Risk of acute kidney injury in patients on concomitant vancomycin and piperacillin-tazobactam compared to vancomycin and other beta-lactam agents: a large multicenter retrospective cohort study from China

ABSTRACT Acute kidney injury (AKI) associated with vancomycin (VAN) plus piperacillin-tazobactam (PTZ) remains controversial, with over two-thirds of current evidence originating from US populations. This study evaluated AKI risk with VAN/PTZ vs VAN plus other beta-lactams (BLs) in Chinese patients, where VAN plus meropenem dominates empirical therapy. This study included patients receiving >48 h of VAN combined with a single BL. We compared AKI risk between VAN/PTZ and VAN/other-BLs. The primary outcome was incidence of stages 2–3 AKI, and the secondary outcome was major adverse kidney events at 60 days (MAKE 60 ). Propensity score matching was used to match patients between comparison groups, and ORs were calculated. Among 8,460 screened patients, 5,632 were ultimately included: 279 received VAN/PTZ, 4,197 received VAN/carbapenems, and 1,156 received VAN/cephalosporins. Matched cohorts showed balanced demographics and clinical features. VAN/PTZ showed no elevated AKI risk when compared to VAN/other-BLs (OR = 1.20, 0.61–2.42), as well as compared to VAN/meropenem (OR = 1.13, 0.57–2.24) or VAN/cefepime (OR = 0.82, 0.34–1.96). Consistently, no elevated MAKE 60 was observed when VAN/PTZ compared to VAN/other-BLs (OR = 1.20, 0.61–2.42), VAN/meropenem (OR = 1.24, 0.76–2.01), or VAN/cefepime (OR = 0.65, 0.28–1.47). This large multicenter cohort of Chinese patients demonstrated that VAN/PTZ was not associated with increased risk of AKI or MAKE 60 . IMPORTANCE Acute kidney injury (AKI) associated with vancomycin (VAN) plus piperacillin-tazobactam (PTZ) remains controversial. Research evaluating this risk remains limited in Chinese cohorts. To the best of our knowledge, this multicenter retrospective cohort study is the largest study to date comparing the risk of AKI for VAN/PTZ against VAN plus other beta-lactams (BLs), VAN/meropenem (MEN), or VAN/cefepime (FEP) in the Chinese population. The study indicated that VAN/PTZ did not demonstrate an increased risk of stages 2–3 AKI and MAKE60 compared to VAN plus other BLs, as well as VAN/MEN, VAN/FEP. Our findings challenge common concerns about nephrotoxicity of VAN/PTZ mainly from Western populations and provide new safety evidence for clinical practice in China. While residual confounding inherent to observational designs remains a limitation, this study offers the highest-quality real-world evidence to date supporting non-inferior renal safety of VAN/PTZ relative to VAN plus other BLs in Asian populations.