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Pharmacotherapy. 2014 Jul;34(7):670-6. doi: 10.1002/phar.1442. Epub 2014 May 22.

Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam.

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  • 1Department of Pharmacy, Duke University Hospital, Durham, North Carolina.



To determine whether the addition of piperacillin-tazobactam leads to an increased incidence of nephrotoxicity in patients receiving vancomycin and to explore potential confounding factors that may increase the risk of vancomycin-induced nephrotoxicity.


Single-center, retrospective cohort study.


Large, academic, tertiary-care hospital.


One hundred ninety-one adults hospitalized between July 1, 2009, and July 1, 2012, with normal baseline renal function who received a minimum of 48 hours of vancomycin for any indication were included in the analysis. Of these patients, 92 received a minimum of 48 hours of intravenous piperacillin-tazobactam concurrently with vancomycin, with piperacillin-tazobactam being initiated within 48 hours of the initiation of vancomycin (combination group); 99 received vancomycin without piperacillin-tazobactam (vancomycin group).


A univariate analysis was performed to assess the effect of the following risk factors on the incidence of nephrotoxicity within the first 7 days of vancomycin treatment: concomitant nephrotoxic agents, advanced age, steady-state vancomycin trough concentration of 15 μg/ml or greater, elevated Charlson Comorbidity Index, and a total daily vancomycin dose of 4 g or greater. A multivariate model was constructed to compare the incidence of the primary end point of nephrotoxicity, defined as a minimum 1.5-fold increase in serum creatinine concentration, between groups. Nephrotoxicity developed in 8 (8.1%) of 99 patients in the vancomycin group and in 15 (16.3%) of 92 patients in the combination group (1-sided χ(2) test, p=0.041). In the univariate analysis, only vancomycin trough concentration of 15 μg/ml or greater (odds ratio 3.67) was associated with an increased risk of developing nephrotoxicity. In the multivariate analysis, patients with piperacillin-tazobactam added to vancomycin exhibited an increased incidence of nephrotoxicity, with an odds ratio of 2.48 (1-sided χ(2) test, p=0.032).


We observed an increased incidence of nephrotoxicity in vancomycin-treated patients who received concomitant piperacillin-tazobactam. A steady-state vancomycin trough concentration of 15 μg/ml or greater was also associated with an increased risk of the development of nephrotoxicity. These findings should be confirmed in larger, randomized studies.

© 2014 Pharmacotherapy Publications, Inc.


acute kidney injury; nephrotoxicity; piperacillin-tazobactam; vancomycin

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