Is there clinical evidence that Saccharomyces boulardii CNCM I‑745 is effective against Clostridioides difficile infection, and are there any other Saccharomyces boulardii strains with comparable efficacy?

Saccharomyces boulardii CNCM I-745 for Clostridioides difficile Infection

Saccharomyces boulardii CNCM I-745 has proven efficacy in preventing recurrent C. difficile infection when combined with standard antibiotic therapy, reducing recurrence rates by approximately 50-70% in patients with at least one prior episode. 1

Evidence for S. boulardii CNCM I-745 Against C. difficile

Prevention of Recurrent CDI (Strongest Evidence)

Two landmark randomized controlled trials specifically evaluated S. boulardii I-745 for preventing CDI recurrence:

• The first trial demonstrated a 26% recurrence rate with S. boulardii versus 45% with placebo when combined with standard antibiotic therapy 1
• The second trial showed even more dramatic results: 17% recurrence rate with S. boulardii (1 g/day) plus high-dose vancomycin (2 g/day) versus 50% with vancomycin and placebo 1
• Critical caveat: The probiotic was ineffective when combined with lower-dose vancomycin (500 mg/day) or metronidazole (1 g/day), indicating that the antibiotic regimen matters 1

Primary Prevention of CDI

• A meta-analysis using strain-specific subgroup analysis found S. boulardii I-745 effective for primary CDI prevention in patients receiving antibiotics 1
• The American Gastroenterological Association reports a 59% reduction in C. difficile-associated diarrhea (RR 0.41; 95% CI 0.22-0.79) when S. boulardii is given with antibiotics 2
• However, the 2018 IDSA/SHEA guidelines note that no probiotic, including S. boulardii, has demonstrated significant and reproducible efficacy in controlled trials for primary prevention, reflecting more conservative interpretation of the same data 1

Mechanism of Action

• S. boulardii CNCM I-745 prevents the antimicrobial-induced increase in fecal cholic acid, a primary bile acid that triggers C. difficile germination and growth 3
• The probiotic disrupts C. difficile biofilm formation by reducing extracellular DNA (eDNA), an essential structural component of the biofilm matrix, which may explain its effect against recurrences 4
• These mechanisms appear strain-specific to CNCM I-745, as they were not observed with the genetically similar S. cerevisiae 4

Comparison with Other S. boulardii Strains

The evidence is exclusively for the CNCM I-745 strain; no other S. boulardii strains have comparable clinical trial data for C. difficile infection. 1

Why Strain Specificity Matters

• Probiotic efficacy is both strain-specific and disease-specific 1, 2
• The two positive RCTs for CDI recurrence prevention specifically used S. boulardii CNCM I-745 1
• Meta-analyses that pool different probiotic strains together are considered methodologically flawed and should be interpreted cautiously 1
• No published trials exist comparing S. boulardii CNCM I-745 to other S. boulardii strains, making equivalency claims impossible 1

Clinical Recommendations Based on Guidelines

For Recurrent CDI (≥1 Prior Episode)

Probiotics for prevention of recurrent CDI may be an effective adjunct to standard antibiotic treatment (vancomycin) in patients with at least one prior episode of CDI (Recommendation 2B). 1

• Administer S. boulardii CNCM I-745 at 1 g/day (approximately 3 × 10¹⁰ CFU) 2
• Combine with high-dose vancomycin (2 g/day), not lower doses or metronidazole 1
• Start at the beginning of antibiotic therapy and continue throughout the entire antibiotic course 2

For Primary Prevention

• Prophylactic probiotics may be considered for inpatients receiving antibiotics during high-risk periods (such as outbreaks) before disease develops (Recommendation 2C) 1
• The 2018 IDSA/SHEA guidelines state there are insufficient data to recommend probiotics for primary prevention outside clinical trials, reflecting ongoing controversy 1

Absolute Contraindications

Probiotics should NOT be used in: 1, 2

• Immunocompromised patients (risk of fungemia)
• Severely debilitated patients
• Patients at risk of bacteremia or fungemia
• Patients with central venous catheters (in the context of critical illness)

Quality of Evidence and Guideline Divergence

• The overall quality of evidence is rated as low to moderate due to heterogeneity in study populations and limited number of trials 1, 2
• The 2019 WSES guidelines are more supportive of S. boulardii use (Recommendation 2B for recurrent CDI) 1
• The 2018 IDSA/SHEA guidelines are more conservative, noting that probiotics "have shown promise" but "none has demonstrated significant and reproducible efficacy" 1
• This divergence reflects different interpretations of the same two positive RCTs and the weight given to mechanistic studies 1

Practical Algorithm for Clinical Use

For patients with first CDI recurrence:

1. Use vancomycin 125 mg four times daily (or fidaxomicin) as primary therapy 1
2. Add S. boulardii CNCM I-745 1 g/day if vancomycin dose is ≥2 g/day 1
3. Verify patient is immunocompetent before starting probiotic 1
4. Continue probiotic throughout entire antibiotic course 2

For patients with ≥2 CDI recurrences:

1. Consider tapered/pulsed vancomycin regimen as primary strategy 1
2. S. boulardii may be added as adjunctive therapy, though evidence is weaker in multiply recurrent disease 1
3. Fecal microbiota transplantation should be considered if multiple antibiotic attempts fail 1