Observational Trial of a 48-Hour Gentamicin Dosing Regimen Derived from Monte Carlo Simulations in Infants Born at Less than 28 Weeks' Gestation

ObjectiveTo develop and validate a 48-hour gentamicin dosing regimen for infants born at <28 weeks' gestation.Study designUsing previously published pharmacokinetic data, we performed Monte Carlo simulations for several candidate gentamicin dosing regimens. On the basis of these simulations, we changed dosing for infants born at <28 weeks to 4.5 mg/kg every 48 hours. We then conducted an observational study of 30 infants on this new regimen and compared serum gentamicin levels with 60 historical control subjects who received 2.5 mg/kg every 24 hours.ResultsInfants in the 48-hour group achieved higher gentamicin peaks (mean 9.43 μg/mL vs 6.0 μg/mL, P < .001) and lower gentamicin troughs (mean 1.08 μg/mL vs 1.54 μg/mL, P < .001) compared with the 24-hour group. Seven percent of the 48-hour group infants had a gentamicin peak <6 μg/mL versus 43% in the 24-hour group. With a goal for peaks of 6 to 12 μg/mL and for troughs of <1.5 μg/mL, infants in the 48-hour group required fewer adjustments of their dosing regimens compared with the 24-hour group (26.7% vs 78.3%).ConclusionsGentamicin given every 48 hours to infants born at <28 weeks achieves optimal blood concentrations more frequently than does once-daily dosing. Monte Carlo simulations on the basis of pharmacokinetic modeling are useful to optimize drug dosing in premature infants.