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

Paediatr Drugs. 2021 Jul;23(4):395-401. doi: 10.1007/s40272-021-00456-0. Epub 2021 Jun 18.

Abstract

Objectives: 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 mg kg-1·day-1. Secondary objectives were to identify factors associated with low Cmax and to assess the incidence of acute kidney injury (AKI).

Methods: 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.

Results: In total, 30 patients were included, aged from 3 weeks to 7 years. They received a median amikacin dosage of 30 mg kg-1·day-1 (range 29-33) based on admission body weight (BW), corresponding to 27 mg kg-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.

Conclusions: 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.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / diagnosis
  • Amikacin / administration & dosage*
  • Amikacin / adverse effects
  • Amikacin / blood*
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / blood*
  • Body Weight / drug effects
  • Body Weight / physiology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Critical Illness / therapy*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Microbial Sensitivity Tests / methods
  • Retrospective Studies

Substances

  • Anti-Bacterial Agents
  • Amikacin