Pharmocology Update

Rifaximin: Another Choice for Treatment of Travelers’ Diarrhea

By Stan Deresinski, MD, FACP

Rifaximin (Xifaxan™) has rreceived US FDA approval on May 25, 2004, for the treatment of travelers’ diarrhea caused by enteropathogenic (non-invasive) Eschericiha coli in individuals at least 12 years of age. Rifaximin is a rifamycin that is poorly absorbed (< 0.4%) from the gastrointestinal tract, and thus achieves very high concentrations in the feces. It is active in vitro against enterotoxigenic and enteroaggregative E. coli, Shigella spp., and Salmonella spp., as well as against Vibrio cholerae.1-2 Its activity against Campylobacter jejuni is limited.

In a randomized, double-blind placebo-controlled trial in patients with travelers’ diarrhea, rifaximin administration was associated with a reduction of the median time to the last unformed stool, from 60 hours to 32.5 hours.4 Rifaximin shortened the duration of travelers’ diarrhea due to enteroaggregative E. coli from 72 hours in placebo recipients to 22 hours.3 In a blinded, randomized comparison to ciprofloxacin therapy, the median time to resolution of diarrhea was 25.7 hours in the rifaximin group and 25 hours in the ciprofloxacin group.5 Clinical trial data, however, suggest that rifaximin is ineffective in the treatment of shigellosis and campylobacteriosis, both of which are invasive infections.

Rifaximin appears to be well tolerated, although hypersensitivity reactions may occur. Adminstered in high doses, it is teratogenic in animals. Pharmacokinetic drug interactions have not been identified.

The recommended dose is one 200 mg tablet 3 times daily for 3 days. It should not be used in individuals with fever or blood in their stools. The cost is comparable to other recommended antibacterial regimens for treatment of travelers’ diarrhea.

References

1. Sierra JM, et al. In Vitro Activity of Rifaximin Against Eteropathogens Producing Traveler’s Diarrhea. Antimicrob Agents Chemother. 2001;45:643-644.

2. Scrascia M, et al. Susceptibility to Rifaximin of Vibrio cholerae Strains from Different Geographical Areas. J Antimicrob Chemother. 2003;52:303-305.

3. Steffen R, et al. Therapy of Travelers’ Diarrhea With Rifaximin on Various Continents. Am J Gastroenterol. 2003;98:1073-1078.

4. Infante RM, et al. Enteroaggregative Escherichia coli Diarrhea in Travelers: Response to Rifaximin Therapy. Clin Gasttroenterol Hepatol. 2004;2:135-138.

5. Dupont HL, et al. Rifaximin vs Ciprofloxacin for the Treatment of Traveler’s Diarrhea: A Randomized, Double-Blind Clinical Trial. Clin Infect Dis. 2001;33: 1807-1815.

Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.