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Pharmacokinetic evaluation of intravenous colistin following two different dose regimens in multidrug-resistant infections

Abstract number: O516

Cusato M., Imberti R., Villani P., Carnevale L., Iotti G., Accetta G., Langer M., Regazzi M.

Objectives: Infections caused by multidrug-resistant Gram-negative bacteria are a growing clinical problem and are associated with significant morbidity and mortality. We evaluated colistin concentrations at steady-state in plasma samples and bronchoalveolar lavage (BAL) of critically ill patients admitted to our ICU.

Methods: Nineteen patients (16M, 3F) aged 20–70 years and affected with ventilator-associated pneumonia were enrolled. Six patients received 1 million IU of colistin methanesulphonate (CMS) intravenously every 6 hours; thirteen patients received 2 million IU every 8 hours for at least 2 days. Blood samples were collected from each patient at baseline (predose) and at time intervals after the end of CMS infusion. BAL was performed in all patients at 2 hours post-infusion. Colistin plasma and bronchoalveolar concentrations were measured using a selective and sensitive high performance liquid chromatography assay with fluorescence detector. Pharmacokinetic parameters were determined by non-compartmental analysis using Innaphase Kinetica™ 4.0 software.

Results: Patients receiving 1M IU/6 h had mean [±SD] Cmax and Cmin plasma concentrations at the steady-state of 1.57 [±0.57] and 1.10 [±0.43] mg/ml, respectively. Mean [±SD] AUC(0–6 h), t1/2 and Vd were 6.40 [±2.32] mg·h/ml, 8.36 [±4.94] h, and 220.46 [±76.61] L/h, respectively. Patients receiving 2M IU/8 h had mean [±SD] plasma Cmax and Cmin levels at steady-state of 2.21 [±1.08] and 0.98 [±0.70] mg/ml, respectively. Mean [±SD] AUC(0–8 h), t1/2 and Vd were 11.54 [±6.20] mg·h/ml, 5.87 [±2.56] h, and 143.24 [±116.47] L/h, respectively. Cmax/MIC and AUC(0–24 h) /MIC ratios (MIC = 2 mg/ml) were 0.79 [±0.28] and 12.79 [±4.65], 1.1 [±0.54] and 17.30 [±9.30], after administration of 1M IU and 2M IU, respectively.

Colistin was undetectable in BAL under both regimens. A complete eradication of bacteria was observed in 12/13 of our patients with the 2M IU/8 h dosing schedule.

Conclusions: In critically ill patients, the 2M IU/8 h dose regimen provided higher Cmax and AUC than the 1M IU/6 h schedule: this may be a therapeutic advantage because the AUC/MIC and Cmax/MIC ratios are strongly associated with efficacy. Further studies are needed to provide important clinical answers, from individualising treatment to optimising dosage and reducing adverse effects.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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