. Clostridium difficile colitis: An efficient clinical approach to diagnosis. Ann Intern Med 1995;123:835-840.
4. Larson SC. Traveler's diarrhea. Emerg Med Clin North Am 1997;15:179-189.
5. McNeely WS, et al. Occult blood versus fecal leukocytes in the diagnosis of bacterial diarrhea: A study of U.S. travelers to Mexico and Mexican children. Am J Trop Med Hyg 1996;55:430-433.
6. Framm SR, Soave R. Agents of diarrhea. Med Clin North Am 1997;81:427-447.
7. Slutsker L, et al. Escherichia coli 0157:H7 diarrhea in the United States; clinical and epidemiologic features. Ann Intern Med 1997;126:505-513.
8. Farthing MJ. Travelers' diarrhoea. Gut 1994;35:1-4.
9. Fekety R. Antibiotic-associated colitis. In: Mandell GL, et al, eds. Principles and Practice of Infectious Diseases. 3rd ed. New York, NY: Churchill Livingstone; 1995.
10. Anonymous. The choice of antibacterial drugs. Med Lett 1998;40:33-42.
11. Anonymous. Advice for travelers. Med Lett 1998; 40:47-50.
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