Nephrotoxicity in Patients with Vancomycin Trough Concentrations of 15–20 μg/ml in a Pediatric Intensive Care Unit

Study Objectives To determine if a higher serum vancomycin ( V t) 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 V t 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.