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Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T. © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail:


Sara Alosaimy, Abdalhamid M Lagnf, Athena L V Hobbs, Musa Mubarez, Wesley D Kufel, Taylor Morrisette, Radhika S Polisetty, David Li, Michael P Veve, Sam P Simon, James Truong, Natalie Finch, Veena Venugopalan, Matthew Rico, Lee Amaya, Christine Yost, Ashley Cubillos, Elisabeth Chandler, Megan Patch, Ian Murphy Kelsey Smith, Mark Biagi, Justin Wrin, W Justin Moore, Kyle C Molina, Nicholas Rebold, Dana Holger, Ashlan J Kunz Coyne, Sarah C J Jorgensen, Paige Witucki, Nikki N Tran, Susan L Davis, George Sakoulas, Michael J Rybak. Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023 Feb 08;76(3):e1444-e1455

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PMID: 35982631

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