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Optimal gentamicin therapy in preterm neonates includes loading doses and early monitoring
B T Isemann1, U R Kotagal, S M Mashni
1Department of Pharmacy Services, University Hospital, Cincinnati, Ohio 45267-0740, USA.
Insights
A standard 2.5 mg/kg gentamicin dose is insufficient for neonates. A higher 4 mg/kg loading dose, with monitoring, optimizes gentamicin therapy and achieves therapeutic serum gentamicin concentrations (SGC) in newborns.
Area of Science:
- Neonatal pharmacology
- Antibiotic dosing optimization
- Pharmacokinetics in pediatrics
Background:
- Standard gentamicin dosing (2.5 mg/kg) in neonates may be inadequate.
- There is a need for optimized gentamicin dosing strategies in newborns.
- Gentamicin disposition changes significantly during the first week of life.
Purpose of the Study:
- To compare peak and trough serum gentamicin concentrations (SGC) in neonates receiving standard (2.5 mg/kg) versus loading (4 mg/kg) doses.
- To evaluate the utility of two SGC measurements after the first dose for individualized gentamicin regimens.
Main Methods:
- Prospective, randomized study of 40 neonates in the NICU.
- Randomization to receive either 2.5 mg/kg or 4 mg/kg gentamicin.
- Determination of individual gentamicin pharmacokinetic parameters after the first dose.
Main Results:
- Only 6% of neonates on 2.5 mg/kg achieved peak SGC > 5 mcg/ml, versus 94% on 4 mg/kg.
- Initial trough SGC < 2 mcg/ml occurred in 100% of neonates on 2.5 mg/kg, vs. 39% on 4 mg/kg.
- Two SGC measurements predicted steady-state peaks and troughs in 13/16 and 14/16 infants, respectively.
Conclusions:
- The standard 2.5 mg/kg gentamicin dose results in sub-therapeutic initial peak SGC in neonates.
- A 4 mg/kg gentamicin loading dose is more effective in achieving therapeutic SGC.
- Pharmacokinetic monitoring after the first dose, alongside a loading dose, optimizes neonatal gentamicin therapy.
Abstract:
Recent studies have suggested the inadequacy of an initial gentamicin 2.5 mg/kg standard dose in neonates and the need for a loading dose. The purpose of this prospective, randomized study was to compare initial peak and initial trough serum gentamicin concentrations (SGC) in neonates after a standard dose (2.5 mg/kg) or a loading dose (4 mg/kg) on the first day of life. A secondary objective of the study was to evaluate the use of two SGC drawn after the first dose in designing individualized dosage regimens, despite the many changes in gentamicin disposition that occur over the first week of life. Forty infants admitted to the NICU were randomized to receive either 2.5 or 4 mg/kg gentamicin. Individual gentamicin pharmacokinetic parameters were determined after the first dose. Initial peak SGC were > 5 mcg/ml in only 6% of neonates receiving 2.5 mg/kg, versus 94% of neonates receiving 4 mg/kg. The initial trough after the first dose was < 2 mcg/ml in 100% of patients receiving 2.5 mg/kg and only 39% of patients receiving 4 mg/kg. Using two SGC after the first dose successfully predicted steady state peaks in 13/16 infants and steady state troughs in 14/16 infants. Thus, standard treatment of 2.5 mg/kg gentamicin yields initial peak serum gentamicin concentrations < 5 mcg/ml in neonates while a 4 mg/kg gentamicin loading dose, combined with pharmacokinetic monitoring after the first dose, optimizes gentamicin therapy in neonates.