TDM of Gentamicin and Vancomycin, in Neonates, Using Dried Blood Spot Sampling.

Gentamicin and vancomycin, widely used in neonatology, are antibiotics with a narrow therapeutic index and a risk of nephrotoxicity and ototoxicity. For these drugs, therapeutic drug monitoring (TDM) is required, to optimize the efficacy and tolerance of these antibiotics.

In newborns, the TDM of these antibiotics is really available, because of physiological features, such as renal elimination and hepatic metabolism which are both very dependent on age and maturation. Thus, in newborn, there is a large interindividual variability of pharmacokinetic parameters, making the dosage adjustment of antibiotics very difficult.

Unfortunately, because of a limited blood mass, the TDM of these antibiotics is very rarely practiced in these children. The introduction of a Died blood spot (DBS), which uses only a single drop of blood (<50 μL) preserved in dried form, thus makes it possible to reduce the blood volume taken and avoid the venous intrusion. The dosage needs the use of liquid chromatography coupled with tandem mass spectrometry (LC-MSMS), the only sensitive technique to work with such a low blood volume.

We therefore wish to develop this approach coupling DBS and LC-MSMS, in neonatology, to evaluate the concentration of these nephrotoxic antibiotics (gentamicin and vancomycin), as TDM. The blood concentrations of the antibiotic, per 100 new-born term or premature (50 gentamicin, 50 vancomycin), are compared to the physiological state of the child (premature or not, intrauterine growth retardation or not), its hemodynamic status (shock or not) and its efficacy / toxicity, evaluated by the clinician using a questionnaire.

The use of this new sampling method, as an alternative to conventional blood sampling, makes it possible to better monitor the concentrations of gentamicin and vancomycin in neonatalogy, thus reducing the risk of toxicity of these antibiotics.