2250. Combination Vancomycin Plus Cefazolin for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Abstract

Abstract Background Combination β-lactam and vancomycin (VAN) prevent the emergence of resistance and result in synergistic antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. We sought to provide clinical translation to these data and determine if patients with MRSA bloodstream infection (BSI) treated with VAN + cefazolin (VAN/CFZ) via our MRSA BSI clinical pathway had improved clinical outcomes compared VAN alone. Methods Multicenter, retrospective, comparative cohort study from 2006 to 2019 in adults with MRSA BSI treated with VAN for ≥ 72 hours. VAN/CFZ was defined as VAN + CFZ within ≤ 72 hours of index culture for ≥ 24 hours. Other β-lactams were allowed for < 48 h in the VAN/CFZ group. The VAN alone group could not have other β-lactams within 7 days of treatment initiation. The primary outcome was clinical failure defined as a composite of 30-d all-cause mortality, 60-day recurrence, and persistent BSI (≥ 7 days). The independent effect of VAN/CFZ on clinical failure was evaluated with multivariable logistic regression. The primary safety endpoint was nephrotoxicity within 7 days of treatment initiation. Results A total of 237 patients were included (104 VAN/CFZ, 133 VAN). The most common BSI sources were skin/soft tissue (29.1%), IV catheter (21.9%), osteoarticular (20.3%) and infective endocarditis (16.0%). Demographic and clinical characteristics were similar between groups except VAN/CFZ had a higher median APACHE II score (18 vs. 13, P = 0.011). VAN/CFZ patients were also more likely to have received an infectious disease consult (100% vs. 81.2%, P < 0.001). Median (IQR) duration of CFZ was 115 (87–164) hours. After controlling for age, APACHE II score, ID consult and infection source, VAN/CFZ was associated with reduced odds of clinical failure (aOR 0.425, 95% CI 0.228, 0.792). Bivariate outcomes are shown in the table: Conclusion Patients with MRSA BSI treated with VAN/CFZ vs. VAN experienced fewer clinical failures, supporting additional studies evaluating the role of adjuvant CFZ for MRSA BSI. Disclosures All authors: No reported disclosures.