Dayu Chen,1– 3,* Jingjing Kan,2,* Qiaoling Gu,2,* Yi-Chen Li,1– 3 Yunxing Liu,1– 3 Mengzhu Kong,1– 3 Jinchun Liu,1– 3 Haixia Zhang1– 3 

1Department of Pharmacy, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China; 2Department of Pharmacy, Nanjing Drum Tower Hospital, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 3Nanjing Medical Center for Clinical Pharmacy, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jinchun Liu; Haixia Zhang, Email liujinchun@njglyy.com; zhx_510@hotmail.com

Abstract: In recent years, the increased use of vancomycin (VAN) in combination with piperacillin-tazobactam (TZP) has raised significant concerns in clinical practice regarding the heightened risk of acute kidney injury (AKI). This topic has become a focal point in clinical therapeutics due to the widespread application of VAN alongside TZP. The specific mechanisms underlying vancomycin and piperacillin-tazobactam (VPT) associated AKI remain unclear. In this review, we discuss several controversial or underexplored aspects of current research. While the majority of literature links VPT to an elevated risk of AKI, numerous studies present conflicting outcomes. Mechanisms proposed for the increased risk of AKI associated with VPT, based on clinical observations and animal studies, include additive toxic effects, increased VAN exposure due to concomitant use with TZP, exacerbated VAN-induced oxidative stress injury in proximal renal tubule by TZP, pseudo-nephrotoxicity mediated by VPT-induced impaired creatinine secretion, or a combination of the aforementioned mechanisms. Additionally, this review outlines potential strategies that might effectively mitigate the risk of VPT-induced AKI, offering insights and future implications in the realm of pharmacovigilance.

Keywords: vancomycin, piperacillin-tazobactam, acute kidney injury, nephrotoxicity, concomitant therapy