Accuracy of Empiric Gentamicin Dosing Guidelines in Neonates

Abstract

OBJECTIVE To evaluate the accuracy of a neonatal gentamicin nomogram to achieve therapeutic gentamicin serum concentrations without further adjustment, allowing for decreased serum drug monitoring METHODS Retrospective single center review of all gentamicin pharmacokinetic evaluations in patients ≤ 30 days of life from July 2005 – June 2007. Patients were evaluated for postnatal age, gestational age, weight, serum creatinine, dose/interval, serum drug peaks and troughs, results of discharge hearing test and recent use of indomethacin. Logistic regression was utilized to determine potential factors impacting overall dosing accuracy, potentially allowing for decreased therapeutic drug monitoring. Factors found to be significant were incorporated into new guidelines which were evaluated through pharmacokinetic modeling. RESULTS Overall accuracy rate was 84% when empiric dosing guidelines were utilized; 16% of all doses were changed due to supratherapeutic troughs and 1% were changed due to subtherapeutic peaks. Variables found to impact the necessity for dose changes incuded gestational age (p≤0.001), weight (p≤0.001), indomethacin use (p≤0.001), number of indomethacin doses used (p≤0.001 and p=0.009 for 1–3 and 4–6 doses, respectively), and SCr in patients ≥ 7 days old (p=0.028); however, only gestational age remained a significant predictor when all other factors were considered (p=0.008). The current guidelines were changed to account for increased troughs in patients ≤ 28 weeks gestation and examined through pharmacokinetic modeling. Pharmacokinetic modeling of the new guidelines predicted an overall accuracy of 94%. CONCLUSIONS From the data gathered regarding the accuracy in patients ≥ 35 weeks gestation, we recommend to decrease therapeutic drug monitoring within this cohort. Utilizing the results of regression analysis, the current guidelines have been adjusted to allow for increased clearance in patients ≤ 28 weeks gestation, although they still need to be prospectively evaluated.

Gentamicin Dosing in Neonates with Normal Renal Function: Trough and Peak Levels

“…There are many different neonatal gentamicin dosing regimens. These range from conventional multiple-dose/day regimens (low dose, short interval) to extended interval dosing (high dose, long interval) with doses ranging from 2.5 to 5 mg/kg given every 12 h in traditional multiple dose regimens to doses given every 24-48 h in extended interval regimens [1][2][3][4][5]. These extended interval regimens have largely been adopted, not because there is evidence that they are better, but because their use has been extrapolated from regimens used in adults and children.…”