Assessment of the Effects of a High Amikacin Dose on Plasma Peak Concentration in Critically Ill Children.

Abstract

This study aimed to assess the incidence of amikacin plasma peak concentration (Cmax) below 60 mg·L-1 in critically ill children receiving an amikacin dosing regimen of 30 mgkg-1·day-1. Secondary objectives were to identify factors associated with low Cmax and to assess the incidence of acute kidney injury (AKI). A retrospective observational study was performed in two French pediatric intensive care units. All admitted children who received 30 mg·kg-1 amikacin and had a Cmax measurement were eligible. Clinical and biological data, amikacin dose, and concentrations were collected. In total, 30 patients were included, aged from 3 weeks to 7 years. They received a median amikacin dosage of 30 mgkg-1·day-1 (range 29-33) based on admission body weight (BW), corresponding to 27 mgkg-1·day-1 (range 24-30) based on actual BW. Cmax was < 60 mg·L-1 in 21 (70%) children and none had a Cmax ≥ 80 mg·L-1. Among the 15 patients with a measured minimum inhibitory concentration (MIC), 13 (87%) had a Cmax/MIC ratio > 8. Univariate analysis showed that factors associated with Cmax < 60 mg·L-1 were high estimated glomerular filtration rate (p = 0.015) and low blood urea concentration (p = 0.001). AKI progression or occurrence was observed after amikacin administration in two (7%) and six (21%) patients, respectively. Despite the administration of the maximal recommended amikacin dose, Cmax was below the pharmacokinetic target in 70% of our pediatric population. Further studies are needed to develop a pharmacokinetic model in a population of critically ill children to optimize target attainment.