A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers' diarrhea.

BACKGROUND

Travelers' diarrhea causes substantial morbidity and postinfectious irritable bowel syndrome.

OBJECTIVE

To evaluate nonabsorbable rifaximin for prevention of travelers' diarrhea.

DESIGN

Randomized, double-blind, placebo-controlled clinical trial.

SETTING

Guadalajara, Mexico.

PARTICIPANTS

U.S. students.

INTERVENTION

On arrival in Guadalajara, Mexico, 210 U.S. adults received rifaximin (200 mg/d, 200 mg twice daily, or 200 mg 3 times daily) or placebo for 2 weeks.

MEASUREMENTS

Participants were followed daily for 3 weeks for enteric disease and symptoms and daily for 5 weeks for drug side effects. Changes in intestinal coliform flora were studied.

RESULTS

Travelers' diarrhea developed in 14.74% of participants taking rifaximin and 53.70% of those taking placebo (rate ratio, 0.27 [95% CI, 0.17 to 0.43]). Rifaximin provided 72% and 77% protection against travelers' diarrhea and antibiotic-treated travelers' diarrhea, respectively (P < 0.001 for both), and all rifaximin doses were superior to placebo. In the groups that did not report travelers' diarrhea, rifaximin significantly reduced the occurrence of mild diarrhea (P = 0.02) and moderate and severe intestinal problems (P = 0.009 for pain or cramps; P = 0.02 for excessive gas). Rates of adverse events were comparable in the rifaximin and placebo groups. Minimal changes in coliform flora were found during rifaximin therapy.

LIMITATIONS

Rifaximin safely prevented travelers' diarrhea in Mexico, where most cases are caused by diarrhea-producing Escherichia coli. A study is needed in Asia to determine whether rifaximin can prevent diarrhea caused by invasive bacterial pathogens.

CONCLUSIONS

Rifaximin prevents travelers' diarrhea with minimal changes in fecal flora, and more liberal chemoprophylaxis against this disease should be considered. Future studies should evaluate whether rifaximin is effective in preventing postinfectious irritable bowel syndrome.