Skip to Main content Skip to Navigation
Journal articles

Population pharmacokinetics of single-dose amikacin in critically-ill patients with suspected ventilator-associated pneumonia

Abstract : Aims Modifications of antimicrobials’ pharmacokinetic parameters have been reported in critically ill patients, resulting in a risk of treatment failure. We characterized amikacin pharmacokinetic variability in critically ill patients with ventilator-associated pneumonia VAP) and evaluated several dosing regimens. Methods We conducted a prospective multicenter study in critically ill patients with presumptive diagnosis of Gram-negativebacilli (GNB) VAP. Patients empirically received imipenem and a single-dose of amikacin, which was administered as a 30-min infusion (20 mg/kg). Concentrations were measured 0.5, 1, 8, 16, and 24 h after beginning of infusion. Pharmacokinetic parameters were estimated using a population approach. Main pharmacodynamic target was a ratio ≥10between the concentration achieved 1 h after beginning of infusion (C1h) and the minimal inhibitory concentration of the liable bacteria (MIC).We simulated individual C1h for severaldosing regimens by Monte Carlo method and computed C1h/MIC ratios for MICs from 0.5 to 64 mg/L. Results Sixty patients (47 males), median (range) age, and body weight, 61.5 years (28–84) and 78 kg (45–126), respectively, were included. Amikacin median C1h was 45 mg/L (22–87). Mean value (between-patients variability) for CL, V1, Q, and V2 were 4.3 L/h (31 %), 15.9 L (22 %), 12.1 L/h (27 %), and 21.4 L (47 %), respectively. CL increased with CrCL (p<0.001) and V1 with body weight (p<0.001) and PaO2/FIO2 ratio (p<0.001). With a 25 mg/kg regimen, the pharmacodynamic target was achieved in 20 and 96 % for aMICs of 8 and 4 mg/L, respectively. Conclusion Amikacin clearance was decreased and its volume of distribution was increased as previously reported. A ≥25 mg/kg single-dose is needed for empirical treatment of GNB-VAP.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-01079022
Contributor : Emmanuelle Comets <>
Submitted on : Thursday, October 30, 2014 - 11:55:03 PM
Last modification on : Wednesday, August 19, 2020 - 11:18:07 AM
Long-term archiving on: : Monday, February 2, 2015 - 4:19:43 PM

Files

20140930_main_text.pdf
Files produced by the author(s)

La politique de l'éditeur de cet article ne nous permet pas de rendre visible le texte intégral immédiatement. Il sera rendu visible en dès Octobre 2015

  •  20140927_fig1.pdf    Embargoed until : jamais  Files produced by the author(s)
  •  20140927_fig2.pdf    Embargoed until : jamais  Files produced by the author(s)
  •  20140927_fig3.pdf    Embargoed until : jamais  Files produced by the author(s)
  •  20140927_fig4.pdf    Embargoed until : jamais  Files produced by the author(s)
  •  20140927_table1.pdf    Embargoed until : jamais  Files produced by the author(s)
  •  20140927_table2.pdf    Embargoed until : jamais  Files produced by the author(s)

Identifiers

Collections

Citation

Charles Burdet, Olivier Pajot, Camille Couffignal, Laurence Armand-Lefèvre, Arnaud Foucrier, et al.. Population pharmacokinetics of single-dose amikacin in critically-ill patients with suspected ventilator-associated pneumonia. European Journal of Clinical Pharmacology, Springer Verlag, 2014, pp.doi:10.1007/s00228-014-1766-y. ⟨10.1007/s00228-014-1766-y⟩. ⟨inserm-01079022⟩

Share

Metrics

Record views

515

Files downloads

902