Piperacillin-Tazobactam Poses No Renal Risk in Adults With Sepsis

TOPLINE: A new study shows that piperacillin-tazobactam and cefepime are equally safe for acute kidney injury (AKI) in acute infection, with cefepime linked to more neurological issues.


  • The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the US Food and Drug Administration.

  • The ACORN trial included 2511 adults presenting to emergency department or intensive care unit (ICU) with suspected infection.

  • Within 12 hours of presentation, these individuals were prescribed either cefepime (n=1214) or piperacillin-tazobactam (n=1297).

  • The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.


  • The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio [OR], 0.95; P = .56).

  • The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95%CI, −1.0% to 3.8%).

  • Patients in the cefepime vs piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).


In an accompanying editorial, Dr Steven Y. C. Tong, Department of Infectious Diseases, University of Melbourne, Australia, and colleagues wrote, “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”


The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tennessee. It was published online on October 14, 2023 in the JAMA with an accompanying editorial.


  • The study was conducted at a single academic centre, which may limit the generalizability of findings.

  • Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.


The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared recieving travel grant, personal fees, honoraria, and unrelated research support from various sources.

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