Determination of a gentamicin loading dose in neonates and infants

The use of gentamicin as a co-therapy for the treatment of sepsis is common practice in neonates and infants. Gentamicin dosing guidelines have been developed over the past 20 years to accommodate a slower renal elimination rate of gentamicin in the neonatal population. Recently, it has become evident that early attainment of serum gentamicin concentrations > or = 5 micrograms/ml results in a greater therapeutic outcome in septic adult patients. As neonatal immunity is immature and aminoglycosides have an extended elimination half-life in the very young population, reassessment of the initial gentamicin dose has become necessary. Using retrospective data, we determined the amount of gentamicin necessary to effectively "load" a group of neonatal/pediatric patients to achieve initial serum concentrations of 6 or 8 micrograms/ml. One hundred sixty-six patients less than 12 months postnatal age were studied. The mean initial dose delivered was 2.41 mg/kg. Younger patients demonstrated larger gentamicin apparent volumes of distribution and slower elimination half-lives than did older patients. Initial serum gentamicin concentrations calculated from steady-state pharmacokinetic parameters were significantly lower than those seen at steady state. In order to achieve initial serum gentamicin concentrations > 6 micrograms/ml an initial dose of 3 mg/kg would be necessary in the group of patients studied. Younger patients (< or = 34 weeks gestational age) would likely require 4 mg/kg as an initial dose.