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.


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


METHODS
Guadalajara, Mexico.


METHODS
U.S. students.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
DuPont
Herbert L
HL
University of Texas-Houston, Baylor College of Medicine, St. Luke's Episcopal Hospital, and M.D. Anderson Cancer Center, Houston, Texas 77030, USA. hdupont@sleh.com
Jiang
Zhi-Dong
ZD
Okhuysen
Pablo C
PC
Ericsson
Charles D
CD
de la Cabada
Francisco Javier
FJ
Ke
Shi
S
DuPont
Margaret W
MW
Martinez-Sandoval
Francisco
F
D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D003967:Diarrhea / Q000382:microbiology / Q000517:prevention & control*; D004311:Double-Blind Method; D004927:Escherichia coli Infections / Q000517:prevention & control*; D006801:Humans; D007408:Intestinal Absorption; D008800:Mexico; D010919:Placebos; D011446:Prospective Studies; D012294:Rifamycins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000078262:Rifaximin; D014195:Travel; D016896:Treatment Outcome; D014481:United States
D000900:Anti-Bacterial Agents; D010919:Placebos; D012294:Rifamycins; D000078262:Rifaximin