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A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment
Published on: May 25, 2017
Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic
M Pimentel1, B D Cash2, A Lembo3
1GI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 225E, Los Angeles, CA, 90048, USA. Mark.Pimentel@cshs.org.
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.
Insights
Repeat rifaximin treatment for IBS-D showed no long-term impact on gut bacteria
Area of Science:
- Gastroenterology
- Microbiology
- Pharmacology
Background:
- Rifaximin is an effective and safe treatment for diarrhea-predominant irritable bowel syndrome (IBS-D).
- Understanding the impact of repeat rifaximin treatment on gut microbiota antibiotic susceptibility is crucial for long-term therapeutic strategies.
Purpose of the Study:
- To evaluate the effect of repeat rifaximin treatment courses on the antibiotic susceptibility of fecal bacteria in patients with IBS-D.
Main Methods:
- Patients responding to initial rifaximin treatment in the TARGET 3 study received repeat courses (rifaximin or placebo) in a double-blind phase.
- Stool samples were collected at multiple time points for susceptibility testing against 11 antibiotics, including rifaximin and rifampin.
- Bacterial and yeast isolates were identified, with a focus on common gut bacteria like Bacteroidaceae and Enterobacteriaceae.
Main Results:
- Clostridium difficile and Staphylococcus isolates remained highly susceptible to rifaximin and rifampin throughout the study.
- No long-term cross-resistance was observed in key bacterial groups (Bacteroidaceae, Enterobacteriaceae, Enterococcaceae) to rifampin or other tested antibiotics following rifaximin exposure.
Conclusions:
- Short-term, repeat treatment with rifaximin does not appear to induce long-term changes in the antibiotic susceptibility of the gut microbiota.
- These findings support the continued use of rifaximin for managing IBS-D without significant concerns for developing antibiotic resistance in the gut microbiome.
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