Evaluation of vancomycin individualized model-based dosing approach in neonates

Abstract

Background: Vancomycin is commonly used to treat methicillin-resistant staphylococcal infections in neonates. Consensus on its ideal dosing in neonates has not been achieved. Model-based dosing recently has evolved as an important tool to optimize vancomycin initial dosing. The aim of this is to evaluate a population pharmacokinetic model-based approach in achieving the vancomycin therapeutic target of an AUC_0-24 400 as recommended by the recent IDSA treatment guidelines. This model was implemented as a simple Excel calculator to individualize and optimize vancomycin initial dosing in neonates.

Methods: An Excel calculator was developed using a previously published population pharmacokinetic model in neonates. It was evaluated using retrospectively retrieved data. For each patient, the initial empiric dose was calculated using the proposed Excel model and the most widely used neonatal dosing references. The probability of achieving the target AUC_0-24 of >400 mg h/L using the model-based method was calculated and compared with that of the empiric doses using other references.

Results: This analysis included 225 neonates. The probability of achieving the target AUC_0-24 >400 was 89% using our model-based approach compared with 11%-59% using tertiary neonatal dosing references (p < 0.01 for all comparisons).

Conclusion: These innovative personalized dosing calculators are promising to improve vancomycin initial dosing in neonates and are easily applicable in routine practices.

Keywords: Neonates; Pharmacodynamics; Pharmacokinetics; Vancomycin.