title: Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial.
abstract: OBJECTIVE
  Macrolide antibiotics such as erythromycin may improve clinical outcomes in non-cystic fibrosis (CF) bronchiectasis, although associated risks of macrolide resistance are poorly defined.
  
  
  OBJECTIVE
  To evaluate the clinical efficacy and antimicrobial resistance cost of low-dose erythromycin given for 12 months to patients with non-CF bronchiectasis with a history of frequent pulmonary exacerbations.
  
  
  METHODS
  Twelve-month, randomized (1:1), double-blind, placebo-controlled trial of erythromycin in currently nonsmoking, adult patients with non-CF bronchiectasis with a history of 2 or more infective exacerbations in the preceding year. This Australian study was undertaken between October 2008 and December 2011 in a university teaching hospital, with participants also recruited via respiratory physicians at other centers and from public radio advertisements.
  
  
  METHODS
  Twice-daily erythromycin ethylsuccinate (400 mg) or matching placebo.
  
  
  METHODS
  The primary outcome was the annualized mean rate of protocol-defined pulmonary exacerbations (PDPEs) per patient. Secondary outcomes included macrolide resistance in commensal oropharyngeal streptococci and lung function.
  
  
  RESULTS
  Six-hundred seventy-nine patients were screened, 117 were randomized (58 placebo, 59 erythromycin), and 107 (91.5%) completed the study. Erythromycin significantly reduced PDPEs both overall (mean, 1.29 [95% CI, 0.93-1.65] vs 1.97 [95% CI, 1.45-2.48] per patient per year; incidence rate ratio [IRR], 0.57 [95% CI, 0.42-0.77]; P = .003), and in the prespecified subgroup with baseline Pseudomonas aeruginosa airway infection (mean difference, 1.32 [95% CI, 0.19-2.46]; P = .02). Erythromycin reduced 24-hour sputum production (median difference, 4.3 g [interquartile range [IQR], 1 to 7.8], P = .01) and attenuated lung function decline (mean absolute difference for change in postbronchodilator forced expiratory volume in the first second of expiration, 2.2 percent predicted [95% CI, 0.1% to 4.3%]; P = .04) compared with placebo. Erythromycin increased the proportion of macrolide-resistant oropharyngeal streptococci (median change, 27.7% [IQR, 0.04% to 41.1%] vs 0.04% [IQR, -1.6% to 1.5%]; difference, 25.5% [IQR,15.0% to 33.7%]; P < .001).
  
  
  CONCLUSIONS
  Among patients with non-CF bronchiectasis, the 12-month use of erythromycin compared with placebo resulted in a modest decrease in the rate of pulmonary exacerbations and an increased rate of macrolide resistance.
  
  
  BACKGROUND
  anzctr.org.au Identifier: ACTRN12609000578202.
authors.affiliation: Department of Respiratory Medicine, Level 9, Mater Adult Hospital, Raymond Terr, South Brisbane, Queensland 4101, Australia. david.serisier@mater.org.au
authors.forename: David J
authors.initials: DJ
authors.lastname: Serisier
authors.forename: Megan L
authors.initials: ML
authors.lastname: Martin
authors.forename: Michael A
authors.initials: MA
authors.lastname: McGuckin
authors.forename: Rohan
authors.initials: R
authors.lastname: Lourie
authors.forename: Alice C
authors.initials: AC
authors.lastname: Chen
authors.forename: Barbara
authors.initials: B
authors.lastname: Brain
authors.forename: Sally
authors.initials: S
authors.lastname: Biga
authors.forename: Sanmarié
authors.initials: S
authors.lastname: Schlebusch
authors.forename: Peter
authors.initials: P
authors.lastname: Dash
authors.forename: Simon D
authors.initials: SD
authors.lastname: Bowler
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001987:Bronchiectasis / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000209:etiology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000209:etiology / Q000517:prevention & control*; D013183:Sputum / Q000382:microbiology; D013291:Streptococcus / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin