Rifaximin to Control Travelers’ Diarrhea
abstract & commentary
By Malcolm Robinson, MD, FACP, FACG
Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City, OK
Disclosure; Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speaker’s bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca,and Centocor.
Synopsis: Rifaximin, a newly released nonabsorbed antibiotic, appears to safely and effectively prevent the onset and substantial morbidity of travelers’ diarrhea.
Source: Herbert L, et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers’ diarrhea. Ann Intern Med. 2005;142:805-812.
Travelers’ diarrhea (td) is common and produces considerable morbidity; 50 million travelers to underdeveloped areas have TD incidence ranging from 30-50%. Enterotoxigenic Escherichia coli (ETC) is the usual cause of TD. Conventional absorbed antibiotics have been used to prevent and treat TD. These are costly, have noxious side effects, and promote resistant organisms.
Rifaximin, a nonabsorbed GI antibiotic, is
approved for treatment of TD due to ETC, but efficacy for TD prophylaxis had been unknown. Rifaximin 200
mg daily, b.i.d., or t.i.d. or placebo doses were given to 210 healthy adult students within 72 hours of arrival in
Guadalajara, Mexico (all received t.i.d. dosing using these regimens with matching dummy drugs as
required). These regimens were administered continuously for 2 weeks. It was hypothesized that t.i.d. therapy would be ideal, partly based on efficacy of t.i.d. bismuth TD prophylaxis. Patients developing TD despite drugs given during the blinded study were treated with azithromycin or levofloxacin. Diarrhea was defined as ³ 3 stools/day with abdominal pain/cramps and/or nausea ± vomiting and/or fever and/or fecal urgency, etc. Groups were also assessed for the occurrence of mild diarrhea and for any moderate to severe enteric symptoms (in the absence of full-scale travelers’ diarrhea).
On rifaximin once daily, 12% of recipients developed TD vs 19% with b.i.d. dosing vs. 13% with t.i.d. administration. Overall, TD rate was 14.7% with rifaximin (all doses) vs 53.7% with placebo. 5.56% of placebo recipients developed bloody stools vs none with rifaximin. Although TD due to invasive bacterial species and pathogens other than enterotoxigenic E. coli was relatively rare, rifaximin seemed protective
against these pathogens as well. Interestingly, rifaximin also protected recipients against mild diarrhea
and other enteric symptoms beyond its marked impact on clearcut TD. Oddly, mutant resistant bacterial
species do not seem to arise as a result of rifaximin therapy. There have been data to suggest that post--
infectious irritable bowel syndrome may be averted by use of this drug.
Commentary
This article provides compelling support for use of rifaximin for prophylaxis of TD. However, as pointed out in an accompanying editorial by Dr.
Gorbach,1 there are many cogent arguments against any form of TD prophylaxis. First, there are good
symptomatic treatments for TD such as loperamide and bismuth subsalicylate. Second, it is wise to avert
TD by judicious avoidance of contaminated foods and drinks. If TD occurs, usual antibiotics or
rifaximin can be used. Nonetheless, there are a number of instances that would favor prophylaxis such as
intercurrent chronic disease, previous severe TD, and many other personal considerations. Despite the
current use of b.i.d. rifaximin, the data described above make a case for use of a single daily dose for TD
prophylaxis. In my view, we will be hearing a lot more about rifaximin, a product with promising potential uses in a number of therapeutic areas including prophylaxis of recurrent diverticulitis in certain patients, primary or adjunctive therapy of inflammatory bowel disease, treatment of small bowel bacterial overgrowth, and possibly management of hepatic encephalopathy (none of these are currently approved indications). Stay tuned.
Reference
1. Sherwood L. et al. How to Hit the Runs for Fifty Million Travelers at Risk. Ann Intern Med. 2005;142:861-862.
By Malcolm Robinson, MD, FACP, FACG Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City, OK Disclosure; Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speakers bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca,and Centocor. Synopsis: Rifaximin, a newly released nonabsorbed antibiotic, appears to safely and effectively prevent the onset and substantial morbidity of travelers diarrhea.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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