Treating Travelers' Diarrhea
Abstract & Commentary
By Philip R. Fischer, MD, DTM&H
Dr. Fischer is Professor of Pediatrics, Department of Pediatric & Adolescent Medicine, Mayo Clinic, Rochester, MN.
Dr. Fischer reports no financial relationships relevant to this field of study.
Synopsis: In conjunction with oral hydration, medications can help decrease the degree and duration of symptoms in patients with travelers' diarrhea. The combination of loperamide and an antibiotic is particularly effective. Either a fluoroquinolone or azithromycin may be used.
Source: Drugs for travelers' diarrhea. The Medical Letter 2008;50 (issue 1291): 58-59.
Travelers' diarrhea is usually a self-limited illness caused by noninvasive enterotoxigenic Escherichia coli. Antimicrobial therapy, in conjunction with adequate oral hydration, can decrease the frequency and duration of excessive stooling. For traveling adults and older children with mild diarrhea, loperamide, a synthetic anti-motility opioid agent, may be administered for one to two days. For travelers with moderate to severe diarrhea, diarrhea lasting more than three days, bloody diarrhea, or fever, an antibiotic is usually recommended. A fluoroquinolone (ciprofloxacin, levofloxacin, norfloxacin, or ofloxacin) is generally given as the first choice for non-pregnant, non-pediatric travelers. Azithromycin is an alternative choice that actually has some advantages over fluoroquinolones. Rifaximin is approved for afebrile travelers older than 12 years of age with noninvasive E. coli and no blood present in the stool.
Up to 40% of travelers experience bothersome diarrhea, and even short-term trips may be significantly compromised by this common illness. The Medical Letter, in its usual clear, concise, practical way, gives direct guidance about the use of medications in patients with travelers' diarrhea. Nonetheless, some questions remain.
At what point should presumptive therapy with antibiotics be started? The guidelines suggest that "mild" diarrhea be treated with loperamide and that an antibiotic be given for "moderate to severe," persistent, febrile, or bloody diarrhea. For many travelers, the practical definition of "severity" depends more on their itinerary, schedule, mode of transportation, and their awareness that even physically mild diarrhea would significantly interrupt their plans. Some travel medicine practitioners would substitute "significantly bothersome" as the criteria by which a traveler would choose to begin antibiotic therapy.
Usually, the uses of loperamide and antibiotics are not mutually exclusive. Data from adults in Mexico1 and from military personnel in Turkey2 suggest that combination therapy is more effective than antibiotic therapy alone. Loperamide, however, should be avoided in young children and in individuals with invasive disease, as suggested by the presence of either blood in the diarrhea or fever.
Which antibiotic should be available for presumptive treatment of travelers' diarrhea? The new Medical Letter guidelines suggest that a fluoroquinolone is still the first choice—except for pediatric and pregnant travelers—but wisely acknowledge that an alternative, azithromycin, does have advantages. Azithromycin seems equally effective to fluoroquinolones in treating E. coli, and azithromycin offers the advantage of also covering other microbes, such as fluoroquinolone-resistant Campy-lobacter, that account for some cases of travelers' diarrhea. If there is reasonable certainty that an individual adolescent or adult traveler's symptoms are due to E. coli, another option would be treatment with rifaximin.
How long should the antibiotic be given? There are data suggesting that a single initial dose of either a fluoroquinolone or azithromycin is as effective as the previously utilized three-day dosing. For azithromycin, however, it is not yet known whether a standard single dose of 500 mg is as effective as the studied single dose of 1000 mg.
What if the treatment is incompletely effective? In that case, one must be cognizant of other microbial causes of diarrhea in travelers. Campylobacter is increasingly resistant to fluoroquinolones. Multi-drug-resistant enteroaggregative E. coli might be a problem in some cases of travelers' diarrhea.3 In addition, seemingly prolonged travelers' diarrhea actually could be due to a subsequent bout of Clostridium difficile diarrhea complicating initially treated E. coli diarrhea.4 Also, parasites such as Cryptosporidium account for about one-tenth as much travelers' diarrhea as enterotoxigenic E. coli.5 Clinicians must consider these other possibilities, and other specific treatments, in the case of travelers' diarrhea that continues despite standard antibiotic therapy.
What would be better than presumptive treatment? An effective vaccine. Unfortunately, even though there is some efficay of current cholera vaccines against enterotoxigenic E. coli,6 this protection is incomplete. Other vaccines are being evaluated.7
- Ericsson CD, DuPont HL, Okhuysen PC, et al. Loperamide plus azithromycin more effectively treats travelers' diarrhea in Mexico than azithromycin alone. J Travel Med 2007;14:312-319.
- Sanders JW, Frenck RW, Putnam SD, et al. Azithromycin and loperamide are comparable to levofloxacin and loperamide for the treatment of traveler's diarrhea in United States military personnel in Turkey. Clin Infect Dis 2007;45:294-301.
- Oundo JO, Kariuki SM, Boga HI, et al. High incidence of enteroaggregative Escherichia coli among food handlers in three areas of Kenya: A possible transmission route of travelers' diarrhea. J Travel Med 2008;15:31-38.
- Norman FF, Perez-Molina J, Perez de Ayala A, et al. Clostridium difficile-associated diarrhea after antibiotic treatment of traveler's diarrhea. Clin Infect Dis 2008;46:1060-1063.
- Nair P, Mohamed JA, DuPont HL, et al. Epidemiology of cryptosporidiosis in North American travelers to Mexico. Am J Trop Med Hyg 2008;79:210-214.
- Jelinek T, Kollaritsch H. Vaccination with Dukoral against travelers' diarrhea (ETEC) and cholera. Expert Rev Vaccines 2008;7:561-567.
- Svennerholm AM, Tobias J. Vaccines against enterotoxigenic Escherichia coli. Expert Rev Vaccines 2008;7:795-804.