Abstract Background Owing to the established path of bacterial entry and contamination-associated mechanisms, grade III open orthopedic fractures represent a substantial infection risk. Historically, the EAST Guidelines recommended covering Staphylococcus aureus and adding aminoglycoside gram negative coverage. Incorporating newer evidence, the Allegheny Health Network local guidelines rely on ceftriaxone to cover gram-negatives and add methicillin-resistant S. aureus coverage with vancomycin. Methods The electronic health records of adults admitted for a grade III open fracture between January 1, 2016, and October 31, 2021 were retrospectively reviewed. Patients who received cefazolin and gentamicin (CZ+GM) or ceftriaxone and vancomycin (CRO+VA) as their prophylaxis were included. We recorded rate of a composite treatment failure outcome of receipt of antibiotics for suspected infection, infection-related hospitalization, or subsequent debridement for injury site skin and soft tissue infection or osteomyelitis. Presence of acute kidney injury (AKI) within 7 days was also evaluated. Categorical variables were compared using the Chi-square or Fisher’s exact tests, and continuous variables by t-test or Wilcoxon Rank Sum. Results Patients in the CZ+GM group were younger, with a mean age of 42.6 years compared to 50.6 years in the CRO+VA group (p = 0.02). Otherwise, there were no significant differences between groups in demographics, mechanism and site of injury, timeline of care, or total number of surgical interventions. More patients in the CZ+GM arm met the composite primary treatment failure outcome, but it was not statistically significant (45% vs 32%, p = 0.2). There were similar rates of treatment failure at 30 days (21% vs 26%, p = 0.5) and for only osteomyelitis (8% vs 9%, p = 1). Patients receiving CZ+GM trended towards higher rates of AKI, but this was not statistically significant (26% vs 19%, p = 0.4). Conclusion The trend in numerically lower treatment failure rates in the CRO+VA group across all outcomes studied supports the current recommendations in the local institutional guidelines. Given our sample size, type II error may have occurred, and larger studies with greater power should analyze this question. Disclosures Derek N. Bremmer, PharmD, BCPS-AQ ID, Thermo Fisher Scientific: Honoraria.
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