Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations.

Details

Serval ID
serval:BIB_2DD56A53FB50
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations.
Journal
Antimicrobial agents and chemotherapy
Author(s)
van Donge T., Pfister M., Bielicki J., Csajka C., Rodieux F., van den Anker J., Fuchs A.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Publication state
Published
Issued date
04/2018
Peer-reviewed
Oui
Volume
62
Number
4
Pages
e02004-17
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Optimal dosing of gentamicin in neonates is still a matter of debate despite its common use. We identified gentamicin dosing regimens from eight international guidelines and seven Swiss neonatal intensive care units. The dose per administration, the dosing interval, the total daily dose, and the demographic characteristics between guidelines were compared. There was considerable variability with respect to dose (4 to 6 mg/kg), dosing interval (24 h to 48 h), total daily dose (2.5 to 6 mg/kg/day), and patient demographic characteristics that were used to calculate individualized dosing regimens. A model-based simulation study in 1071 neonates was performed to determine the achievement of efficacious peak gentamicin concentrations according to predefined MICs (C <sub>max</sub> /MIC ≥ 10) and safe trough concentrations (C <sub>min</sub> ≤ 2 mg/liter) with recommended dosing regimens. MIC targets of 0.5 and 1 mg/liter were used. Dosing optimization was performed giving priority to the first day of treatment and with the goal of simplifying dosing. Current gentamicin neonatal guidelines allow to achieve effective peak concentrations for MICs ≤ 0.5 mg/liter but not higher. Model-based simulations indicate that to attain peak gentamicin concentrations of ≥10 mg/liter, a dose of 7.5 mg/kg should be administered using an extended dosing interval regimen. Trough concentrations of ≤2 mg/liter can be maintained with a dosing interval of 36 to 48 h in neonates according to gestational and postnatal age. For treatment beyond 3 days, therapeutic drug monitoring is advised to maintain adequate serum concentrations.
Keywords
Aminoglycosides/administration & dosage, Aminoglycosides/therapeutic use, Anti-Bacterial Agents/administration & dosage, Anti-Bacterial Agents/therapeutic use, Drug Administration Schedule, Drug Monitoring, Gentamicins/administration & dosage, Gentamicins/therapeutic use, Gestational Age, Humans, Infant, Infant, Newborn, Intensive Care Units, Neonatal, Microbial Sensitivity Tests, MIC, aminoglycosides, pediatrics, pharmacokinetics
Pubmed
Web of science
Open Access
Yes
Create date
27/01/2018 12:46
Last modification date
20/08/2019 14:12
Usage data