Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity

M Pimentel, B D Cash, A Lembo, R A Wolf, R J Israel, P Schoenfeld, M Pimentel, B D Cash, A Lembo, R A Wolf, R J Israel, P Schoenfeld

Abstract

Background: Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D).

Aim: To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility.

Methods: Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods.

Results: Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (n = 37) or placebo (n = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008-1 µg/mL] and rifampin (MIC range 0.004-0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC50 range ≤0.06-32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested.

Conclusions: In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. CLINICALTRIALS.

Gov identifier: NCT01543178.

Keywords: Diarrhea; Irritable bowel syndrome; Microbiology; Rifaximin.

Conflict of interest statement

Conflict of interest

M. Pimentel reports serving as a consultant for and receiving research funding from Salix Pharmaceuticals. In addition, Cedars-Sinai Medical Center has a licensing agreement with Salix Pharmaceuticals. B.D. Cash reports serving as a speaker, consultant, and an advisory board member for Salix Pharmaceuticals. A. Lembo reports serving as a consultant and an advisory board member for Salix Pharmaceuticals, Ironwood Pharmaceuticals, Inc., Allergan plc, Ardelyx, and Valeant Pharmaceuticals. R.A. Wolf is a former employee of Salix Pharmaceuticals. R.J. Israel is an employee of Salix Pharmaceuticals or its affiliates. P. Schoenfeld reports serving as a consultant and advisory board member for Salix Pharmaceuticals, Ironwood Pharmaceuticals, Allergan, and Commonwealth Laboratories, a division of Valeant Pharmaceuticals North America LLC.

Ethical standards

All procedures performed in the study were in accordance with the International Standard of Good Clinical Practice procedures and with the principles of the Declaration of Helsinki (1964) and relevant amendments. The protocol was approved by all institutional review boards and ethics committees at participating sites.

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