Evaluation of Neonate-Specific Gentamicin Dosing Protocols Using a Pooled Patient Data Set: A Retrospective Analysis

Abstract

Objectives: First, to evaluate five recent gentamicin dosing protocols that are specific for neonates and determine how frequently each protocol yields desirable peak and trough concentrations. Second, to make our evaluation more robust, we included AUC as one of the pharmacokinetic parameters and compared it to traditional parameters. Finally, to evaluate a fixed dosing protocol (3 mg/kg Q24-hours) that is currently being used at one Arizona hospital (UMC). Methods: This retrospective evaluation involved datasets from three independent sources. Dataset 1 was from a previously published study, while datasets 2 and 3 were derived for this study. Datasets 1 and 2 were pooled to evaluate the five dosing protocols, while dataset 3 was used to evaluate the fixed dosing protocol used at UMC. For all subjects, demographic and laboratory data was obtained from hospital databases or charts. The data collected was used to construct pharmacokinetic values, which in turn were used in simulations with the five protocols. Dataset 3 was evaluated as a whole for frequency of desired peaks and troughs, then for subsets based on weight, gestational age, and Apgar scores. Results: Of the five evaluated, the Avent protocol yielded the fewest potentially toxic troughs. The Murphy-Carter protocol stood out in that it was the easiest to use, most universally applicable, and it yielded only slightly fewer desired troughs then the Avent protocol. AUC values proved to be a novel and exceptionally useful tool in evaluating the dosing protocols. The fixed dosing protocol used at UMC was shown to consistently produce favorable trough concentrations as a whole as well as in our subset analyses. Implications: The multitude of dosing protocols that have been offered can create confusion among health care professionals and lead to discrepancies in dosing. The primary goal of any of these protocols is to minimize the risk of toxicity while avoiding subtherapeutic doses. A dosing protocol that can consistently meet these criterion, yet offer simplicity and wide applicability, then we can come that much closer to a universal standard.