Is AKI Incidence Higher With Levofloxacin or Piperacillin/Tazobactam?

Is AKI Incidence Higher With Levofloxacin or Piperacillin/Tazobactam?
Is AKI Incidence Higher With Levofloxacin or Piperacillin/Tazobactam?

NEW ORLEANS, LA—W. Cliff Rutter, PharmD, from the University of Kentucky HealthCare, Lexington, KY, presented at IDWeek 2016 that piperacillin/tazobactam was associated with higher rates of acute kidney injury (AKI) than levofloxacin. 

Compared to other beta-lactams, piperacillin/tazobactam tends to be associated with a higher incidence of AKI. Levofloxacin, a fluoroquinolone antibiotic, is used for similar indications as piperacillin/tazobactam and is typically considered non-nephrotoxic. Existing studies evaluating AKI in patients treated with piperacillin/tazobactam and vancomycin use alternative beta-lactam agents as the comparator group, which "may be flawed due to underlying nephrotoxic potential of these agents," described Dr. Rutter. Researchers conducted a retrospective cohort study to determine if there was a difference in the rate of AKI among patients treated with piperacillin/tazobactam and levofloxacin for ≥2 days.

Patients' demographic and clinical data were obtained from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust. The RIFLE criteria was utilized to assess AKI. 

Dr. Rutter explained, "Patients were matched on a baseline creatinine clearance, receipt of other nephrotoxic agents, and comorbidities that predispose to AKI." Moreover, patients receiving vancomycin in the levofloxacin arm were exactly matched to patients receiving vancomycin in the piperacillin/tazobactam arm. 

A total of 2,538 patients taking piperacillin/tazobactam and 1,134 patients taking levofloxacin were included in the analysis; 52% of patients were male with a median Charlson score of 4. AKI incidence was higher in the piperacillin/tazobactam group (24.6% vs. 12.6%; P<0.0001) where higher rates were correlated in each RIFLE criteria. 

The piperacillin/tazobactam group had higher AKI rates in the matched cohort (19.7% vs. 13.1%; P=0.0002). After adjusting for confounding variables, the piperacillin/tazobactam group had an adjusted odds ratio (OR) of 1.63 (1.26–2.10) compared to the levofloxacin group. After accounting for vancomycin exposure, the piperacillin/tazobactam and vancomycin patients had a higher likelihood of experiencing AKI than those receiving levofloxacin and vancomycin (30.6% vs. 16.9%; P=0.0004, aOR 2.17 [1.43–3.35]). 

On a similar note, patients receiving piperacillin/tazobactam alone were more likely to have an AKI compared to levofloxacin alone (15.6% vs. 11.7%; P=0.04, aOR 1.39 [1.02–1.92]) as evident in the matched cohort.

Findings from this comparator-controlled study showed that piperacillin/tazobactam was associated with higher AKI rates when compared to levofloxacin. "Additionally, the increase in AKI incidence when vancomycin was added to piperacillin/tazobactam was greater than when vancomycin was added to levofloxacin," Dr. Rutter added. 

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