Acute kidney injury risk associated with piperacillin/tazobactam compared with cefepime during vancomycin therapy in hospitalised patients: a cohort study stratified by baseline kidney function

- Risk of AKI with vancomycin + piperacillin/tazobactam (VPT) versus vancomycin + cefepime (VC) was compared.
- Elevated risk of AKI in hospitalised patients receiving VPT was compared with VC.
- Association was true in patients with normal renal function but not in those with pre-existing renal impairment.
- Future studies evaluating drug-associated AKI should consider stratification by baseline renal function.

Recent studies have found an association between piperacillin/tazobactam when added to vancomycin and acute kidney injury (AKI) risk. However, studies were limited by the small sample size and residual confounding. The aim of this study was to compare the risk of AKI with vancomycin plus piperacillin/tazobactam (VPT) versus vancomycin plus cefepime (VC) and to examine whether pre-existing renal impairment mediates the risk. This was a retrospective cohort study using electronic health records for patients admitted to two hospitals in 2012-2013. The outcome, AKI, was defined as an increase in serum creatinine level of ≥0.3 mg/dL or ≥50% from baseline. Patients were stratified by level of renal impairment as estimated by baseline creatinine clearance. Inverse probability of treatment weighting was used to balance baseline covariates between groups. Cox proportional hazards regression was used to evaluate VPT risk of AKI compared with VC. A total of 935 (17.53%) AKI cases were identified among 5335 patients receiving VPT or VC. VPT was associated with a higher risk of AKI relative to VC, with an adjusted hazard ratio (aHR) of 1.25 [95% confidence interval (CI) 1.11-1.42] in the total population and 1.70 (95% CI 1.44-2.02) in patients with normal baseline renal function. However, no elevated risk was found in patients with prior renal impairment (aHR = 0.81, 95% CI 0.65-1.01). VPT was associated with a higher risk of AKI relative to VC. The association was true in patients with normal renal function but not in those with pre-existing renal impairment.