Nephrotoxicity in patients with vancomycin trough concentrations of 15-20 μg/ml in a pediatric intensive care unit

Abstract

Study objectives: To determine if a higher serum vancomycin (Vt) target trough concentration of 15-20 μg/ml or greater is associated with an increased rate of vancomycin-induced nephrotoxicity in children admitted to a pediatric intensive care unit (PICU), and to determine risk factors for developing vancomycin-induced nephrotoxicity.

Design: Retrospective cohort study.

Setting: A PICU within a freestanding tertiary care pediatric hospital.

Patients: A total of 113 patients received vancomycin for at least 48 hours The high-trough cohort (H group [57 patients]) received vancomycin therapy between November 2008 and June 2009 for pneumonia, bacteremia, or meningitis that was managed by a clinical pharmacist who directed dosage adjustments driven by a novel algorithm to attain a target Vt concentration of 15-20 μg/ml or greater; the control group (C group [56 patients]) received vancomycin therapy during the preceding 10 months (between January and October 2008) for pneumonia or meningitis using standard dosing guidelines with lower target Vt concentrations of 5-15 μg/ml.

Measurements and main results: The highest grade of renal dysfunction according to the Common Terminology Criteria for Adverse Events criteria, v.4.0, was recorded. The mean ± SD Vt was 17.8 ± 3.1 and 8.4 ± 3.1 in the H and C groups, respectively (p<0.001). The rate of grade 1 nephrotoxicity was not significantly different between groups (8.8% in the H group vs 5.4% in the C group; p=0.72). No patient in either group developed a higher grade of renal dysfunction. In the univariable analysis, duration of vancomycin therapy (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.01-1.02, p=0.003), use of extracorporeal membrane oxygenation (OR 1.32, 95% CI 1.13-1.75, p=0.003), and vasopressor use (OR 1.41, 95% CI 1.11-1.37, p<0.001) were associated with nephrotoxicity. In the multivariable analysis, vasopressor use (OR 11.1, 95% CI 1.4-85, p=0.021) and duration of therapy were associated with nephrotoxicity (OR 1.19, 95% CI 1.04-1.37, p=0.011).

Conclusion: Our observations suggest that maintaining Vt concentrations 15 µg/ml or greater is not associated with an increased rate of nephrotoxicity in a PICU population.