Is there a Difference in Acute Kidney Injury Incidence Among Patients Treated with Piperacillin-tazobactam or Levofloxacin?

Background: Recent literature supports increased acute kidney injury (AKI) in patients treated with piperacillin-tazobactam (PTZ) and vancomycin; however, these studies utilize alternative ß-lactam as the comparator group, which may be flawed due to underlying nephrotoxic potential of these agents. This study sought to determine if there was a difference in AKI rate in patients treated with PTZ and levofloxacin (LEV).

Methods: This retrospective cohort study examined adult patients admitted between 1/1/2010 and 12/31/2014, who received at least 2 days of PTZ or LEV. Demographic and clinical data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust. AKI was assessed using the RIFLE criteria. Patients were matched on baseline creatinine clearance, receipt of other nephrotoxic agents, and comorbidities that predispose to AKI. Patients receiving vancomycin in the LEV arm were exactly matched to patients receiving vancomycin in the PTZ arm.

Results: Overall, 3672 patients were included for analysis (2538 PTZ and 1134 LEV). The average age was 52±17 years, 52% of patients were male, and median Charlson score was 4 (2-8). AKI incidence was higher in the PTZ group (24.6% v 12.6%, p<0.0001), with higher rates in each stratification of the RIFLE criteria. Baseline characteristics that were still different following matching were gender, race, Charlson comorbidity index, baseline creatinine clearance, hypertension, heart failure, and exposure to ACE inhibitors or contrast. The PTZ group had higher AKI rates in the matched cohort (19.7% vs 13.1%, p=0.0002). Controlling for confounding variables, the PTZ group had an adjusted OR of 1.63 (1.26-2.10) when compared to the LEV group. When taking into account vancomycin (VAN) exposure, PTZ+VAN patients were more likely to experience AKI than those receiving LEV+VAN (30.6 v 16.9%, p=0.0004, aOR 2.17 [1.43-3.35]). Similarly, patients receiving PTZ alone were more likely to have an AKI compared to LEV alone (15.6 v 11.7%, p=0.04, aOR 1.39 [1.02-1.92]).

Conclusion: In this comparator-controlled study, PTZ was associated with higher AKI rates than LEV. Additionally, the increase in AKI incidence when VAN was added to PTZ was greater than when VAN was added to LEV.