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Updated: Dec 13, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

13.2K

Aminoglycosides in critically ill patients: which dosing regimens for which pathogens?

A Marsot1, S Hraiech2, N Cassir3

  • 1Faculté de Pharmacie, Université de Montréal, Montréal, Canada.

International Journal of Antimicrobial Agents
|August 3, 2020
PubMed

Insights

Optimized aminoglycoside dosing regimens, including amikacin, gentamicin, and tobramycin, are crucial for critically ill patients to prevent treatment failure. Dosing adjustments based on body weight and creatinine clearance improve efficacy and safety.

Area of Science:

  • Pharmacology
  • Critical Care Medicine
  • Infectious Diseases

Background:

  • Antibiotic pharmacokinetic parameters are altered in critically ill patients, increasing the risk of treatment failure.
  • Aminoglycosides like amikacin, gentamicin, and tobramycin are essential for treating severe infections but require careful dosing.

Purpose of the Study:

  • To determine optimized intravenous dosing regimens for amikacin, gentamicin, and tobramycin in critically ill patients.
  • To improve the probability of target attainment for these antibiotics in a challenging patient population.

Main Methods:

  • A parametric population pharmacokinetic approach was used.
  • Monte Carlo simulations calculated the probability of target attainment using Cmax/MIC and trough concentrations.
  • Data from 117 critically ill patients treated with amikacin, gentamicin, or tobramycin were analyzed.

Main Results:

  • Clearance and volume of distribution varied significantly between antibiotics and patient groups (e.g., cystic fibrosis).
  • Dosing adjustments for amikacin and gentamicin should consider actual body weight and creatinine clearance.
  • Tobramycin dosing should be based on creatinine clearance and the presence of cystic fibrosis.

Conclusions:

  • Recommended initial doses: amikacin 35 mg/kg, tobramycin 10 mg/kg (CF and non-CF).
  • Gentamicin (5 mg/kg) showed optimal target attainment for Staphylococcus aureus infections.
  • Conflicting efficacy and safety targets necessitate therapeutic drug monitoring for aminoglycosides in critically ill patients.
Keywords:
AminoglycosideCritically illPopulation pharmacokineticsSimulation

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