Is rifaximin (an antibiotic) effective for primary prophylaxis of Clostridioides difficile (C. diff) infection in high-risk patients?

Rifaximin for Primary Prophylaxis of C. difficile Infection

Rifaximin is NOT recommended for primary prophylaxis of C. difficile infection in high-risk patients, as there is insufficient evidence to support this use. 1

Guideline Recommendations on CDI Prevention

The 2018 IDSA/SHEA guidelines explicitly state there are insufficient data to recommend rifaximin for primary prevention of CDI outside of clinical trials. 1 The guidelines prioritize the following evidence-based prevention strategies instead:

Recommended Prevention Strategies

• Antibiotic stewardship is the cornerstone of CDI prevention, with strong recommendations to minimize the frequency, duration, and number of high-risk antibiotics (particularly fluoroquinolones, clindamycin, and cephalosporins). 1

• Discontinue the inciting antibiotic agent as soon as possible, as this directly influences CDI risk and recurrence rates. 1, 2

• Hand hygiene with soap and water (not alcohol-based sanitizers) is critical, especially during outbreaks, as alcohol does not kill C. difficile spores. 1, 2

• Environmental cleaning with sporicidal agents should be implemented during outbreaks or hyperendemic settings. 1

Why Rifaximin Is Not Recommended for Prophylaxis

The evidence base for rifaximin in CDI is limited to treatment of recurrent infection, not primary prevention:

• Rifaximin has inadequate evidence for treating initial CDI episodes, with the IDSA/SHEA guidelines noting it should not be used as first-line therapy. 1

• Rifaximin has been studied primarily as adjunctive post-vancomycin therapy for patients with multiple recurrences, not as prophylaxis in high-risk patients. 1

• Resistance is a significant concern, with isolates demonstrating high MICs (>256 μg/mL) and development of resistance during treatment well-documented. 1, 3, 4

• Clinical studies report resistance rates ranging from 29.1-48.9% with geographical variance in rifaximin-resistant C. difficile strains. 4

Alternative Prophylactic Considerations

Probiotics: Limited Role

• Probiotics are not recommended for primary CDI prevention outside clinical trials according to IDSA/SHEA guidelines. 1

• However, the 2019 WSES guidelines suggest specific probiotic strains (Saccharomyces boulardii I-745, Lactobacillus casei DN114001, and certain Lactobacillus mixtures) may be considered during high-risk periods such as outbreaks, but only in immunocompetent patients. 1

• Probiotics are contraindicated in immunocompromised patients due to rare but serious risk of bacteremia or fungemia. 1

Proton Pump Inhibitors

• While there is an epidemiologic association between PPI use and CDI, there is insufficient evidence to recommend discontinuing PPIs specifically for CDI prevention. 1

• Unnecessary PPIs should always be discontinued as part of general stewardship. 1

Clinical Pitfalls to Avoid

• Do not use rifaximin prophylactically based on its efficacy in treating recurrent CDI—the mechanisms and evidence base are entirely different. 1

• Avoid empirical CDI treatment unless there is strong clinical suspicion, as unnecessary antibiotic exposure increases resistance risk. 1

• Do not perform test-of-cure after CDI treatment, as PCR can remain positive for weeks due to colonization, leading to unnecessary isolation and treatment. 2