A National Retrospective Cohort Study Comparing the Effects of Cefepime Versus Piperacillin-Tazobactam on the Development of Severe Acute Kidney Injury in Patients With Septic Shock

Asad E Patanwala, David E Nix, Thomas E Hills, et al

Clin Infect Dis 2025; 80:770-776

https://doi.org/10.1093/cid/ciae600

Abstract

Background

Cefepime and piperacillin-tazobactam are commonly used broad-spectrum antibiotics used to treat patients with potential gram-negative bacterial sepsis. Piperacillin-tazobactam has been shown to be associated with acute kidney injury (AKI). However, it has not been compared with cefepime in patients with septic shock. We compared the effects of cefepime and piperacillin-tazobactam on the incidence of severe AKI in patients with septic shock.

Methods

This was a retrospective, multicenter, inverse probability-of-treatment weighted cohort study conducted in 220 geographically diverse community and teaching hospitals across the United States. Adult patients were included if they had septic shock on hospital admission and received cefepime or piperacillin-tazobactam. The proportions of patients in whom stage 3 AKI occurred during hospitalization were compared between groups.

Results

Of the 8427 patients included in the final cohort, 4569 received cefepime and 3858 received piperacillin-tazobactam. Patients had a mean (SD) age of 66.2 (15.2) years, and 45.3% were female; the mean (SD) estimated glomerular filtration rate was 48 (24) mL/min/1.73 m² on the day of admission. In the weighted cohort, stage 3 AKI occurred in 9.9% receiving cefepime and 9.8% receiving piperacillin-tazobactam (odds ratio, 0.98 [95% confidence interval, .84–1.15]; P = .82). In terms of secondary outcomes, there was no significant difference between cefepime and piperacillin-tazobactam with regard to renal replacement therapy, in-hospital death, major adverse kidney events, stage 1 AKI, stage 2 AKI, maximum recorded serum creatinine, or hospital length of stay