Modelling of saliva gentamicin concentrations in neonates receiving gentamicin treatment

In neonatology wards, neonates are often admitted due to suspected infection.
In the Netherlands, neonatologists often prescribe the aminoglycoside
antibiotic gentamicin. Gentamicin has a small therapeutic index and therefore,
therapeutic drug monitoring has to be performed. This is done by taking two
blood samples (peak and trough levels), which causes a considerable burden for
the neonate. Therefore, a non-invasive method of therapeutic drug monitoring,
for example in saliva, would be preferred.
An earlier study has demonstrated a good correlation between saliva and plasma
gentamicin concentrations in children receiving a once-daily gentamicin
infusion.
This study aims to determine a correlation between saliva and serum gentamicine
concentrations in different neonatal subgroups. We will use population PK
modelling techniques to fit a model and use this model to calculate serum
gentamicin concentrations.

Primary objective:
To establish whether saliva samples could be used as an alternative for blood
samples in the therapeutic drug monitoring for gentamicin. To meet this
objective, a PK model will be developed for gentamicin saliva concentrations.

Secondary objective:
To describe the relation between the saliva PK model and the plasma PK model.
To reduce the number of invasive blood samples in this fragile poulation.

Observational non-interventional study using gentamicin concentration
measurements from saliva samples and clinically planned plasma gentamicin
measurements. Additional measurements of gentamicin levels in plasma will be
taken from leftover material.

The peak- and through serum gentamicin concentrations are determined according
to clinical routine. These samples are obtained from either indwelling
catheters or from venous blood sampling procedures. No additional blood samples
are scheduled for this study.
The saliva samples are drawn using the SalivaBio Infant's Swab. These swabs are
designed specifically for the collection of saliva of young infants and can be
held during sampling, eliminating the risk of asphyxiation. The time-points of
saliva sampling are paired with clinical routine (i.e. before feeding), so that
the infants are not disturbed more frequently when participating in this study.
This study will provide information concerning the possibility to perform
therapeutic drug monitoring of gentamicin in neonates using saliva gentamicin
concentrations. If this is found to be a valid alternative, it will be no
longer required to draw blood from neonates for therapeutic drug monitoring of
gentamicin in the future.
This study concerns a specific population with specific characteristics.
Therefore, it is not possible to conduct this study in adult patients or test
animals.