Abstract

Introduction: Clostridioides difficile infection (CDI) is the most common nosocomial infection associated with frequent recurrences. The optimal approach to reduce the risk of CDI remains unclear and patients frequently take probiotics such as Saccharomyces boulardii to prevent primary or recurrent CDI. We performed a systematic-review and meta-analysis to evaluate the role of S boulardii in preventing primary or recurrent CDI in patients on systemic antimicrobial therapy. Methods: A systematic search of MEDLINE, Embase and Web of Science was performed up to March 2021, followed by manual search of identified studies. We included case-control, cohort studies or clinical trials that included patients on systemic antimicrobial therapy who did or did not receive S boulardii and were evaluated for primary or recurrent CDI. Odds ratio estimates with 95% confidence intervals were calculated using a random effects model. Results: Six studies (two randomized controlled trials (RCTs), 1 prospective cohort, 3 retrospective cohort) including 11,127 CDI patients (all hospitalized) were evaluated for primary prevention. Follow up among the included studies ranged from 4-8 weeks after stopping antibiotics. Among these, the rate of recurrent CDI in patients who received S boulardii was 0.6% (46/6674) compared to 1.1% (53/4453) that did not receive S boulardii. Meta-analysis using random effects model showed no difference in risk of CDI among two groups (odds ratio [OR], 0.60; 95%CI, 0.31-1.15; P=0.34). There was no significant heterogeneity among the studies, with an I2 value of 11% (Figure A). Two RCTs (one with inpatients and one with both inpatients and outpatients), comprising a total of 92 patients evaluated S boulardii for recurrence prevention at 250 mg twice daily for 4 weeks in one study and for the duration of antibiotic use in the other study. The mean prior CDI episodes were 3.2 in 1 study and unavailable in the other. The rate of CDI in patients receiving S boulardii was 27.7% (12/44) compared to 60.4% (29/48) without S boulardii. Meta-analysis revealed a significant decrease in the risk of CDI in patients who received S boulardii (OR, 0.26; 95%CI, 0.11-0.63; P=0.003). There was no heterogeneity among the studies, with an I2 of 0%. (Figure B) Conclusion: Use of S boulardii appears to prevent recurrence in patients with a history of CDI who require systemic antimicrobial therapy. However, the use of S boulardii did not show any benefit for primary prevention of CDI in patients needing antibiotics.Figure 1.: Meta analysis showing efficacy of S boulardii for A) Primary prevention of CDI B) Prevention of Recurrent CDI.

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