title: Prospective validation of neonatal vancomycin dosing regimens is urgently needed.
abstract: BACKGROUND
  Although vancomycin is frequently used to treat neonatal late-onset sepsis, there is no consensus on the optimal dosing regimen. Because many neonates needed dosing adaptation due to suboptimal trough values, the vancomycin dosing regimen in our neonatal department was changed during 2012.
  
  
  OBJECTIVE
  We aimed to document the need for validation of neonatal vancomycin dosing by exploring serum trough levels achieved using 2 published dosing regimens (previous regimen: based on postmenstrual age and serum creatinine and new regimen: based on postmenstrual age and postnatal age) and to identify covariates associated with suboptimal vancomycin trough levels (<10 mg/L).
  
  
  METHODS
  Routine therapeutic drug monitoring serum trough levels quantified after initiation of intravenous vancomycin therapy and clinical covariates were retrospectively collected. Median vancomycin trough levels of both dosing regimens were compared using the Mann-Whitney U test. The influence of continuous and dichotomous covariates on achieving a suboptimal trough level was explored using the Van Elteren test (stratified Mann-Whitney U test) and Mantel-Haenszel test (stratified χ(2) test), respectively. Covariates significant in monovariate analysis were subsequently included in a logistic regression analysis.
  
  
  RESULTS
  In total, 294 observations (median current weight 1870 g [range = 420-4863 g] and median postmenstrual age 35.07 weeks [range = 25.14-56.00 weeks]) were included. Using the previous and new dosing regimens, 66.3% and 76.2% of trough levels, respectively, were below 10 mg/L. Overall, suboptimal vancomycin trough values were significantly associated with lower weight (birth weight and current weight) and age (gestational age and postmenstrual age).
  
  
  CONCLUSIONS
  The majority of vancomycin trough levels in neonates achieved using 2 published dosing regimens did not reach the target of 10 mg/L. This illustrates the urgent need for prospective validation of neonatal vancomycin dosing regimens. We anticipate that dosing regimens integrating covariates reflecting general physiological maturation and renal maturation, as well as disease characteristics, could improve vancomycin exposure in neonates.
authors: Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium ; Department of Development and Regeneration, K U Leuven, Leuven, Belgium.
authors: Anaïs
authors: A
authors: Vandendriessche
authors: Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium ; Department of Development and Regeneration, K U Leuven, Leuven, Belgium.
authors: Karel
authors: K
authors: Allegaert
authors: Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium ; Department of Development and Regeneration, K U Leuven, Leuven, Belgium.
authors: Veerle
authors: V
authors: Cossey
authors: Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium ; Department of Development and Regeneration, K U Leuven, Leuven, Belgium.
authors: Gunnar
authors: G
authors: Naulaers
authors: Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium ; Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors: Veroniek
authors: V
authors: Saegeman
authors: Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium ; Department of Development and Regeneration, K U Leuven, Leuven, Belgium.
authors: Anne
authors: A
authors: Smits
keywords: dosing regimen; neonate; therapeutic drug monitoring; vancomycin