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

Abstract

The combination of vancomycin and piperacillin-tazobactam (VPT) is widely used for severe infections, but its potential synergistic nephrotoxicity remains debated. This study used the FDA Adverse Event Reporting System (FAERS) database via AERSMine to assess the risk of AKI with VPT and vancomycin plus carbapenems (VC), compared to other vancomycin-based regimens to evaluate the hypothesis of pseudo-nephrotoxicity versus true nephrotoxicity. Disproportionality analysis was performed using the reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). Model 1 included all vancomycin-associated reports, while Model 2 focused on reports from healthcare professionals. In Model 1, a safety signal was detected for overall AKI (ROR: 1.31, 95% CI: 1.26–1.37; IC025: 0.21) and changes in creatinine (ROR: 1.23, 95% CI: 1.10–1.38; IC025: 0.12) with VPT. In contrast, no significant disproportionality signal was observed for changes in other biomarkers (ROR: 0.89, 95% CI: 0.70–1.14; IC025: −0.38), severe AKI (ROR: 0.82, 95% CI: 0.76–0.89; IC025: −0.31), or renal replacement therapy (RRT) initiation (ROR: 1.08, 95% CI: 0.90–1.29; IC025: −0.09). No safety signal of increased risk of AKI was detected for VC versus other vancomycin-containing regimens across all subgroups. Model 2 confirmed this trend. These findings suggest that creatinine-defined AKI with VPT may represent pseudotoxicity rather than true nephrotoxicity. Further research is needed to clarify the safety profile of VPT.