Evaluation of a new Dutch vancomycin dosage guideline in preterm and term neonates.

A recent retrospective study performed within the AMC demonstrated that the
previously used vancomycin doses for term and preterm neonates possibly
produces subtherapeutic serum concentrations in the majority of these patients.
Conclusions were based on retrospective chart data from a limited number of
cases. Based on this report and other (sparse) evidence of suboptimal
vancomycin dosing, a new pediatric Vancomycin dosing schedule was introduced on
the Dutch Kinderformularium website in May 2015. The Academic Medical Center,
Emma Children*s Hospital has adopted this national dosing guideline.
However, as even the rationale for this national dosing guideline is under
debate and well-designed prospective PKPD studies are lacking. We will
prospectively investigate the first therapeutic vancomycin trough
concentrations in a cohort of consecutive neonatal cases receiving the adapted
doses.

The main objective of this study is to determine the number of therapeutic
first trough levels (vancomycin serum concentrations between 10 and 15 mg/L),
as well as subtherapeutic (serum concentrations < 10 mg/L) and supratherapeutic
(serum concentrations > 15 mg/L) first trough levels, when receiving the new
dosing regimens. Five categories of cases will be studied:
I: premature < 1 week,
II: premature 1 - 4 weeks,
III: term neonate < 1 week,
IV: term neonate 1 - 4 weeks,
V: infants > 1 month.
The secondary objective of this study is the determination of inter-patient
variability in pharmacokinetic parameters and drug exposure, expressed as area
under the curve/minimum inhibitory concentration (AUC/MIC).

This is a prospective and observational study with use of clinically scheduled
blood level measurements and possible additional measurements in blood samples
obtained from left over material.

The first trough serum vancomycin concentration will be determined 30 minutes
prior to the 5th dose according to clinical TDM routine.
Clinically scheduled blood samples will be obtained from either indwelling
arterial catheters or from venous blood sampling procedures. This is routine
practice at the NICU. Leftover material from other samples will be used for the
additional 3 samples and will be sent to the pharmacy laboratory for possible
additional plasma level investigations. In total, 4 blood samples are needed to
attain a correct population pharmacokinetic profile. Of these 4, 1 sample is
obtained by clinical routine and the other 3 by investigating leftover material
from other clinically indicated blood samples. The risk for the subjects is
negligent. There will be no interventions performed outside the normal clinical
routine.
This study will generate information regarding the adequacy of the existing and
new dose regimens of vancomycin in term and preterm neonates, as well as
pharmacokinetic parameters for this specific group of newborn patients. The
availability of these population pharmacokinetic parameters is of clinical
benefit, as it will further improve the vancomycin dosing regimens for this
fragile population.