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

Objective To develop and validate a 48-hour gentamicin dosing regimen for infants born at <28 weeks' gestation. Study design Using previously published pharmacokinetic data, we performed Monte Carlo simulations for several candidate gentamicin dosing regimens. Oil the basis of these simulations, we changed dosing for infants horn 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 histrorical control subjects who received 2.5 mg/kg every 25 hours. Results Infants in the 48-hour group achieved higher gentamicin peaks (mean 9.43 mu g/mL vs 6.0 mu g/mL vs P < .001) and lower gentamicin troughs (mean 1.08 mu g/mL vs 1.54 mu g/mL, P < .001) and the 48-hour group infants had a gentamicin peak <6 mu g/mL, versus 43% in the 24-hour group. With a goal for peaks of 6 to 12 mu g/mL, and for troughs of <1.5 mu g/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%). Conclusions Gentamicin 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 closing in premature infants.