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Background The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading to propose cefepime as an alternative since 2017 in our reference center. The present study compared microbiological efficacy and tolerance of these two EAT strategies. Methods All adult patients with PJI empirically treated by vancomycin-cefepime (n = 89) were enrolled in a prospective observational study, and matched with vancomycin-piperacillin/tazobactam-treated historical controls (n = 89) according to a propensity score including age, baseline renal function and concomitant use of other nephrotoxics. The two groups were compared using Kaplan–Meier curve analysis and non-parametric tests (Fisher exact test and Mann–Whitney U-test) regarding: (i) the proportion efficacious empirical regimen (i.e., at least one of the two molecules active against the identified organism(s) based on in vitro susceptibility testing); and (ii) the incidence of empirical therapy-related adverse events (AE), classified according to the Common terminology criteria for AE (CTCAE). Results Among the 146 (82.0%) documented infections, the EAT was considered as efficacious in 77 (98.7%) and 65 (98.5%) of the piperacillin–tazobactam and cefepim-treated patients, respectively (P = 1.000). The rate of AE, and in particular AKI, was significantly higher in the vancomycin–piperacillin/tazobactam (n = 27 [30.3%] and 23 [25.8%%]) compared with the vancomycin-cefepim (n = 13 [14.6%] and 6 [6.7%]) group (P = 0.019 and <0.001, respectively; figure), leading to a premature EAT discontinuation in 20 (22.5%) and 5 (5.6%) patients (P = 0.002). Of note, no significant differences were observed between the two groups regarding sex (91 males; 51.1%), median age (68-year-old; IQR, 59.3–75), main comorbidities including baseline renal function and proportion of patients receiving other nephrotoxics, and vancomycin plasmatic overload. Conclusion The empirical use of vancomycin-cefepim in PJI was as efficient as vancomycin–piperacillin/tazobactam, and was associated with a significantly lower incidence of AKI. Disclosures All authors: No reported disclosures.

open forum infectious diseases

400. Comparison of Tolerance and Microbiological Efficacy of Cefepime and Piperacillin/Tazobactam in Combination with Vancomycin as Empirical Antimicrobial Therapy of Prosthetic Joint Infection: A Propensity-Matched Cohort Study