What is the evidence‑based recommendation for using Saccharomyces boulardii (Florastor) as adjunct therapy in adult Clostridioides difficile infection, including dosing, duration, and contraindications?

Evidence-Based Practice for Saccharomyces boulardii (Florastor) in Clostridioides difficile Infection

For recurrent CDI, add Saccharomyces boulardii CNCM I-745 1 g/day to high-dose vancomycin (≥2 g/day) to reduce recurrence by approximately 50-70%; do not use for initial CDI episodes or in immunocompromised patients. 1

Clinical Indications

Recurrent CDI (≥1 Prior Episode)

• S. boulardii is effective only for recurrent CDI, not initial episodes. 2 In patients with at least one prior CDI episode, adding S. boulardii to antibiotics reduces recurrence from 65% to 35% (RR 0.43; 95% CI 0.20-0.97; P=0.04). 2
• The benefit is dose-dependent and antibiotic-specific: recurrence drops to 17% when combined with high-dose vancomycin (2 g/day) versus 50% with placebo, but shows no benefit with low-dose vancomycin (500 mg/day) or metronidazole. 3, 1
• For patients with initial CDI, S. boulardii provides no benefit (recurrence 19% vs 24% with placebo; P=0.86). 2

Primary Prevention

• Guidelines diverge on primary prevention. The AGA conditionally recommends S. boulardii for preventing CDI in adults and children receiving antibiotics (RR 0.41; 95% CI 0.22-0.79), representing a 59% reduction in C. difficile-associated diarrhea. 4, 1
• However, the 2018 IDSA/SHEA guidelines state that no probiotic, including S. boulardii, has demonstrated consistent, reproducible efficacy for primary prevention and make no recommendation for its use. 4, 1
• The WSES 2019 guidelines note limited direct evidence for adjunctive use in first episodes of CDI. 4

Dosing and Administration

Standard Regimen

• Dose: 1 g/day (approximately 3 × 10¹⁰ CFU) orally for 28 days. 1, 2, 3
• Initiate S. boulardii at the start of antibiotic therapy and continue throughout the entire antibiotic course. 1
• For recurrent CDI, combine with vancomycin 125 mg four times daily for 10-14 days, then continue S. boulardii for the full 28-day course. 2, 3

Antibiotic-Specific Requirements

• Effective only with high-dose vancomycin (≥2 g/day). 3, 1 The combination of high-dose vancomycin plus S. boulardii reduces recurrence to 16.7% compared to 50% with vancomycin alone (P=0.05). 3
• No benefit when combined with standard-dose vancomycin (500 mg/day) or metronidazole (1 g/day). 1, 3
• For multiply recurrent CDI (≥2 episodes), consider adding S. boulardii to tapered/pulsed vancomycin regimens, though evidence is weaker in this population. 1

Absolute Contraindications

• Immunocompromised patients (risk of fungemia from this yeast probiotic). 4, 1, 5
• Severely debilitated patients. 4, 1
• Patients at risk for bacteremia/fungemia or those with central venous catheters in critical illness. 1
• The AGA specifically warns that patients with severe illnesses should avoid probiotics due to potential harms. 4

Clinical Algorithm for Recurrent CDI

First Recurrence:

1. Confirm immunocompetent status before initiating probiotic. 4, 1
2. Start vancomycin 125 mg four times daily (or fidaxomicin 200 mg twice daily). 4, 1
3. Add S. boulardii 1 g/day only if vancomycin dose is escalated to ≥2 g/day. 1, 3
4. Continue S. boulardii for 28 days total, extending beyond antibiotic completion. 2, 3

Second or Subsequent Recurrence:

1. Use tapered/pulsed vancomycin as primary strategy (e.g., 125 mg four times daily for 10-14 days, then 125 mg twice daily for 7 days, then 125 mg daily for 7 days, then 125 mg every 2-3 days for 2-8 weeks). 4
2. Consider adding S. boulardii 1 g/day as adjunctive therapy, acknowledging limited evidence in multiply recurrent disease. 1
3. If multiple courses fail, evaluate for fecal microbiota transplantation. 4, 1

Evidence Quality and Guideline Strength

• The overall certainty of evidence for S. boulardii in CDI treatment is low to moderate due to heterogeneity in study populations and limited trial numbers. 4, 1
• The AGA makes no recommendation for probiotics in treating active CDI, citing insufficient evidence. 4
• The WSES provides a Grade 2B recommendation (weak recommendation, moderate evidence) for adjunctive S. boulardii in recurrent CDI based on two positive RCTs. 4, 1
• The IDSA/SHEA 2018 guidelines note that S. boulardii "has shown promise" but state that "none has demonstrated significant and reproducible efficacy in controlled clinical trials." 4

Common Pitfalls

• Do not use S. boulardii for initial CDI episodes—it provides no benefit and adds unnecessary cost. 2
• Do not combine with standard-dose antibiotics—efficacy requires high-dose vancomycin (≥2 g/day). 3, 1
• Do not use in immunocompromised patients—case reports exist of S. boulardii fungemia in vulnerable populations. 4, 1
• Metronidazole should not be used for recurrent CDI due to lower sustained response rates and neurotoxicity risk with prolonged use. 4
• The AGA identified potential publication bias with multiple registered trials never published, suggesting the true effect size may be smaller than reported. 4