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Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients

, : Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients. Intensive Care Medicine 38(11): 1779-1786

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). Inhaled colistimethate sodium (CMS) was administered at a dose of 8 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 .16, .5, 1, 2, 4 and 8 h after the first dose. Colistin concentrations in BAL and serum were determined by high-performance liquid chromatography. Our study population included 2 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 1.1), 3.9 (2.5 6.) and 2. (1. 3.8) ?g/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. Inhaled colistin may achieve high drug concentrations in the lung. However, a dose of 8 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.


PMID: 22810779

DOI: 10.1007/s00134-012-2628-7

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