Incidence and Risk Factors for Vancomycin Nephrotoxicity in Acutely Ill Pediatric Patients

J Pharm Technol. 2018 Feb;34(1):9-16. doi: 10.1177/8755122517747088. Epub 2017 Dec 10.

Abstract

Background: Particularly with the current increased vancomycin dosing trends, the true risk of the agent's nephrotoxicity is not well characterized and remains of concern. Objective: To determine the incidence of vancomycin nephrotoxicity in acutely ill hospitalized children and to secondarily characterize the risk factors for this complication. Methods: A single-center retrospective cohort study conducted at UCSF Benioff Children's Hospital from June 2012 to June 2015. Inpatients 3 months to <19 years who received intravenous vancomycin for ≥48 hours were included. The primary outcome was incidence of nephrotoxicity, defined as an increase in serum creatinine by ≥50% from baseline. Univariate and multivariate analyses were conducted to identify risk factors for vancomycin nephrotoxicity. Results: A total of 291 patients (272 nonnephrotoxic and 19 nephrotoxic) were included in the analysis. Of the 19 patients, 12 (4.1%) were found to have moderate to severe toxicity. The median duration of therapy was 3 (3-5) and 4 (3-6) days for the group with "no nephrotoxicity" and "nephrotoxicity," respectively. The mean time for the serum creatinine to return to normal in patients with nephrotoxicity was 5.1 days. In the multivariate analysis, only final trough concentration ≥15mg/dL (odds ratio = 3.49, 95% confidence interval = 1.2-10.1; P = .021) and receipt of piperacillin/tazobactam (odds ratio = 3.14, 95% confidence interval = 1.02-9.6; P = .046) were significantly associated with nephrotoxicity. Conclusion: The rate of moderate to severe vancomycin-associated nephrotoxicity in acutely ill children is relatively uncommon and reversible. Kidney injury is associated with increased vancomycin trough concentrations and concomitant receipt of nephrotoxins, particularly piperacillin/tazobactam.

Keywords: antibiotics; nephrotoxicity; pediatrics; therapeutic drug monitoring; vancomycin.