Saccharomyces boulardii for the Prevention of Antibiotic-Associated Diarrhea in Hospitalized Patients Receiving Antibiotics: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic therapy, while evidence supporting Saccharomyces boulardii for its prevention among hospitalized adults in resource-constrained settings remains limited. We evaluated the efficacy of Bularen® in preventing AAD among hospitalized adults receiving systemic antibiotics. Methods: This single-center, randomized, double-blind, placebo-controlled trial was conducted at a tertiary care hospital in Bosnia and Herzegovina. Participants were randomly assigned to Bularen® (S. boulardii) 250 mg twice daily or a matching placebo for 28 days. The primary outcome was at least one episode of AAD, defined as two or more loose or liquid stools within 24 h, during the 28-day follow-up. Results: Of 435 patients screened, 100 were randomized to Bularen® (n = 51) or placebo (n = 49), and all completed follow-up. AAD occurred in 4/51 participants (7.8%) receiving Bularen® and 35/49 (71.4%) receiving placebo (risk ratio, 0.11; 95% confidence interval, 0.04-0.29; p < 0.001), corresponding to an absolute risk reduction of 63.6 percentage points. During intravenous antibiotic therapy, AAD occurred in 0% versus 26.5% of participants, respectively (p < 0.001), and during oral therapy in 7.8% versus 51.0% (risk ratio, 0.15; 95% confidence interval, 0.06-0.41; p < 0.001). No toxin-positive Clostridioides difficile infections were identified. Conclusions: Bularen® substantially reduced AAD incidence in this study population. Given the high placebo event rate and single-center design, confirmation in larger multicenter trials using standardized AAD definitions is warranted.