Identification of vancomycin exposure target in neonates: how much is enough?

Abstract

Objectives: Vancomycin is commonly used in neonates with the same pharmacokinetics/pharmacodynamics (PK/PD) target as adults. However, no evidence supports this practice, and the association between trough concentrations and treatment outcomes has been widely questioned. This study aimed to identify the optimal PK/PD predictor and assess the correlation between AUC/MIC, trough concentration and the vancomycin efficacy in neonates.

Methods: This study retrospectively collected neonates who used vancomycin and constructed a population pharmacokinetic (PPK) model to estimate the AUC. Logistic analyses were used to identify the variables related to efficacy. Classification and regression tree analysis was used to explore thresholds. The correlation between trough concentration and AUC/MIC on the first day was analysed using a linear regression model.

Results: PPK modelling involved 131 neonates. Postmenstrual age and current weight were included in the covariate analysis. Forty-eight patients were included in the efficacy analysis, 13 of whom were infected with MRSA. The best-performance PK/PD target for efficacy was AUC0-24  h/MIC ≥ 331. The trough concentration was correlated with AUC0-24  h/MIC (r2 = 0.32), but individual differences existed. AUC0-24  h/MIC ranged up to 2.5-fold for a given trough concentration.

Conclusions: AUC0-24  h/MIC ≥ 331 was the optimal target of vancomycin efficacy in neonates. The trough concentration was not a reliable predictor of efficacy and AUC0-24  h/MIC. AUC-guided dosage adjustments are more valuable in clinical applications.