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Background Empiric antibiotic therapy for sepsis of unknown origin is typically broad spectrum and covers P. aeruginosa and methicillin-resistant S. aureus (MRSA). Nephrotoxicity is a well-known adverse event of IV vancomycin and literature suggests that combination with piperacillin/tazobactam may increase risk for acute kidney injury (AKI) as compared to combination with other beta-lactams. However, evidence is conflicting. The primary outcome of this study was to compare incidence of AKI in septic patients treated with IV vancomycin and piperacillin/tazobactam (VZ) vs. cefepime (VC). Secondary outcomes include hospital length of stay, inpatient mortality, and impact to direct variable cost. Methods Adult patients discharged with a sepsis diagnosis code who received VZ or VC for ≥24 hours in 2012–2019 were retrospectively identified. AKI was defined using RIFLE criteria. Patients were excluded for ESRD on HD, AKI occurring &amp;lt; 48 hours after treatment initiation or &amp;gt;7 days after discontinuation, pregnancy, febrile neutropenia, or meningitis. Statistical analysis controlled for many factors including age, race, gender, Elixhauser comorbidity burden, hours to first antibiotic dose, length of stay, and receipt of concomitant nephrotoxins. Results A total of 12,405 patients were evaluated; 7,818 received VZ and 3,096 received VC. Patients given VC had a 40% reduction in risk of AKI compared to those given VZ (IRR 0.600; 95% CI 0.46–0.78). These patients also had a 4% reduction in risk of having one additional inpatient day (IRR 0.961; 95% CI 0.937–0.985). Patients who received VZ and experienced AKI were 82.3% more likely to die inpatient compared to patients that did not (IRR 1.822; 95% CI 1.50–2.21). Patients treated with VC incurred less in average direct variable cost than those treated with VZ (p = 0.034) and those who suffered AKI also incurred more on average than those without AKI (p = 0.005). Conclusion Compared to septic patients treated with VZ, those treated with VC had significantly decreased risk of AKI as defined by RIFLE criteria. Patients who received VZ were at higher risk for a longer hospital stay and, if they also experienced AKI, inpatient mortality. VZ was associated with higher direct variable cost and patients with AKI incurred more dollars per encounter than those without AKI. Disclosures All Authors: No reported disclosures

50. Comparative Incidence of Acute Kidney Injury in Septic Patients Treated with Vancomycin in Combination with Piperacillin/Tazobactam vs. Cefepime