Should probiotics be given to prevent Clostridioides difficile (C. diff) infection?

Probiotics for Prevention of C. difficile Infection

For patients at high risk of developing C. difficile infection who are receiving antibiotics, specific probiotic strains should be used for prevention, including Saccharomyces boulardii, the 2-strain combination of L. acidophilus CL1285 and L. casei LBC80R, the 3-strain combination of L. acidophilus, L. delbrueckii subsp bulgaricus, and B. bifidum, or the 4-strain combination of L. acidophilus, L. delbrueckii subsp bulgaricus, B. bifidum, and S. salivarius subsp thermophilus. 1

Evidence for Probiotics in C. difficile Prevention

The American Gastroenterological Association (AGA) provides a conditional recommendation with low quality evidence supporting the use of specific probiotic strains for C. difficile infection (CDI) prevention in adults and children receiving antibiotic treatment 1. This recommendation is particularly applicable to high-risk populations.

Effective Probiotic Strains

Based on the AGA guidelines, the following specific probiotics have demonstrated efficacy in preventing CDI:

• Saccharomyces boulardii (RR 0.41; 95% CI, 0.22-0.79)
• 2-strain combination: L. acidophilus CL1285 and L. casei LBC80R (RR 0.22; 95% CI, 0.11-0.42)
• 3-strain combination: L. acidophilus, L. delbrueckii subsp bulgaricus, and B. bifidum (RR 0.35; 95% CI, 0.15-0.85)
• 4-strain combination: L. acidophilus, L. delbrueckii subsp bulgaricus, B. bifidum, and S. salivarius subsp thermophilus (RR 0.28; 95% CI, 0.11-0.67) 1

Risk Stratification for Probiotic Use

The benefit of probiotics varies significantly based on baseline risk:

• High-risk patients (>5% baseline risk of CDI): Greatest benefit observed, with approximately 70% risk reduction 2
• Moderate to low-risk patients (≤5% baseline risk): Limited or no significant benefit 2

High-risk factors for CDI include:

• Hospitalized patients
• Elderly patients
• Prolonged antibiotic use
• Previous history of CDI
• Immunocompromised status (though probiotics should be used with caution in this group)

Implementation Algorithm

1. Assess patient risk for CDI

   • Determine if patient is receiving antibiotics
   • Evaluate baseline risk factors (hospitalization, age, prior CDI)

2. For high-risk patients receiving antibiotics:

   • Initiate one of the recommended probiotic formulations
   • Begin probiotics as close as possible to antibiotic initiation
   • Continue throughout antibiotic course

3. For moderate to low-risk outpatients:

   • Consider individual risk-benefit ratio
   • May reasonably select no probiotics given limited benefit 1

4. Contraindications:

   • Severely immunocompromised patients
   • Patients at risk of bacteremia or fungemia 1

Important Caveats and Considerations

• Quality of evidence: The overall quality of evidence supporting probiotic use for CDI prevention is low 1
• Strain specificity: Efficacy is strain-specific; not all probiotics are effective 1
• Timing matters: Probiotics should be administered close to the time of antibiotic administration for maximum effectiveness 3
• Safety profile: Short-term use of probiotics appears generally safe when used alongside antibiotics in immunocompetent patients 1
• Cost considerations: Patients who place high value on avoiding associated costs and have low risk of CDI may reasonably choose not to use probiotics 1

Treatment vs. Prevention

It's important to distinguish between prevention and treatment of CDI:

• For prevention of CDI in antibiotic recipients: Specific probiotics are recommended as outlined above
• For treatment of established CDI: There is insufficient evidence to recommend probiotics; they should only be used in the context of clinical trials 1

The World Society of Emergency Surgery (WSES) guidelines also support limited use of probiotics as an adjunctive treatment to antibiotics for immunocompetent patients with a first episode of CDI, though this is a weaker recommendation (2B) 1.

Conclusion

When deciding whether to use probiotics for CDI prevention, the key determinant should be the patient's baseline risk for developing CDI. For high-risk patients receiving antibiotics, specific probiotic strains have demonstrated meaningful reductions in CDI risk and should be considered as preventive therapy.