Development and Evaluation of a Nomogram for Determining Gentamicin Dosing Intervals in Neonates

Abstract

Objectives: To create a nomogram that can accurately predict dosing intervals for aminoglycoside dosing in neonates based on one concentration measurement. Methods: Pooled pharmacokinetic data from previous studies were used (n=341) to create a nomogram that would accurately predict dosing intervals for aminoglycosides. The population value for volume of distribution (0.45 L/kg) was used to formulate a nomogram to select a dosing interval for neonates that would achieve a trough concentration of < 0.5 mg/L one hour prior to the next scheduled dose. The fixed dose of 4 mg/kg was used to simulate concentration elimination profiles all neonates in the study group. The data from the study group elimination profile was then compared against the nomogram and evaluated for the number of correct dosing intervals the nomogram predicted from hour 6 to 22 at 1 hour intervals. The trough concentration cutoff was < 0.5 mg/L with neonates not achieving this concentration prior to the next dose to be deemed dosed incorrectly. The nomogram was considered to have failed at any time point where the nomogram indicated an interval that would not have achieved the desired trough concentration of < 0.5 mg/L or if the interval chosen by the nomogram was longer then necessary. Results: The simulated data from the test group showed that from 15 to 21 hours post infusion 81.0 to 92.1% of neonates had the correct interval predicted by the nomogram. Greater accuracy was achieved the longer time that elapsed before a concentration is drawn, with the greatest accuracy (92.1%) at 21 hours post infusion. However, this was close to the next dose recommending a concentration draw time at 18 hours post infusion to maximize the combination of accuracy and time remaining before the next scheduled dose. This gives the lab time to report the concentration before the next dose is scheduled and achieves an accuracy rate of 87.6%. Conclusions: The use of this nomogram is a valid tool to predict dosing intervals for aminoglycosides in neonates and can aid in saving hospital resources by needing only one concentration measurement to determine dosing interval.