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Background Methicillin-resistant Staphylococcus aureus (MRSA) is a serious nosocomial pathogen, and is listed as a “High Priority Pathogen” by the WHO due to concerns of antimicrobial resistance and lack of novel therapeutics. Even in vancomycin-susceptible MRSA, increased rates of treatment failure occur in the setting of an increased minimum inhibitory concentration (MIC) to vancomycin, which is considered the gold-standard of therapy. We performed a case series of 25 patients infected with MRSA with an elevated MIC to vancomycin. Additionally, we describe the use of combination therapy with beta-lactams for the management of these highly complex cases. Methods We conducted a retrospective case series of 25 patients hospitalized at MSH between 8/2014–5/2019 who were treated for MRSA bacteremia where the isolate had an MIC ≥ 2. Data was centralized into the REDCap program. Clonal typing of bacteria and analysis of clinical features were performed in SAS and R. Results In total, 25 patients developed MRSA bacteremia with a vancomycin MIC ≥ 2. The majority of cases involved infection from vascular access, arteriovenous fistula/graft, and septic joint/osteomyelitis. All 25 patients were initially treated with vancomycin, with modification of therapy varying widely depending on clinician. The most common vancomycin-alternative was daptomycin (14/25 patients, alone and in combination). Combination therapy with vancomycin or daptomycin and a beta-lactam was used in 9 cases (36% of cases). Average number of days to clearance was 18.3 (range 1–69 days). Univariate and multivariate analyses revealed significant correlation MRSA bacteremia with vancomycin MIC ≥ 2 and admission from a nursing home or skilled nursing facility (p=0.02), history of MRSA colonization (p=0.006), and persistent bacteremia (bacteremia &amp;gt;7 days)(p&amp;lt; .0.001). Conclusion With few novel therapeutics under development, management of MRSA bacteremia with a rising MIC to vancomycin is a clinical challenge for practitioners. In our case series we found that treatment is largely patient and practitioner-dependent, and far from standardized. Further definition of the clinical risk factors for development and novel therapeutic strategies will enable understanding of how to best manage these challenging infections. Disclosures All Authors: No reported disclosures

261. A Single-Center Case Series of Methicillin-Resistant S. aureus Bacteremia with Elevated Minimal Inhibitory Concentrations to Vancomycin