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Concomitant therapy with vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with acute kidney injury (AKI). Diabetic patients may be more susceptible to AKI due to various factors. In an observational, retrospective, cohort study of adults treated for diabetic foot infections (DFIs), rates of AKI were compared between groups receiving VAN+PTZ versus VAN+cefepime (CFP). Among 356 patients screened for inclusion, 210 were analyzed. Forty-nine of 140 patients (35%) in the VAN+PTZ group and 5 of 70 patients (7%) in the VAN+