A Randomized, Double-Blind, Placebo-Controlled Trial of Rifaximin To Prevent Travelers' Diarrhea

17 May 2005 | Volume 142 Issue 10 | Pages 805-812

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.

Editors' Notes Context Using absorbed antibiotics to prevent travelers' diarrhea is costly, has side effects, and promotes resistant organisms. Rifaximin is a nonabsorbed antibiotic approved for treating travelers' diarrhea. Its effectiveness in preventing the condition is unknown. Contribution In this randomized trial, 210 adults who were newly arrived in Guadalajara, Mexico, took 1 of 3 dosages of rifaximin or placebo for 2 weeks. The rate of travelers' diarrhea was 53.70% in the placebo group and 14.74% in the treated groups. Treatment caused minimal changes in fecal flora. Cautions It is uncertain whether these findings are generalizable to geographic areas where Escherichia coli is not the major pathogen. –The Editors

 

Author and Article Information

From the University of Texas–Houston, Baylor College of Medicine, St. Luke's Episcopal Hospital, and M.D. Anderson Cancer Center, Houston, Texas; and Hospital General de Occidente and Universidad Autonoma de Guadalajara, Guadalajara, Mexico.

Trial NCT00098384.

Presented at Digestive Diseases Week, New Orleans, Louisiana, 16 May 2004.

Acknowledgments: The authors acknowledge the valuable contributions of several colleagues. The field research team was composed of Dorothy Ruelas, RN; Sylvia Vaca, RN; Carmen Pulido; Mathew Cherno; David Hamilton; Elizabeth Juarez; Shelby Melton; Sean Pawlowski; and Courtney Ramirez. Directors of the participating schools at the Guadalajara Summer Programs of the University of Arizona and the University of San Diego were Drs. Macario Saldate and Carl Jubran. Robert Haake and Mary Sarah Baraniuk provided statistical advice on the study, and Dr. David N. Taylor provided editorial help.

Grant Support: By Salix Pharmaceuticals; the Vaccine and Treatment Evaluation Unit Enteric Challenge Studies (NO1-AI-25465); and Public Health Service grant DK 56338, which funds the Texas Gulf Coast Digestive Diseases Center.

Potential Financial Conflicts of Interest: Consultancies: H.L. DuPont (Salix Pharmaceuticals), P.C. Okhuysen (Abbott Laboratories, Aventis, Bristol-Myers Squibb, Cubist, Merck, Pfizer, Salix Pharmaceuticals, Trimeris), C.D. Ericsson (Salix Pharmaceuticals); Honoraria: H.L. DuPont (Salix Pharmaceuticals), P.C. Okhuysen (Abbott Laboratories, Aventis, Bristol-Myers Squibb, Cubist, Merck, Pfizer, Salix Pharmaceuticals, Trimeris), C.D. Ericsson (Salix Pharmaceuticals); Grants received: H.L. DuPont (Salix Pharmaceuticals), C.D. Ericsson (Salix Pharmaceuticals).

Requests for Single Reprints: Herbert L. DuPont, MD, 6720 Bertner Avenue, MC 1-164, Houston, TX 77030; e-mail, hdupont{at}sleh.com.

Current Author Addresses: Dr. DuPont: 6720 Bertner Avenue, MC 1-164, Houston, TX 77030.

Dr. Jiang: University of Texas–Houston School of Public Health, 1200 Herman Pressler, Houston, TX 77030.

Dr. Okhuysen: Division of Infectious Diseases, University of Texas– Houston Health Science Center, 6431 Fannin Street, JFB 1.728, Houston, TX 77030.

Dr. Ericsson: University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77050.

Dr. de la Cabada: Avenida "C", 630K, Col. Seattle Zapopan, Jalisco CP 45150, Mexico.

Dr. Ke: University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Ms. DuPont: 1111 Herman Drive, 19F, Houston, TX 77004.

Dr. Martinez-Sandoval: Universidad Autonoma de Guadalajara, Apartado Postal 1-440, Guadalajara, Jalisco 45110, Mexico.

Author Contributions: Conception and design: H.L. DuPont, Z.-D. Jiang, C.D. Ericsson, S. Ke, F. Martinez-Sandoval.

Analysis and interpretation of the data: H.L DuPont, Z.-D. Jiang, P.C. Okhuysen, C.D. Ericsson, S. Ke.

Drafting of the article: H.L. DuPont.

Critical revision of the article for important intellectual content: H.L. DuPont, Z.-D. Jiang, P.C. Okhuysen, C.D. Ericsson, S. Ke.

Final approval of the article: H.L. DuPont, Z.-D. Jiang.

Provision of study materials or patients: H.L. DuPont, P.C. Okhuysen, C.D. Ericsson, F.J. de la Cabada, F. Martinez-Sandoval.

Statistical expertise: H.L. DuPont, Z.-D. Jiang, S. Ke.

Obtaining of funding: H.L. DuPont.

Administrative, technical, or logistic support: H.L. DuPont, Z.-D. Jiang, P.C. Okhuysen, C.D. Ericsson, M.W. DuPont.

Collection and assembly of data: H.L. DuPont, Z.-D. Jiang, P.C. Okhuysen, F.J. de la Cabada, M.W. DuPont, F. Martinez-Sandoval.