Comparative renal risk of long-term use of beta-lactams in combination with vancomycin across the continuum of care

BACKGROUND: Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin–tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT). METHODS: This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed. RESULTS: AKI occurred in 14.4% of patients in the VPT group (n = 15/104) compared to 5.5% in the other BL group (n = 40/722) (p < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7–12.0) days in the VPT group and 10.9 (5–22.7) days in the other BL group (p = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33–4.65), p = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group (n = 15/104) and 5.3% in the other BL group (n = 11/208) (p = 0.006). Receipt of VPT [HR: 2.55 (1.36–4.78), p = 0.004] and acyclovir [HR: 2.38 (1.19–4.74), p = 0.014) remained significantly associated with AKI in the multivariable model. CONCLUSION: Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy.