Quantitative analysis of gentamicin exposure in neonates and infants calls into question its current dosing recommendations [PublishAheadOfPrint]

Optimal dosing of gentamicin in neonates is still a matter of debate despite its common use. We identified gentamicin dosing regimens from 8 international guidelines and 7 Swiss Neonatal Intensive Care Units. Dose per administration, dosing interval, total daily dose and 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 which were used to calculate individualized dosing regimens. A model-based simulation study in 1071 neonates was performed to determine achievement of efficacious peak gentamicin concentrations according to predefined minimum inhibitory concentrations (MICs) (C_max/MIC ≥ 10) and safe trough concentrations (C_min ≤ 2 mg/L) with recommended dosing regimens. MIC targets of 0.5 and 1 mg/L 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, achieve effective peak concentrations if MIC is 0.5 mg/L but not for MICs ≥ 1 mg/L. Model-based simulations indicate that to attain peak gentamicin concentrations ≥ 10 mg/L, a dose of 7.5 mg/kg should be administered using an extended dosing interval regimen. Trough concentrations ≤ 2 mg/L can be maintained with a dosing interval of 36 to 48 hours in neonates according to gestational and postnatal age. For treatment beyond 3 days, therapeutic drug monitoring is advised to maintain adequate serum concentrations.

http://ift.tt/2E18D78