Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury

J Antimicrob Chemother. 2023 Feb 1;78(2):478-487. doi: 10.1093/jac/dkac416.


Background: Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown.

Objective: Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI.

Patients and methods: We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI.

Results: Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25).

Conclusions: We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Anti-Bacterial Agents / adverse effects
  • Child
  • Drug Therapy, Combination
  • Humans
  • Penicillanic Acid / adverse effects
  • Piperacillin* / adverse effects
  • Piperacillin, Tazobactam Drug Combination / adverse effects
  • Retrospective Studies
  • Tazobactam / adverse effects
  • Vancomycin
  • Young Adult


  • Piperacillin
  • Vancomycin
  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Tazobactam
  • Penicillanic Acid