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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Assessment of the Effects of a High Amikacin Dose on Plasma Peak Concentration in Critically Ill Children

Rym Medjebeur Hanna1, Michael Levy2, Emmanuelle Bille3

  • 1Service de Réanimation et Surveillance Continue Médico-chirugicale Pédiatriques, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France.

Paediatric Drugs
|June 18, 2021
PubMed

Insights

Most critically ill children (70%) did not reach target amikacin plasma peak concentrations (Cmax) with the standard 30 mg/kg/day dose. Higher kidney function and lower blood urea were linked to sub-therapeutic amikacin levels.

Area of Science:

  • Pediatric Intensive Care
  • Pharmacokinetics
  • Infectious Diseases

Background:

  • Amikacin is a critical antibiotic for severe pediatric infections.
  • Optimizing amikacin dosing in critically ill children is essential for efficacy and safety.
  • Current dosing guidelines may not achieve therapeutic amikacin plasma peak concentrations (Cmax) in this population.

Purpose of the Study:

  • To determine the incidence of sub-therapeutic amikacin Cmax (< 60 mg·L⁻¹) in critically ill children.
  • To identify factors associated with low amikacin Cmax.
  • To assess the occurrence of acute kidney injury (AKI) in this patient group.

Main Methods:

  • Retrospective observational study in two French pediatric intensive care units.
  • Inclusion of critically ill children receiving amikacin 30 mg·kg⁻¹·day⁻¹ with Cmax measurement.
  • Collection of clinical, biological, and amikacin concentration data.

Main Results:

  • 70% (21/30) of children had amikacin Cmax < 60 mg·L⁻¹.
  • High estimated glomerular filtration rate and low blood urea concentration were associated with low Cmax.
  • Acute kidney injury (AKI) occurred in 21% of patients.

Conclusions:

  • The standard amikacin dose of 30 mg·kg⁻¹·day⁻¹ frequently fails to achieve target Cmax in critically ill children.
  • Further research is needed to develop population pharmacokinetic models for optimized amikacin dosing.
  • Individualized dosing strategies may be required to improve amikacin target attainment and patient outcomes.
Abstract

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