Factors Affecting Vancomycin and Piperacillin–Tazobactam-Induced Nephrotoxicity

Background/Objectives: Nephrotoxicity caused by use of vancomycin and piperacillin–tazobactam has been heavily debated, and specific impact of this combination on development of acute kidney injury (AKI) has remained uncertain. We sought to further elucidate the risk factors contributing to nephrotoxicity. Methods: We conducted a retrospective cohort study at our academic medical center from May 2019 to March 2023. We included adult patients who received at least 48 h of dual vancomycin and piperacillin–tazobactam therapy. The primary outcome is incidence of kidney injury along with determinants of AKI. Patients were stratified into two groups according to occurrence of AKI or its absence. Demographic features, concomitant use of nephrotoxic agents, site of infection, use of vasopressors, duration of therapy, and vancomycin-level parameters were compared. Results: Of 350 patients, AKI occurred in 89 patients (25.4%). The 30-day mortality was comparable between the two groups. No significant differences were observed in age, gender, race, or comorbidities, although more AKI cases occurred in African American patients (51.7%). Elevated initial vancomycin trough and estimated area under the curve/minimum inhibitory concentration levels, higher mean body mass index (BMI), and use of intravenous (IV) contrast were more frequently observed in the AKI group. Conclusions: We demonstrated that 25.4% of patients receiving vancomycin and piperacillin–tazobactam combination experienced AKI, while higher BMI and use of concomitant IV contrast were significantly associated with increased nephrotoxicity. Therefore, we suggest proceeding with caution regarding use of vancomycin and piperacillin–tazobactam in patients with elevated BMI and those who have received IV contrast.