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01-11-2012 | Original

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

Authors: Zoe E. Athanassa, Sophia L. Markantonis, Marina-Zoe F. Fousteri, Pavlos M. Myrianthefs, Eleni G. Boutzouka, Athanassios Tsakris, George J. Baltopoulos

Published in: Intensive Care Medicine | Issue 11/2012

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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Title: Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients
Authors: Zoe E. Athanassa
Sophia L. Markantonis
Marina-Zoe F. Fousteri
Pavlos M. Myrianthefs
Eleni G. Boutzouka
Athanassios Tsakris
George J. Baltopoulos
Publication date: 01-11-2012
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 11/2012
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-012-2628-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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