title: Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial.
abstract: OBJECTIVE
  Macrolide antibiotics have been shown beneficial in cystic fibrosis (CF) and diffuse panbronchiolitis, and earlier findings also suggest a benefit in non-CF bronchiectasis.
  
  
  OBJECTIVE
  To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis.
  
  
  METHODS
  The BAT (Bronchiectasis and Long-term Azithromycin Treatment) study, a randomized, double-blind, placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherlands among 83 outpatients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year.
  
  
  METHODS
  Azithromycin (250 mg daily) or placebo for 12 months.
  
  
  METHODS
  Number of infectious exacerbations during 12 months of treatment. Secondary end points included lung function, sputum bacteriology, inflammatory markers, adverse effects, symptom scores, and quality of life.
  
  
  RESULTS
  Forty-three participants (52%) received azithromycin and 40 (48%) received placebo and were included in the modified intention-to-treat analysis. At end of study, the median number of exacerbations in the azithromycin group was 0 (interquartile range [IQR], 0-1), compared with 2 (IQR, 1-3) in the placebo group (P < .001). Thirty-two (80%) placebo-treated vs 20 (46%) azithromycin-treated individuals had at least 1 exacerbation (hazard ratio, 0.29 [95% CI, 0.16-0.51]). In a mixed-model analysis, change in forced expiratory volume in the first second of expiration (percent of predicted) over time differed between groups (F1,78.8 = 4.085, P = .047), with an increase of 1.03% per 3 months in the azithromycin group and a decrease of 0.10% per 3 months in the placebo group. Gastrointestinal adverse effects occurred in 40% of patients in the azithromycin group and in 5% in the placebo group (relative risk, 7.44 [95% CI, 0.97-56.88] for abdominal pain and 8.36 [95% CI, 1.10-63.15] for diarrhea) but without need for discontinuation of study treatment. A macrolide resistance rate of 88% was noted in azithromycin-treated individuals, compared with 26% in the placebo group.
  
  
  CONCLUSIONS
  Among adults with non-CF bronchiectasis, the daily use of azithromycin for 12 months compared with placebo resulted in a lower rate of infectious exacerbations. This could result in better quality of life and might influence survival, although effects on antibiotic resistance need to be considered.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00415350.
authors.affiliation: Department of Pulmonary Diseases, Medical Centre Alkmaar, Wilhelminalaan 12, 1812 JD Alkmaar, The Netherlands. j.altenburg@mca.nl
authors.forename: Josje
authors.initials: J
authors.lastname: Altenburg
authors.forename: Casper S
authors.initials: CS
authors.lastname: de Graaff
authors.forename: Ymkje
authors.initials: Y
authors.lastname: Stienstra
authors.forename: Jacobus H
authors.initials: JH
authors.lastname: Sloos
authors.forename: Eric H J
authors.initials: EH
authors.lastname: van Haren
authors.forename: Ralph J H
authors.initials: RJ
authors.lastname: Koppers
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.forename: Wim G
authors.initials: WG
authors.lastname: Boersma
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D001987:Bronchiectasis / Q000150:complications*; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012129:Respiratory Function Tests; D012141:Respiratory Tract Infections / Q000209:etiology / Q000517:prevention & control*; D013183:Sputum / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D017963:Azithromycin