Diphenoxylate

EVIDENCE-BASED ANSWER

Randomized controlled trials have shown that use of quinolone antibiotics for 3 days reduces the length of an episode of travelers' diarrhea (TD) by 1 to 2 days. The disadvantages of antibiotic use in treatment are the incidence of side effects, the prolonged presence of some bacterial pathogens in the stool, and the development of resistant strains. (Grade of recommendation: B, based on published randomized controlled trials in the absence of a systematic review)

RECOMMENDATIONS FROM OTHERS

The United States Centers for Disease Control and Prevention (CDC) state that travelers with nausea, vomiting, cramps, fever, or blood in stools may benefit from treatment for travelers' diarrhea with ciprofloxacin (500 mg twice daily) or trimethoprim-sulfamethoxazole (double-strength tablet twice daily) for 3 days. The CDC also advises use of World Health Organization oral rehydration solution for replacement of lost fluids and salts.[1] The American College of Gastroenterology Practice Parameters Guidelines Committee recommends that travelers bring loperamide and an antimicrobial with them to use in self-therapy of TD.[2] However, neither the CDC nor the American College of Gastroenterology recommend antibiotic prophylaxis for otherwise healthy travelers.[1,2] Dosage and cost information is shown in the Table.

EVIDENCE SUMMARY

Many studies have documented the efficacy of treating TD with antibiotics. Recent studies have emphasized the use of the 4-fluoroquinolones because of the emergence of bacterial resistance against doxycycline and trimethoprim that was found in previous studies of the prophylactic use of antibiotics for TD. Other quinolones besides ciprofloxacin can be expected to be effective; ofloxacin 300 mg twice daily and norfloxacin 400 mg twice daily have been effective in clinical trials.[1] Illness duration can be shortened by 1 to 2.5 days with antibiotic treatment.[3] A review of antibiotic use for TD in The Cochrane Library concluded that antibiotic treatment is associated with a shorter duration of illness at the cost of side effects. Antibiotics increased the proportion of those without diarrhea 72 hours after beginning treatment and also reduced the severity of illness.[4]

Antibiotics should be considered only part of the treatment of TD. Fluid and electrolyte therapy is the first and most important step in treatment and can usually be accomplished through oral rehydration therapy.[5] Nonspecific agents such as bismuth subsalicylate can reduce stool frequency and shorten illness duration as shown in placebo-controlled trials. Antimotility agents such as loperamide (Imodium) and diphenoxylate with atropine (Lomotil) act to slow intraluminal flow of intestinal contents by increasing segmenting contractions in the intestine. Studies show reduced stool frequency and shortened duration of illness. Antimotility drugs should not be used in the setting of febrile dysentery with bloody stools, because such use may prolong or worsen the illness.[2]

Donald C. Spencer, MD University of North Carolina at Chapel Hill (Expert literature search mediated by Joan Nashelsky, MLS.)

CLINICAL COMMENTARY

Most international travelers are well aware of their risk for TD. Many request antibiotic prescriptions before departure, often by phone and at the last minute. Travelers should be aware of food and beverage hygiene, rehydration techniques, adjunctive treatment with bismuth and antimotility agents, and the important difference between antibiotic treatment and antibiotic prophylaxis. Busy practices might consider developing TD patient education media to relieve the time burdens of individual counseling.

Fluoroquinolones have become first-line treatment for TD and are usually well tolerated, though they remain expensive. Trimethoprim-sulfamethoxizole is a good alternative, and doxycycline may be a consideration for sulfa-intolerant patients with limited prescription resources.

Phillip E. Rodgers, MD University of Michigan Ann Arbor

REFERENCES

[1.] Centers for Disease Control and Prevention. Information for health care providers: travelers' diarrhea. Available at: www.cdc.gov/travel/diarrhea.htm. Accessed February 6, 2001.

[2.] DuPont HL. Guidelines on acute infectious diarrhea in adults: the Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 1997; 92:1962-75.

[3.] De Bruyn G. Diarrhoea. Clin Evidence 2000; 4:373-81.

[4.] De Bruyn G, Hahn S, Borwick A. Antibiotic treatment for travellers' diarrhea. The Cochrane database of systematic reviews. Updated May 31, 2000.

[5.] Scarpignato C, Rampal P. Prevention and treatment of traveler's diarrhea: a clinical pharmacological approach. Chemotherapy 1995; 41 (suppl):48-81.

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