Rifaximin Versus Placebo in the Prevention of Travelers' Diarrhea
Rifaximin Versus Placebo in the Prevention of Travelers' Diarrhea
The purpose of this study is to evaluate the effectiveness of poorly absorbed rifaximin in
 the prevention of travelers' diarrhea among U.S. college students in Mexico for five weeks.
This is an investigator-initiated proposal wherein 220 male and female subjects >17 years of
 age from industrialized regions were randomized to receive a poorly absorbed antibiotic,
 rifaximin, in one of three doses at mealtime (when they are exposed to diarrhea-causing
 bacteria), 200 mg once a day, 200 mg twice a day or 200 mg three times a day versus a placebo
 starting on arrival (within the first 72 hours) to Mexico and continuing for two weeks with
 diaries of symptoms recorded for three weeks. Adverse events in the subjects were followed
 for five weeks. If mild diarrhea (1 or 2 unformed stools/24 hours plus an enteric symptom) or
 diarrheal illness (>2 unformed stools/24 hours plus an enteric symptom) developed, subjects
 provided a stool sample to determine cause of illness. Forty subjects provided stool samples
 after 7 days and 14 days treatment to see if their intestinal bacterial flora had developed
 resistance to rifaximin and to see the level of drug achieved. Stool samples from these forty
 subjects were studied for enteric pathogens to look for asymptomatic infection during the
 period of prophylaxis. The stool samples collected were initially processed in our enteric
 laboratories in Guadalajara, Mexico. Specialized tests such as studies of toxigenicity for
 enterotoxigenic E. coli and enteroadherence for enteroaggregative E. coli were done in
 Houston.
Inclusion Criteria:

 -  An Investigational Review Board approved, written informed consent is appropriately
 witnessed, signed and dated prior to any study-related activities

 -  Male or female subjects 18 years of age or older

 -  Able to read and understand English

 -  Enrolled and started on prophylaxis within 72 hours of arrival in Mexico

 -  If the subject is female, only women with non-childbearing potential or those who are
 not pregnant will be eligible. Urine pregnancy tests will be performed on those women
 who question their pregnancy status. Women on the study are required to employ a
 reliable method of contraception while taking medication. Forms of acceptable
 contraception include:

 -  Double barrier method of contraception.

 -  Oral birth control pills for at least two cycles before enrollment and continuing
 during therapy - subjects will be told they should use a barrier contraception
 method during the study as well.

 -  Norplant inserted at least one month before enrollment.

 -  An intrauterine device inserted by a qualified clinician.

 -  Medroxyprogesterone acetate for a minimum of one month before study and
 administered for one month following study completion.

 -  An approved birth control patch for at least two cycles before enrollment and
 continuing during therapy. OR

 -  Complete abstinence from intercourse for the two weeks of medication.

 Exclusion Criteria:

 -  Acute diarrhea (criteria for travelers' diarrhea above) within the past week

 -  Diarrhea developing within 24 hours of study enrollment

 -  In Mexico for more than 72 hours

 -  Receipt of one of the following classes of drugs: fluoroquinolone (any drug in class),
 macrolide or azalide or trimethoprim-sulfamethoxazole within the past week or during
 the three week study

 -  Receipt of other medication to decrease the occurrence of diarrhea (e.g. bismuth
 subsalicylate or lactobacillus preparations)

 -  For females, pregnancy or breast feeding during the three week study

 -  Receipt of antidiarrheal medication (loperamide, bismuth subsalicylate, kaopectate)
 within 24 hours of enrollment

 -  Hypersensitivity to rifaximin

 -  Unstable medical condition including chronic renal failure and insulin dependent
 diabetes.