title: Inhaled colistin in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection.
abstract: BACKGROUND
  Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis.
  
  
  OBJECTIVE
  To perform a randomized placebo-controlled study assessing the efficacy and safety of inhaled colistin in patients with bronchiectasis and chronic P. aeruginosa infection.
  
  
  METHODS
  Patients with bronchiectasis and chronic P. aeruginosa infection were enrolled within 21 days of completing a course of antipseudomonal antibiotics for an exacerbation. Participants were randomized to receive colistin (1 million IU; n = 73) or placebo (0.45% saline; n = 71) via the I-neb twice a day, for up to 6 months.
  
  
  RESULTS
  The primary endpoint was time to exacerbation. Secondary endpoints included time to exacerbation based on adherence recorded by the I-neb, P. aeruginosa bacterial density, quality of life, and safety parameters. All analyses were on the intention-to-treat population. Median time (25% quartile) to exacerbation was 165 (42) versus 111 (52) days in the colistin and placebo groups, respectively (P = 0.11). In adherent patients (adherence quartiles 2-4), the median time to exacerbation was 168 (65) versus 103 (37) days in the colistin and placebo groups, respectively (P = 0.038). P. aeruginosa density was reduced after 4 (P = 0.001) and 12 weeks (P = 0.008) and the St. George's Respiratory Questionnaire total score was improved after 26 weeks (P = 0.006) in the colistin versus placebo patients, respectively. There were no safety concerns.
  
  
  CONCLUSIONS
  Although the primary endpoint was not reached, this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection. Clinical trial registered with http://www.isrctn.org/ (ISRCTN49790596).
authors.affiliation: 1 Cambridge Centre for Lung Infection and.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Haworth
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Foweraker
authors.forename: Peter
authors.initials: P
authors.lastname: Wilkinson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kenyon
authors.forename: Diana
authors.initials: D
authors.lastname: Bilton
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001987:Bronchiectasis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D002908:Chronic Disease; D003091:Colistin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D011788:Quality of Life; D012426:Russia; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014455:Ukraine; D006113:United Kingdom
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin