Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy

Veena Venugopalan; Nicole Maranchick; Devorah Hanai; Yaima Jimenez Hernandez; Yuliya Joseph; Amanda Gore; Kathryn Desear; Charles Peloquin; Michael Neely; Timothy Felton; Bethany Shoulders; Mohammad Alshaer

doi:10.1093/jacamr/dlad157

Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy

JAC Antimicrob Resist. 2024 Jan 22;6(1):dlad157. doi: 10.1093/jacamr/dlad157. eCollection 2024 Feb.

Authors

Affiliations

¹ Department of Pharmacy, UF Health Shands Hospital, Gainesville, FL, USA.
² Department of Pharmacy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA.
³ Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Division of Immunology, Immunity to Infection and Respiratory Medicine, The University of Manchester, Manchester, UK.

Abstract

Objectives: Acute kidney injury (AKI) is a well-documented adverse effect observed with piperacillin/tazobactam in combination with vancomycin. The pharmacokinetics of these antibiotics when given in combination have not been previously evaluated. The purpose of this study was to compare the exposure of vancomycin + piperacillin/tazobactam in patients with and without AKI.

Methods: Ninety adult patients, who received at least 72 h of vancomycin + piperacillin/tazobactam combination therapy and had available serum concentrations of vancomycin and piperacillin were included in the study. Nephrotoxicity was defined as a 1.5-fold increase in serum creatinine within 7 days from baseline. Median daily AUCs were calculated in those with nephrotoxicity (vancomycin + piperacillin/tazobactam 'N') versus those without nephrotoxicity (vancomycin + piperacillin/tazobactam 'WN') during the first 7 days of combination therapy.

Results: The overall incidence of AKI in those receiving vancomycin + piperacillin/tazobactam was 20% (18/90). The median daily vancomycin AUCs did not differ between the vancomycin + piperacillin/tazobactam 'WN' and vancomycin + piperacillin/tazobactam 'N' groups. Although not statistically significant, the median daily vancomycin AUCs in the vancomycin + piperacillin/tazobactam 'N' group were numerically greater on Day 5 and trended downwards thereafter. For the piperacillin group, the median daily AUCs did not vary between groups, except on Day 7 where the vancomycin + piperacillin/tazobactam 'WN' group had statistically greater median piperacillin AUC than the vancomycin + piperacillin/tazobactam 'N' group (P = 0.046).

Conclusions: Utilizing serum creatinine-defined AKI, our study did not find any significant differences in vancomycin and piperacillin/tazobactam exposure between the groups with and without nephrotoxicity. These data indicate that vancomycin + piperacillin/tazobactam should not be avoided due to the risk of overexposure; instead, clinicians should continue to use these therapies cautiously.