Antibiotic Susceptibility of Skin Swab Staphylococcus Isolates From Patients With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Treated With Repeat Courses of Rifaximin Showed No Evidence of Resistance

Abstract

Introduction: Rifaximin, a minimally absorbed antimicrobial derived from rifamycin SV, is approved for the treatment of IBS-D. This exploratory analysis assessed the impact of rifaximin repeat treatment on antibiotic susceptibility of Staphylococcus skin isolates from patients with IBS-D. Methods: Patients with IBS-D in TARGET 3 who responded to open-label rifaximin 550 mg TID for 2 weeks entered a double-blind (DB) randomized phase of the trial if they experienced IBS-D symptom relapse during 18 weeks of follow-up: patients received two, 2-week, repeat courses of rifaximin 550 mg or placebo TID that were separated by 10 weeks. Staphylococcal isolates were cultured from skin swabs collected before and after 2 weeks of open-label rifaximin, before (DB baseline) and after the first 2-week repeat DB treatment (rifaximin or placebo), and at the end of the study (22 weeks after DB baseline). Susceptibility testing, using a broth microdilution method, included 11 antibiotics. Results: Skin swabs were obtained for 115 patients and 31 also participated in the DB phase (rifaximin [n=19]; placebo [n=12]). A total of 1381 isolates (18 strains) were identified, with the majority being of Staphylococcus epidermis (54.2%) or Staphylococcus hominis (17.2%) species. In isolates from patients who relapsed, before randomization to rifaximin or placebo (DB baseline), isolates from placebo group had rifaximin MIC50 (0.015 mcg/mL) and MIC90 (0.03 mcg/mL) values identical to those observed with rifaximin. Rifaximin MIC50 remained low through the end of the study (0.015-0.06 mcg/mL). Transient changes in rifaximin MIC90 were observed in the DB rifaximin group, but not the DB placebo group, with a return to DB baseline MIC90 by the end of the study. Rifampin MIC50 remained low in the DB placebo group (≤0.015 mcg/mL) and the DB rifaximin group (≤0.015-0.03 mcg/mL). Transient changes in rifampin MIC90 were observed in the DB rifaximin group, but not the DB placebo group, with a return to baseline MIC90 by the end of the study. For the other antibiotics tested, regardless of treatment group (open-label rifaximin, DB placebo, or DB rifaximin), MIC changes were minimal and did not indicate resistance development after rifaximin exposure. Conclusion: Up to 3 courses of rifaximin in patients with IBS-D did not result in clinically significant antibiotic resistance in Staphylococcus skin isolates. Importantly, there was no evidence of crossresistance with other antibiotics tested.