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Background Conflicting evidence in smaller randomized trials and meta-analyses regarding the protective effects of probiotics against Clostridium difficile infection underscore the need for further study. Our objective was to evaluate the effect of a single probiotic strain, Saccharomyces boulardii, at a standardized dose on hospital-onset C. difficile (HO-CDI) rates within hospitalizations administered broad-spectrum antibiotics. Methods Retrospective cohort study merging hospital prescribing data with C. difficile case data from the National Health Safety Network at a 220-bed level-2 trauma center nonacademic hospital. A convenience sample of 8,763 hospital admissions administrated at least one dose of a fluoroquinolone, clindamycin, or β-lactam class antibiotic during hospitalization was assessed. Hospitalizations were categorized by whether antibiotics were administered alone (control) or in conjunction with S. boulardii 20 billion colony-forming units daily (intervention). Associations between S. boulardii administration and HO-CDI incidence was evaluated by multivariate logistic regression. A sub-group analysis evaluated the extent to which administering S. boulardii within or after 24-hours of antibiotic start changed the effect. Propensity scores incorporated to account for selection bias. Results Hospitalizations where S. boulardii was co-administered with antibiotics had a reduced likelihood of HO-CDI (OR = 0.56, 95% CI 0.32 – 0.93) compared with control hospitalizations. S. boulardii administered within 24-hours of antibiotic start had a reduced likelihood of HO-CDI (OR = 0.40, 95% CI 0.21 – 0.75). No effect observed if S. boulardii administered after 24-hours (OR = 0.86, 95% CI 0.45 – 1.64). Post-hoc analysis for disease latency, the average number of days to HO-CDI onset was 5.6, 6.4, and 8.0 days for antibiotic only, S. boulardii after 24-hours, and S. boulardii within 24-hours of antibiotic, respectively (P &lt; 0.04). Conclusion Co-administering S. boulardii with broad-spectrum antibiotics is associated with a reduced risk of C. difficile in hospitalized patients, especially if started within 24-hours of antibiotic initiation. S. boulardii should be considered as preventative intervention to reduce the risk of HO-CDI. Disclosures All authors: No reported disclosures.

open forum infectious diseases

2420. Reduced hospital-onset Clostridium difficile infection incidence following Saccharomyces boulardii co-administration with broad-spectrum antibiotics during hospitalization.