Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients |
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Authors: | Zoe E Athanassa Sophia L Markantonis Marina-Zoe F Fousteri Pavlos M Myrianthefs Eleni G Boutzouka Athanassios Tsakris George J Baltopoulos |
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Institution: | 1. Intensive Care Unit “KAT” University Hospital, School of Nursing, University of Athens, Athens, Greece 2. Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Athens, Athens, Greece 3. Department of Microbiology, Medical School, University of Athens, Athens, Greece
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Abstract: | Purpose The purpose of this study was to describe inhaled colistin pharmacokinetics in patients with ventilator-associated tracheobronchitis (VAT) due to polymyxin-only susceptible Gram-negative bacteria (GNB). Methods Inhaled colistimethate sodium (CMS) was administered at a dose of 80?mg every 8 h for 7 days. Mini bronchoalveolar lavage (BAL) was performed before and at 1, 4 and 8 h, while blood samples were collected before and at 0.16, 0.5, 1, 2, 4 and 8 h after the first dose. Colistin concentrations in BAL and serum were determined by high-performance liquid chromatography. Results Our study population included 20 patients. At the end of treatment, cure was achieved in 16 patients and favorable microbiological response in 12 patients. Median (25–75 % interquartile range) colistin concentrations in epithelial lining fluid (ELF) were 6.7 (4.8–10.1), 3.9 (2.5–6.0) and 2.0 (1.0–3.8)?μg/ml at 1, 4 and 8 h, respectively, and fivefold higher than those achieved in serum. Median ELF concentrations at 1 and 4 h were above the minimum inhibitory concentrations of all isolated pathogens; however, the 4-h median was below the European Committee on Antimicrobial Susceptibility Guidelines (EUCAST) breakpoints for Pseudomonas aeruginosa and the 8-h median was low relative to EUCAST breakpoints for all GNB. Colistin pharmacokinetic/pharmacodynamic parameters in ELF were associated with favorable microbiological response at the end of treatment. Conclusion Inhaled colistin may achieve high drug concentrations in the lung. However, a dose of 80?mg of inhaled CMS every 8 h may not be adequate for the treatment of lower respiratory tract infections due to multi-drug resistant GNB. |
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