Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial

JAMA. 2013 Mar 27;309(12):1260-7. doi: 10.1001/jama.2013.2290.


Importance: 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.

Design, setting, and participants: 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.

Interventions: Twice-daily erythromycin ethylsuccinate (400 mg) or matching placebo.

Main outcome measures: 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).

Conclusion and relevance: 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.

Trial registration: anzctr.org.au Identifier: ACTRN12609000578202.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Bronchiectasis / complications*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Resistance, Bacterial
  • Erythromycin / administration & dosage*
  • Erythromycin / pharmacology
  • Female
  • Humans
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Pseudomonas Infections / etiology
  • Pseudomonas Infections / prevention & control
  • Pseudomonas aeruginosa / isolation & purification
  • Respiratory Tract Infections / etiology
  • Respiratory Tract Infections / prevention & control*
  • Sputum / microbiology
  • Streptococcus / isolation & purification
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Erythromycin