Can Xifaxan (Rifaximin) Be Used for C. diff?
Xifaxan (rifaximin) should NOT be used as initial treatment for C. difficile infection, but it is an effective option for second or subsequent recurrences when used after completing a standard course of vancomycin. 1, 2
Primary Treatment: Not Recommended
Rifaximin is not recommended as monotherapy or first-line treatment for initial C. difficile infection due to insufficient data confirming effectiveness in complicated or severe disease and significant risk of developing resistance. 2
Vancomycin or fidaxomicin remain the preferred first-line treatments for initial CDI episodes. 2, 3
The IDSA/SHEA guidelines explicitly state that rifaximin has inadequate evidence to recommend treatment of an initial CDI episode. 1
Recurrent C. diff: Appropriate Use
For second or subsequent recurrences, rifaximin becomes a viable treatment option with the following specific regimen: 1, 2
Recommended Regimen
Vancomycin 125 mg orally four times daily for 10 days, immediately followed by rifaximin 400 mg three times daily for 20 days. 1, 2
This sequential therapy approach showed that CDI recurrences occurred in only 15% of patients given rifaximin versus 31% given placebo (P = 0.11) in a small randomized controlled trial. 1
Strength of Evidence
The IDSA/SHEA recommendation for rifaximin in recurrent CDI carries a weak recommendation with low-quality evidence. 2
Alternative options for second or subsequent recurrences include vancomycin in a tapered and pulsed regimen, fidaxomicin 200 mg twice daily for 10 days, or fecal microbiota transplantation after at least two recurrences. 2
Critical Caveats and Pitfalls
Resistance Development
Rifaximin resistance is a major concern, with isolates demonstrating high MICs (>256 μg/mL) well documented, and resistance can develop rapidly during treatment. 1
Clinical studies report resistance rates ranging from 29.1-48.9%, with geographical variance in distribution of rifaximin-resistant C. difficile strains. 4
In vivo selection of rifamycin-resistant C. difficile has been documented within 32 hours of receiving rifaximin therapy. 5
Predictors of Response
The MIC value of rifampin appears to predict response to rifaximin treatment, with most responsive isolates having very low MIC values (<0.002 μg/mL). 6
Strains with DNA profiles compatible with the BI/NAP1/027 ribotype tend to have higher MICs of rifampin and may respond less favorably. 6
Pediatric Considerations
In children with second or subsequent recurrences, rifaximin may be used after vancomycin, but there is no established pediatric dosing. 1, 2
Rifaximin is not FDA-approved for use in children <12 years of age. 1
The adult dosage of 400 mg three times daily carries a weak recommendation with very low-quality evidence in pediatric populations. 1, 2
First Recurrence: Not the Right Time
For a first recurrence, rifaximin is not the preferred approach. 1
First recurrence should be treated with oral vancomycin (particularly if metronidazole was used initially), vancomycin in a tapered and pulsed regimen, or fidaxomicin. 1
Metronidazole is not recommended for treatment of recurrent CDI due to lower initial and sustained response rates compared to vancomycin. 1