Kinetically guided therapy with gentamicin in critically ill septic preterm newborns in the first week of life. An open – label prospective study (part I)

Authors: P. Pokorná 1;  J. Záhora 3;  J. Chládek 2;  V. Vobruba 1;  I. Selke-Krulichová 3;  Š. Studená 2;  J. Chládková 4;  J. Martinková 2
Authors‘ workplace: Jednotka intenzivní a resuscitační péče, Klinika dětského a dorostového lékařství UK 1. LF a VFN, Praha přednosta prof. MUDr. J. Zeman, DrSc. 1;  Ústav farmakologie, Lékařská fakulta Univerzity Karlovy, Hradec Králové přednosta doc. MUDr. S. Mičuda, Ph. D. 2;  Ústav lékařské biofyziky, Lékařská fakulta Univerzity Karlovy, Hradec Králové přednosta doc. Ing. J. Hanuš, Ph. D. 3;  Dětská klinika Fakultní nemocnice, Hradec Králové přednosta prof. MUDr. M. Bayer, CSc. 4
Published in: Čes-slov Pediat 2013; 68 (4): 219-233.
Category: Original Papers


The aim of the study was to predict dosing with gentamicin (Ge) of which the effect is dependent on plasma concentrations (Cpl) more than on dosage, to achieve the target range of steady state through Cpl: Ctrough,3 (0.5–2.0 mg/l) and peak Cpeak,4 (5.0–10.0 mg/l), i.e. 0.5 h before the fourth and one h after the start of the fourth dose. Cpeak,4 determines bactericidal effect, Ctrough,3 predicts neurotoxicity and nephrotoxicity.

The analysis was performed by Ge fluorescence polarization immunoassay; Abbott Laboratories, Abbott Park Illinois). Fitting the parameters in a two-compartment model with four Cpl Ge were estimated: volume of distribution (Vd1) and clearance (Cl1) by the MW-Pharm 3.15 (Mediware, Groningen, NL). If the simulation of Cpl with standard dosing (4 mg/kg/24–48 h according to GV and birth weight) did not achieve the target Cpl, the standard dosing after the second dose was changed according to the estimated kinetic parameters, Ctrough,3 and Cpeak,4, and verified by ongoing analysis.

In 54 newborns (32 very low preterm, gestational age below 34 weeks and 22 low preterm GA <38 weeks) Cpeak,1 (after the first infusion) reached the target range in 80% Ctrough,1 <2 mg/l in all newborns. The standard dosing was adjusted in 85% of them, mainly by decreasing the rate of infusion or do you mean number of dosages per 24 hours (65%). The target Cpeak,4 was reached in 69% of very low preterm and 68% of low preterm newborns, Cpeak,4 <5 mg/l was reached in 31% of very low preterm and 32% of low preterm newborns. The target Ctrough,3 was obtained in all except one subject. The difference of the predicted and verified Cpeak,4 was caused by retention of fluids between the first and the fourth infusion of Ge. In case of persistent ductus arteriosus it reached up to +374.0 (45.1) ml/kg.

Kinetically guided therapy with Ge in septic newborns in the first week of life based on the Cpl after the first infusion is recommended in very low preterm newborns especially. In order to reach bactericidal Cpeak,4 the decision should be based on retention of fluids, accompanying the critical condition.

Key words:
newborn, sepsis, gentamicin, kinetically guided therapy, persistent ductus arteriosus G.


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