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

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PK/PD targets of amikacin and gentamicin in ICU patients

A Coste1, G Deslandes2, L Jalin3

  • 1EE 1701 MIHAR, université de Nantes, 44035 Nantes, France; Service de maladies infectieuses, CHU de Brest, 29609 Brest, France.

Medecine Et Maladies Infectieuses
|December 30, 2019
PubMed
Abstract

Insights

High doses of amikacin and gentamicin achieved low initial concentrations in intensive care unit (ICU) sepsis patients. However, the Cmax/MIC ratio was adequate for susceptible pathogens, indicating potential efficacy despite suboptimal drug levels.

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Aminoglycosides like amikacin and gentamicin are crucial for treating sepsis.
  • Achieving therapeutic drug concentrations is vital for effective sepsis management in the intensive care unit (ICU).
  • Previous studies suggest variability in aminoglycoside dosing and achievement of target concentrations in critically ill patients.

Purpose of the Study:

  • To evaluate the probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) targets with amikacin and gentamicin in ICU sepsis patients.
  • To assess the initial maximum concentration (Cmax) and Cmax/MIC ratio for amikacin and gentamicin after a single dose.

Main Methods:

  • A prospective, single-center study involving 138 ICU patients with severe sepsis or septic shock.
  • Patients received either intravenous amikacin (30mg/kg) or gentamicin (8mg/kg).
  • Maximum concentration (Cmax) was measured, and PK/PD targets (Cmax and Cmax/MIC ratio) were assessed based on French guidelines.

Main Results:

  • The targeted Cmax was achieved in 59.6% of patients receiving amikacin and 2.2% receiving gentamicin.
  • An adequate Cmax/MIC ratio (≥8) was achieved in all patients infected with susceptible pathogens.
  • Dose per kg of adapted body weight and renal clearance were factors associated with achieving amikacin Cmax targets.

Conclusions:

  • Initial Cmax of amikacin and gentamicin remains low in ICU sepsis patients, even with high doses.
  • Despite low Cmax, an adequate Cmax/MIC ratio was achieved in patients with susceptible pathogens, suggesting potential therapeutic benefit.
  • Optimizing dosing based on patient-specific factors like weight and renal function is crucial for amikacin therapy.
Keywords:
AmikacinGentamicinIntensive care unitPK/PD

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