Treatment and Prevention of Acute Traveler's Diarrhea

Introduction
Traveler's diarrhea (TD) may be defined as diarrhea that develops while a person is abroad in or shortly after return from a developing country. It affects 20% to 50% of travelers to tropical and semitropical area, including Latin America, parts of the Caribbean, southern Asia, and Africa. It is usually self-limited, with a duration of less than 1 week, and is certainly the most common malady encountered by this group of travelers. In addition to the morbidity, TD exacts a formidable financial toll from both the traveler and the host country in thwarted business plans and lost tourism revenue. Prophylaxis of TD is therefore an important issue and a critical part of pretravel counseling.

Dietary Precautions
Prevention begins with dietary precautions. Travelers are advised specifically to avoid tap water, foods washed on water (such as salads), ice, unpasteurized milk, sauces and salsas, uncooked seafood, and raw or poorly cooked meats. Consuming foods purchased from street vendors carries a particularly high risk of TD. Safe foods and beverages include carbonated bottled beverages; food cooked and serving piping hot; and dry foods, such as bread and cereal.

Bismuth
Bismuth subsalicylate, having been shown to prevent 60% to 65% of cases of TD, may be used as a prophylactic agent. However, bismuth needs to be taken four times daily for full preventive effect and can be associated with tinnitus and blackening of the tongue and stool.

Antimicrobials
Antimicrobials have long been known to reduce the incidence of TD. The efficacy of prophylactic antibiotics is likely explained by the fact that the vast majority of cases of TD (approximately 80%) are caused by bacteria, the most common pathogens being enterotoxigenic Escherichia coli, followed in prevalence by other pathogenic Enterobacteriaceae, especially Campylobacter and noncholera vibrios. However, antimicrobials carry several disadvantages, including potential allergic and photosensitivity reactions, antibiotic-associated diarrhea, candidal vaginitis, and the development of antibiotic resistance. Consequently, they generally should be reserved for travelers with immune compromise or inflammatory bowel disease or for those situations in which TD could have dire medical or social consequences.

While we think that the risk-benefit ratio disfavors the use of antimicrobials for prophylaxis of TD, antimicrobial treatment after the onset of acute TD will generally shorten the course of illness by 2 to 3 days, tipping the ratio in the affirmative direction. Our practice, therefore, has generally been to prescribe a 3-day course of antibiotics to be carried abroad and patient-initiated at the onset of significant diarrhea. A larger quantity may be dispensed if a prolonged sojourn is planned, to be used in the event of repeated episodes of TD.

Quinolones and Macrolides
Quinolones are the antimicrobials most often considered, because of their appropriate antibacterial spectrum, benign side-effect profile, and the effectiveness of short courses. Problems arise with quinolones, however, with respect to contraindications in children and pregnant women and an increasing problem of resistance among Camphylobacter species in Thailand, Nepal, and other locales. Macrolides, such as azithromycin, which tend to be less well tolerated than quinolones, seem to cover these resistant strains and are becoming the drug of choice in these geographic area. Use of trimethoprim-sulfa methoxazole, an earlier mainstay, while carrying the benefits of lower cost and Cyclospora coverage, has become largely obsolete because of widespread resistance, frequent allergic reaction (which can be serious), and drug interactions.

A New Antibiotic
Rifaximin, an essentially nonabsorbed rifamycin derivative that is currently awaiting FDA approval for use in the United States seems to be comparable in effectiveness to quinolones in management of TD and may have a role in prophylaxis as well. It has potent activity against gram-positive, gram-negative, aerobic, and anaerobic pathogens and has a tolerability and safety profile comparable to that of placebo. There is also a lack of association with stable resistance. Rifaximin is likely to be safer than other drugs in children and pregnant women, and no drug interactions have been seen with its use. It represents a new paradigm in managing enteric infections and holds great promise in the sphere of TD prophylaxis, in which systemic side effects and safety concerns have tipped the risk-benefit ratio away from using other antibiotics.

Are Probiotics Helpful?
Probiotics, defined as five microbial food supplements that beneficially affect the host animal by improving the GI microbial balance, have been tested as preventive agents against TD. In small trials involving 50 American travelers to Mexico and British soldiers deployed to Belize, no benefit from Lactobacillus acidophilus, Lactobacillus fermentum, or Lactobacillus bulgaricus was demonstrated in the prevention of TD.

Conclusions
Prevention of TD is an important part of pretravel counseling. Dietary counseling remains the mainstay. Bismuth is a reasonable but convenient option. Antimicrobial prophylaxis is effective, but given its potential side effects, it is recommended for only a handful of patients. For most patients, a prescription for antibiotics to be brought with them and self-administered after the onset of significant diarrhea is one reasonable approach. The application of newer, nonabsorbable, luminally acting antimicrobials, such as rifaximin, and the use of priobiotics of prophylaxis of TD appear promising but await corroboration in clinical trials.