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