Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam

Clin Infect Dis. 2023 Feb 8;76(3):e1444-e1455. doi: 10.1093/cid/ciac670.


Background: 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).

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: ceftolozane-tazobactam; nephrotoxicity; piperacillin-tazobactam; vancomycin.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / epidemiology
  • Anti-Bacterial Agents / adverse effects
  • Drug Therapy, Combination
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Piperacillin / adverse effects
  • Piperacillin, Tazobactam Drug Combination / adverse effects
  • Retrospective Studies
  • Tazobactam / adverse effects
  • Vancomycin / adverse effects
  • beta-Lactams / adverse effects


  • Vancomycin
  • ceftolozane
  • Anti-Bacterial Agents
  • beta-Lactams
  • Piperacillin, Tazobactam Drug Combination
  • ceftolozane, tazobactam drug combination
  • Tazobactam
  • Piperacillin