The Effectiveness of a Vancomycin Dosing Guideline in the Neonatal Intensive Care Unit for Achieving Goal Therapeutic Trough Concentrations

Abstract

Concern for bacterial resistance and treatment failure with vancomycin trough concentrations < 10 μg/mL have led guidelines to increase goal concentrations. There is a paucity of data evaluating vancomycin dosage necessary to achieve goals in the neonatal intensive care unit (NICU). We aimed to evaluate the implementation of a new vancomycin dosing guideline in improving trough target attainment. This retrospective study evaluated neonates in the NICU treated with vancomycin between January 2009 and December 2015. Therapeutic trough concentration attainment (10-20 μg/mL) was compared between neonates receiving vancomycin per old versus new dosing guidelines. Vancomycin trough concentrations, modeled pharmacodynamic target attainment, and nephrotoxicity were compared between groups. A total of 212 vancomycin trough concentrations (n = 91 old and n = 121 new guideline) were evaluated in 182 unique neonates. The mean ± standard deviation trough concentration achieved was 18.0 ± 7.3 μg/mL vs 8.9 ± 4.8 μg/mL in the new and old guidelines, respectively (P < .01). The new guideline resulted in a higher percentage of neonates achieving trough concentrations of 10 to 20 μg/mL (62% vs 29%; P < .01) and decreased the percentage of neonates with subtherapeutic trough concentrations (9% vs 69%; P < .01). Pharmacokinetic modeling identified postmenstrual age, days of life, and urine output as predictors of vancomycin clearance and resultant trough and area under the curve values (P < .01 for all). Trough concentrations >10 μg/mL ensured area under the curve /minimum inhibitory concentration >400 in >90% of neonates when bacteria minimum inhibitory concentration was ≤ 1 μg/mL. Nephrotoxicity was similar between groups (8.3% vs 7.7%; P = .99). In conclusion, a vancomycin nomogram designed to achieve trough concentration of 10 to 20 μg/mL improves pharmacodynamic target attainment in neonates in the NICU.

Keywords: dosing guideline; neonatal; therapeutic drug monitoring; vancomycin.