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Association of Vancomycin Plus Piperacillin-Tazobactam With Acute Kidney Injury: Differentiating Pseudo-Injury From

Congqin Chen1, Rijing Zhou2, Jie Fang3

  • 1Department of Pharmacy, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Fujian Branch of National Clinical Research Center for Cardiovascular Diseases, Xiamen, China.

Clinical and Translational Science
|May 20, 2025
PubMed

Insights

The combination of vancomycin and piperacillin-tazobactam (VPT) may cause creatinine changes that mimic kidney injury, suggesting pseudotoxicity rather than true nephrotoxicity. Further research is needed to confirm the safety of VPT in severe infections.

Area of Science:

  • Pharmacovigilance
  • Nephrology
  • Infectious Diseases

Background:

  • Vancomycin and piperacillin-tazobactam (VPT) is a common combination for severe infections.
  • The potential for synergistic nephrotoxicity between VPT remains a clinical concern.
  • Distinguishing true kidney injury from artifactual changes is crucial for patient management.

Purpose of the Study:

  • To assess the risk of acute kidney injury (AKI) associated with VPT compared to other vancomycin regimens.
  • To investigate whether observed AKI signals with VPT represent true nephrotoxicity or pseudotoxicity.
  • To analyze safety signals using disproportionality analysis in a large adverse event database.

Main Methods:

  • Utilized the FDA Adverse Event Reporting System (FAERS) database via AERSMine.
  • Performed disproportionality analysis using Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN).
  • Compared VPT and vancomycin plus carbapenems (VC) regimens against other vancomycin-based treatments, analyzing overall AKI, creatinine changes, and severe AKI.

Main Results:

  • A safety signal for overall AKI and creatinine changes was detected with VPT in Model 1 (all reports).
  • No significant disproportionality signals were found for severe AKI, other biomarkers, or renal replacement therapy initiation with VPT.
  • No increased AKI risk signal was observed for vancomycin plus carbapenems (VC) compared to other vancomycin regimens.

Conclusions:

  • Creatinine-defined AKI associated with VPT may represent pseudotoxicity, not true nephrotoxicity.
  • The findings suggest that VPT's safety profile regarding kidney injury warrants further investigation.
  • Clarifying the distinction between true and pseudo-nephrotoxicity is essential for optimizing antibiotic use.
Keywords:
acute kidney injurycarbapenemspiperacillin‐tazobactampseudo‐injuryvancomycin

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