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

Abstract

Study Objective Increased acute kidney injury (AKI) incidence has been reported in patients receiving piperacillin-tazobactam (PTZ) therapy compared to other beta-lactams. This study sought to determine if the addition of beta-lactamase inhibitors impact AKI incidence by comparing patients treated with PTZ or ampicillin-sulbactam (SAM). Design Retrospective cohort study Setting Large academic tertiary care hospital Patients Overall, 2,448 patients received PTZ (n=1,836) 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 (CrCl) < 30 mL/min. Patients were matched on Charlson Comorbidity Index (CCI), initial CrCl, 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 OR 0.87, 95% CI 0.59–1.25). The addition of vancomycin to PTZ increased the likelihood of AKI compared to PTZ alone (adjusted OR 1.77, 95% CI 1.26–2.46). Concomitant SAM and VAN therapy was not associated with a significant increase in AKI compared to SAM monotherapy (adjusted OR 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 beta-lactamase inhibitor is not likely the mechanism in the observed increased rates of AKI in patients treated with vancomycin and PTZ.

Nephrotoxicity of concomitant piperacillin/tazobactam and teicoplanin compared with monotherapy

“… 12–16 There are no studies comparing piperacillin and piperacillin/tazobactam with regard to nephrotoxicity. A matched-cohort study performed by Rutter and Burgess, 32 in which patients were stratified according to vancomycin exposure, compared piperacillin/tazobactam with ampicillin/sulbactam with regard to renal function. Results showed that the likelihood of AKI increased with the addition of vancomycin to piperacillin/tazobactam compared with piperacillin/tazobactam alone, but not when vancomycin was added to ampicillin/sulbactam.…”

“…The authors conclude that the addition of a β-lactamase inhibitor is not responsible for the increased rates of AKI observed in patients treated with piperacillin/tazobactam + vancomycin. 32 Another hypothesis suggests that the concomitant occurrence of interstitial nephritis (caused by piperacillin/tazobactam) and oxidative stress (caused by vancomycin) may lead to a stronger decline in renal function compared with monotherapy. However, a recent experimental study using a rat model showed no additional histopathological kidney injury with combination therapy when compared with monotherapy.…”

Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review

“…These studies suggest that baseline renal function or pre-existing renal disease is not associated with higher risk of AKI when treated with VPT as opposed to vancomycin alone. Renal impairment has not been shown to be predictive of VPT nephrotoxicity [14,15,[51][52][53][54] nor in other dual antimicrobial combinations with vancomycin [54]. In small studies, the limited numbers of patients with renal impairment precluded analysis for association with AKI [13].…”

Utilizing the Patient Care Process to Minimize the Risk of Vancomycin-Associated Nephrotoxicity

“…The mechanisms for the increased rates of nephrotoxicity with piperacillin-tazobactam have been unclear. Data suggest that the association is not due to the beta-lactamase inhibitor or the infusion strategy [32]. Some have even suggested that the increase in serum creatinine with piperacillin-tazobactam does not represent nephrotoxicity in these patients.…”