Acute Kidney Injury in Patients Treated with IV Beta-Lactam/Beta-Lactamase Inhibitor Combinations

Study Objective: Increased acute kidney injury (AKI) incidence has been reported in patients receiving piperacillin-tazobactam (PTZ) therapy compared with other β-lactams. The authors sought to determine if the addition of β-lactamase inhibitors impacts AKI incidence by comparing patients treated with PTZ or ampicillin-sulbactam (SAM). Design: Retrospective cohort study. Setting: Large academic tertiary care hospital. Patients: Overall, 2448 patients received PTZ (n=1836) or SAM (n=612) for at least 48 hours between September 1, 2007, and September 30, 2015. Patients were excluded for pregnancy, cystic fibrosis, chronic kidney disease, and initial creatinine clearance < 30 ml/min. Patients were matched on Charlson Comorbidity Index, initial creatinine clearance, hypotension exposure, various nephrotoxic drug exposures, history of diabetes, heart failure, and hypertension. Measurements and Main results: AKI occurred in 265 patients at similar rates for both groups (PTZ 11.4% vs SAM 9.2%; p=0.14). After stratifying by vancomycin exposure and controlling for confounders, there was no difference in the risk of AKI for SAM or PTZ (adjusted odds ratio [aOR] 0.87, 95% confidence interval [CI] 0.59–1.25). The addition of vancomycin (VAN) to PTZ increased the likelihood of AKI compared with PTZ alone (aOR 1.77, 95% CI 1.26–2.46). Concomitant SAM and VAN therapy was not associated with a significant increase in AKI compared with SAM monotherapy (aOR 1.01, 95% CI 0.48–1.97). Conclusion: Rates of AKI were similar for PTZ and SAM in a matched cohort. The addition of a β-lactamase inhibitor is not likely the mechanism in the observed increased rates of AKI in patients treated with vancomycin and PTZ.