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.


METHODS
Using 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.


RESULTS
Infants in the 48-hour group achieved higher gentamicin peaks (mean 9.43 microg/mL vs 6.0 microg/mL, P < .001) and lower gentamicin troughs (mean 1.08 microg/mL vs 1.54 microg/mL, P < .001) compared with the 24-hour group. Seven percent of the 48-hour group infants had a gentamicin peak <6 microg/mL versus 43% in the 24-hour group. With a goal for peaks of 6 to 12 microg/mL and for troughs of <1.5 microg/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 dosing in premature infants.
Thingvoll
Erik S
ES
Department of Pediatrics, Division of Neonatology, University of Rochester Medical Center, Rochester, NY 14642, USA. ethingvoll@gmail.com
Guillet
Ronnie
R
Caserta
Mary
M
Dicenzo
Robert
R
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000517:prevention & control*; D007234:Infant, Premature; D009010:Monte Carlo Method; D018805:Sepsis / Q000517:prevention & control*
D000900:Anti-Bacterial Agents; D005839:Gentamicins