What is the evidence behind prophylaxis for Clostridioides difficile (C diff) infection?

Evidence for C. difficile Prophylaxis

There is insufficient evidence to recommend probiotics for primary prevention of Clostridioides difficile infection (CDI) outside of clinical trials, though specific probiotic strains may be considered during high-risk periods such as outbreaks. 1

Current Guideline Recommendations

The most recent guidelines from major infectious disease societies provide clear direction regarding CDI prophylaxis:

Probiotics

• The 2018 IDSA/SHEA guidelines explicitly state there are "insufficient data at this time to recommend administration of probiotics for primary prevention of CDI outside of clinical trials" 1
• The 2019 WSES guidelines suggest prophylactic probiotics "may be considered for inpatients receiving antibiotics during high-risk periods (such as outbreaks) before the disease develops" (Recommendation 2C) 1
• Probiotics should not be administered to immunocompromised patients due to risk of bacteremia or fungemia 1

Strain-Specific Efficacy

When considering probiotics, efficacy appears to be strain-specific:

• Four specific probiotic formulations have shown some effectiveness in meta-analyses:
  • Saccharomyces boulardii I-745
  • Lactobacillus casei DN114001
  • Mixture of Lactobacillus acidophilus and Bifidobacterium bifidum
  • Mixture of three Lactobacilli strains (L. acidophilus CL1285, L. casei LBC80R, L. rhamnosus CLR2) 1
• One strain (L. rhamnosus GG) was found not effective 1

Primary Prevention Strategies

The most strongly supported strategies for CDI prevention include:

1. Antibiotic Stewardship

   • Minimize frequency and duration of high-risk antibiotic therapy 1
   • Discontinue inciting antibiotics as soon as possible 1
   • Target restriction of fluoroquinolones, clindamycin, and cephalosporins based on local epidemiology 1

2. Infection Control Measures

   • Proper hand hygiene (soap and water preferred during outbreaks) 1
   • Private rooms with dedicated toilets for CDI patients 1
   • Environmental cleaning with sporicidal agents 1

3. Proton Pump Inhibitor Management

   • While there is an epidemiologic association between PPI use and CDI, there is insufficient evidence to recommend discontinuation of PPIs specifically for CDI prevention 1
   • However, discontinuation of unnecessary PPIs is warranted as part of general stewardship 1

Limitations of Probiotic Studies

The evidence for probiotics in CDI prevention has significant limitations:

• Studies showing benefit often had unusually high CDI incidence rates in placebo groups (7-20 times higher than expected) 1
• Heterogeneity in probiotic formulations, administration duration, and CDI definitions 1
• Potential risk of probiotic organisms causing infections in hospitalized patients 1, 2
• Quality control issues with commercial probiotic products that may not contain what is listed on the label 2

Special Considerations

For recurrent CDI prevention:

• Probiotics may be an effective adjunct to standard antibiotic treatment (vancomycin) in patients with at least one prior episode of CDI (Recommendation 2B) 1
• Saccharomyces boulardii I-745 has shown some efficacy in preventing recurrence when combined with vancomycin 1

Pitfalls and Caveats

• Avoid probiotics in immunocompromised patients due to risk of bacteremia/fungemia 1
• Careful preparation of Saccharomyces boulardii is needed in ICU settings to prevent cross-contamination to other patients 2
• The efficacy of probiotics is both strain-specific and disease-specific, making generalized recommendations difficult 1
• Meta-analyses may be misleading if they pool different types of probiotics together 1

In conclusion, while specific probiotic strains show promise in certain contexts, current high-quality guidelines do not support routine use of probiotics for primary CDI prophylaxis. Antibiotic stewardship remains the cornerstone of CDI prevention.