Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia.
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...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 71; no. 1; pp. 75 - 84 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jan2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103866208&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103866208 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jan2015 vid: 71 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 103866208 100209207 10.1007/s00228-014-1766-y 103866208 ppf: 75 ppct: 9 formats: fmt: @attributes: type: P tig: atl: Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia. aug: au: Burdet, C. Pajot, O. Couffignal, C. Armand-Lefèvre, L. Foucrier, A. Laouénan, C. Wolff, M. Massias, L. Mentré, F. affil: V. Dupouy Hospital, Intensive Care Unit 95107 Argenteuil France sug: subj: Amikacin Administration and Dosage Amikacin Pharmacokinetics Pneumonia, Ventilator-Associated Drug Therapy Pneumonia, Ventilator-Associated Diagnosis Critically Ill Patients Human Prospective Studies Multicenter Studies Imipenem Administration and Dosage Descriptive Statistics Male Female Adult Middle Age Aged Aged, 80 and Over France Algorithms Simulations Clinical Assessment Tools Confidence Intervals Funding Source Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Male Female ab: 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-negative bacilli (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 ≥10 between the concentration achieved 1 h after beginning of infusion ( C) and the minimal inhibitory concentration of the liable bacteria (MIC). We simulated individual C for several dosing regimens by Monte Carlo method and computed C/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 C 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 PaO/FIO ratio ( p < 0.001). With a 25 mg/kg regimen, the pharmacodynamic target was achieved in 20 and 96 % for a MICs 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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