The Relationship of Nephrotoxicity to Vancomycin Trough Serum Concentrations in a Veteran's Population: a Retrospective Analysis

Background: The risk of vancomycin-associated nephrotoxicity varies greatly depending on the trough concentration. Recent guidelines suggest target vancomycin trough concentrations of 15-20 mg/L as a predictor of efficacy in the treatment of severe gram-positive infections. Limited data exist quantifying the risk for nephrotoxicity with various ranges of vancomycin troughs.

Objective: To determine the occurrence of nephrotoxicity during vancomycin therapy and up to 72 hours after its completion, in relation to the maximum trough concentration value, and identify risk factors that impact nephrotoxicity associated with vancomycin use.

Methods: We reviewed the medical records of veterans with a baseline serum creatinine less than 2 mg/dL who received 48 or more hours of vancomycin therapy and had 1 or more vancomycin trough samples obtained within 96 hours of therapy initiation from January 1, 2006, to November 1, 2008, to determine the occurrence of nephrotoxicity (as defined by RIFLE [Risk, Injury, Failure, Loss, and End-stage renal disease] criteria).

Results: Thirty-four (12.6%) patients developed nephrotoxicity. In multiple logistic regression analysis, maximum trough concentrations (OR 1.14; 95% CI 1.09 to 1.20), documented hypotension (OR 4.7; 95% CI 1.3 to 16.4), and weight (OR 1.02; 95% CI 1.0 to 1.03) were found to be significantly associated with the occurrence of nephrotoxicity. Once stratified into ranges of 5-10 mg/L (4.9%), 10.1-15 mg/L (3.1%), 15.1-20 mg/L (10.6%), 20.1-35 mg/L (23.6%), and greater than 35 mg/L (81.8%), increasing trough ranges were associated with a subsequently higher risk of nephrotoxicity.

Conclusions: In the population evaluated, hypotension and trough concentrations were predictors of nephrotoxicity; elevated vancomycin trough concentration had the highest odds of association. These data reinforce the close therapeutic monitoring guidelines for vancomycin trough concentrations, especially when targeting troughs of 15-20 mg/L.