van Donge, T; Pfister, M; Bielicki, J; Csajka, C; Rodieux, F; van den Anker, J; Fuchs, A
(2018)
Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations.
Antimicrob Agents Chemother, 62 (4).
e02004-17.
ISSN 1098-6596
https://doi.org/10.1128/AAC.02004-17
SGUL Authors: Bielicki, Julia Anna
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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 (Cmax/MIC ≥ 10) and safe trough concentrations (Cmin ≤ 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.
Item Type: |
Article
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Additional Information: |
Copyright © American Society for Microbiology, Antimicrob. Agents Chemother. 62:e02004-17 doi: 10.1128/AAC.02004-17, 2018 |
Keywords: |
MIC, aminoglycosides, pediatrics, pharmacokinetics, aminoglycosides, pediatrics, pharmacokinetics, MIC, MIC, aminoglycosides, pediatrics, pharmacokinetics, Microbiology, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology And Pharmaceutical Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Antimicrob Agents Chemother |
ISSN: |
1098-6596 |
Language: |
eng |
Dates: |
Date | Event |
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April 2018 | Published | 21 January 2018 | Published Online | 9 January 2018 | Accepted |
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PubMed ID: |
29358294 |
Web of Science ID: |
WOS:000428392100034 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/109904 |
Publisher's version: |
https://doi.org/10.1128/AAC.02004-17 |
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