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

Intensive Care Med. 2012 Nov;38(11):1779-86. doi: 10.1007/s00134-012-2628-7. Epub 2012 Jul 19.


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.

MeSH terms

  • Acinetobacter baumannii
  • Administration, Inhalation
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Bronchitis / drug therapy*
  • Bronchitis / etiology
  • Colistin / administration & dosage
  • Colistin / analogs & derivatives*
  • Colistin / pharmacokinetics
  • Drug Resistance, Multiple*
  • Female
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / etiology
  • Humans
  • Klebsiella pneumoniae
  • Male
  • Middle Aged
  • Pseudomonas aeruginosa
  • Respiration, Artificial / adverse effects*
  • Tracheitis / drug therapy*
  • Tracheitis / etiology


  • Anti-Bacterial Agents
  • colistinmethanesulfonic acid
  • Colistin