Incidence of Nephrotoxicity Among Patients Initiated on Vancomycin and Β-lactam Combination Therapies

Abstract

Background Vancomycin and β-lactam combinations are used to provide empiric coverage in hospitalized patients. Recent literature has illustrated an increased incidence of nephrotoxicity with such combinations, predominantly with piperacillin-tazobactam and vancomycin. The objective of this study is to evaluate the incidence of nephrotoxicity among patients receiving vancomycin and piperacillin-tazobactam vs., cefepime, or aztreonam. Methods A retrospective, observational, cohort study was conducted at Hahnemann University Hospital in adult patients who received vancomycin plus piperacillin-tazobactam, cefepime, or aztreonam for at least 48 hours between June 2013 and August 2016. Patients were excluded if they had chronic kidney disease Stage III or higher or on continuous renal replacement therapy. The following data were collected: demographics, renal function, number of concomitant nephrotoxic agents, total duration of combination therapy, and vancomycin levels. The primary outcome was the incidence of nephrotoxicity according to the Risk Injury Failure End Stage Renal Disease (RIFLE) criteria. Secondary outcomes were the total length of hospital (LOS) and intensive care unit (ICU) LOS. Statistical analyses were conducted using the Analysis of Variance and the Chi-square test. Results A total of 757 charts were reviewed of which 203 were included in the analysis; 69 in the piperacillin-tazobactam arm, 74 in the cefepime arm, and 60 in the aztreonam arm. The incidence of nephrotoxicity as assessed by the RIFLE criteria was higher in the piperacillin-tazobactam arm (41%) compared with cefepime (15%) and aztreonam arms (17%); P = 0.052. Majority of patients with nephrotoxicity experienced injury according to the RIFLE criteria. No differences were found in the total LOS, ICU LOS, or duration of nephrotoxicity. Patients who experienced nephrotoxicity in the piperacillin-tazobactam arm occurred earlier upon antibiotic initiation at 48 hours compared with the other arms extending past 72 hours; P = 0.004. Conclusion There was a trend towards more patients experiencing nephrotoxicity in the piperacillin-tazobactam arm compared with the other groups. Clinicians should remain vigilant when utilizing combination therapy. Disclosures T. Bias, Merck: Grant Investigator, Research grant. The Medicines Company: Speaker’s Bureau, Speaker honorarium.