Vancomycin combined with piperacillin/tazobactam increases the risk of acute kidney injury compared with vancomycin plus other anti-pseudomonal beta-lactams: a systematic review and network meta-analysis

Objective: To explore whether vancomycin plus piperacillin/tazobactam actually increases nephrotoxicity compared with other anti-pseudomonal beta-lactams (BLs). Methods: PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang and VIP were searched from inception to October 2023. The primary outcomes were acute kidney injury (AKI) as defined as acute increase in serum creatinine of 0.3 mg/dL or 50% and severe Stage 2-3 AKI. Results: We included 70 studies (76 638 patients). Network meta-analysis indicated that vancomycin plus piperacillin/tazobactam was associated with significantly higher AKI risk than vancomycin plus cefepime (OR 2.55, 95% CI 2-3.28), vancomycin plus meropenem (OR 2.26, 95% CI 1.71-3.02) and vancomycin plus other uncommonly used BLs (OR 2.47, 95% CI 1.87-3.29). Also, vancomycin +piperacillin/tazobactam was associated with significantly higher Stage 2-3 AKI risk than vancomycin +cefepime (OR 2.22, 95% CI 1.34-3.62), vancomycin +meropenem (OR1.96, 95% CI 1.22-3.25) and vancomycin + uncommonly used BLs (OR 2.81, 95% CI 1.66- 4.91). Vancomycin plus piperacillin/tazobactam did not result in a significant difference in the incidence of receiving dialysis treatment, mortality, length of stay and time to AKI. Subgroup analyses of studies conducting propensity score matching demonstrated vancomycin +piperacillin/tazobactam was associated with significantly higher AKI rates than vancomycin +cefepime (OR 2.19, 95% CI 1.38-3.47) and vancomycin + meropenem (OR 1.38, 95% CI. 1.18-1.60). Subgroup analysis of critically ill patients and children indicated that vancomycin + piperacillin/tazobactam was associated with significantly higher AKI rates. Conclusions: Vancomycin +piperacillin/tazobactam significantly increased the risk of AKI and severe Stage 2-3 AKI compared with vancomycin plus other BLs. More prospective studies are needed.