Journal Article

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

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

2017

Overview

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 (MIC 50 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.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Adult / Aged / Aged, 80 and over / Anti-Bacterial Agents - administration & dosage / Anti-Infective Agents - administration & dosage / Antibiotics / Biochemistry / Clinical significance / Diarrhea / Diarrhea - diagnosis / Diarrhea - drug therapy / Double-Blind Method / Drug resistance in microorganisms / Drug Resistance, Microbial - drug effects / Drug Resistance, Microbial - physiology / Feces - microbiology / Female / Gastroenterology / Hepatology / Humans / Irritable bowel syndrome / Irritable Bowel Syndrome - diagnosis / Irritable Bowel Syndrome - drug therapy / Male / Medicine / Medicine & Public Health / Microbial Sensitivity Tests - methods / Middle Aged / NCT / NCT01543178 / Neomycin / Oncology / Original / Original Article / Prospective Studies / Rifampin / Rifamycins - administration & dosage / Rifaximin / Transplant Surgery / Young Adult