Dr. Rhodes
Clinical question: Do piperacillin-tazobactam and cefepime have similar risks of acute kidney injury (AKI)?
Background: Observational studies have shown an association between piperacillin-tazobactam and AKI, especially when co-administered with vancomycin. Thus, cefepime has been widely thought to have a lower nephrotoxicity risk compared to piperacillin-tazobactam. However, no randomized controlled trials have been performed to compare the two drugs.
Study design: Randomized clinical trial
Setting: Single academic medical center in the Southeastern U.S.
Synopsis: This study randomized 2,511 patients who were ordered an antipseudomonal antibiotic in the emergency department (ED) or intensive care unit (ICU) to receive cefepime or piperacillin-tazobactam. The primary outcome was stage 3 AKI (using the Kidney Disease: Improving Global Outcomes [KDIGO] definition) or death by day 14, and there was no significant difference in this outcome between the two groups (OR, 0.95, 95% CI, 0.8 to 1.13). Coadministration rates of vancomycin were practically equivalent between both groups. The study also prespecified a secondary outcome of neurological dysfunction; patients receiving cefepime had fewer delirium- and coma-free days than the piperacillin-tazobactam group (OR, 0.79, 95% CI, 0.65 to 0.95). This study does have several significant limitations as it was only performed at a single institution. Also, neither patients nor clinicians were blinded to group assignment. However, this study does show that the widespread belief of the nephrotoxicity of piperacillin-tazobactam may not be true. It may, in some situations, be more favorable due to a lower risk of neurotoxicity compared with cefepime.
Bottom line: Piperacillin-tazobactam and cefepime have similar risks of AKI even when co-administered with vancomycin. Cefepime has a slightly higher risk of neurotoxicity.
Citation: Qian ET, Casey JD, et al. Cefepime vs piperacillin-tazobactam in adults hospitalized with acute infection: the ACORN randomized clinical trial. JAMA. 2023;330(16):1557-67.
Dr Rhodes is a med-peds hospitalist at Duke University Hospital and an assistant professor in the department of medicine at Duke University School of Medicine in Durham, N.C