Related Experiment Video

Updated: Jun 28, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

Kidney injury, dialysis, and mortality with vancomycin plus piperacillin-tazobactam or cefepime

Joseph Magagnoli1, Tammy H Cummings1, Christopher M Bland2

  • 1Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina; Center for Outcomes Research and Evaluation (CORE), College of Pharmacy, University of South Carolina, Columbia, SC, USA.

International Journal of Antimicrobial Agents
|June 26, 2026
PubMed
Abstract

Insights

Vancomycin-piperacillin/tazobactam combination is linked to higher creatinine-defined acute kidney injury (AKI), but not to increased dialysis or death risk. This suggests potential pseudo-nephrotoxicity rather than true kidney damage.

Area of Science:

  • Pharmacology
  • Nephrology
  • Clinical Pharmacy

Background:

  • Retrospective studies suggest vancomycin-piperacillin/tazobactam increases acute kidney injury (AKI) risk.
  • Recent prospective data indicate creatinine-based AKI may overestimate harm from this combination.
  • This study investigates severe renal outcomes beyond creatinine-defined AKI.

Purpose of the Study:

  • To evaluate the association between vancomycin-piperacillin/tazobactam and severe renal outcomes.
  • To compare vancomycin-piperacillin/tazobactam with vancomycin-cefepime regarding AKI progression, dialysis, and death.
  • To assess if creatinine elevations signify true kidney injury or pseudo-nephrotoxicity.

Main Methods:

  • Retrospective cohort study using the MIMIC-IV database.
  • Inclusion of adult hospitalizations receiving vancomycin with piperacillin-tazobactam or cefepime.
  • Multistate modeling with inverse probability of treatment weighting (IPTW) to analyze transitions to AKI, dialysis, and death.

Main Results:

  • Creatinine-defined AKI occurred more frequently with vancomycin-piperacillin/tazobactam (23.1%) versus vancomycin-cefepime (15.2%).
  • Piperacillin-tazobactam showed higher hazard for AKI (IPTW-adjusted HR 1.63) but not for progression to dialysis (HR 0.77).
  • In-hospital death risks were similar; death post-AKI was less frequent with piperacillin.

Conclusions:

  • Vancomycin-piperacillin/tazobactam is associated with increased creatinine-defined AKI.
  • This association did not translate to higher risks of dialysis or death.
  • Findings support pseudo-nephrotoxicity and highlight multistate modeling's value in drug safety assessment.
Keywords:
Acute kidney injuryCefepimeDrug safetyIn-hospital mortalityPiperacillin-58 tazobactamVancomycin

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