Acute Kidney Injury in Patients Treated with Beta-lactam/Beta-lactamase Inhibitor Combinations

Background: Recent literature has implicated the combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) in increasing incidence of acute kidney injury (AKI) compared to other combinations. The mechanism of this interaction is unknown, but may be due to the administration of a beta-lactamase inhibitor concomitantly. This study evaluated the difference in AKI rate among patients treated with ampicillin-sulbactam (SAM) compared to those receiving PTZ.

Methods: Clinical data from 9/1/2007 through 9/31/2015 were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust. Patients receiving SAM or PTZ for >48 hours were included. Patients were matched on: Charlson Comorbidity Index (CCI), baseline creatinine clearance, hypotension exposure, various nephrotoxic drug exposures, diagnosis of diabetes, heart failure, and hypertension. Basic descriptive statistics and multivariate regression were performed.

Results: Overall, 13,592 patient encounters were evaluated, with 612 and 12,980 receiving SAM and PTZ, respectively. On average, the PTZ group was slightly older (54 ± 17 vs 52 ± 15 years, p=0.0003), slightly less ill (CCI 3 [1-7] v 5 [2-9], p<0.00001), and had worse baseline creatinine clearance (91 [66-120] v 100 [78-128] mL/min, p<0.0001). AKI occurred in 2,934 (21.6%) patients in total, with 9.2% and 22.2% of SAM and PTZ patients experiencing AKI, respectively (p<0.00001). SAM patients were matched to 1836 PTZ patients. In the matched cohort 9.2% and 11.4% of SAM and PTZ patients experienced AKI, respectively (p=0.14). However, when VAN exposure is considered, the AKI rates are 8.9% SAM, 10.2% SAM+VAN, 9.5% PTZ, and 18.1% PTZ+VAN. After multivariate regression, receipt of PTZ+VAN was associated with an adjusted OR of 2.28 (95% CI 1.5-3.12, p <0.001) compared to PTZ alone. Whereas, receipt of SAM (p=0.56) or SAM+VAN (p=0.6) were not associated with increased odds of AKI.

Conclusion: AKI incidence was similar in patients treated with SAM and PTZ; however, the addition of VAN to PTZ significantly increased AKI incidence. This study demonstrates that the administration of multiple beta-lactam agents is not the likely mechanism for increased AKI observed with PTZ and VAN.