Effect of long-term, low-dose erythromycin on pulmonary exacerbations among
patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled
trial.
Author(s): Serisier DJ(1), Martin ML, McGuckin MA, Lourie R, Chen AC, Brain B, Biga S,
Schlebusch S, Dash P, Bowler SD.
Affiliation(s): Author information:
(1)Department of Respiratory Medicine, Level 9, Mater Adult Hospital, Raymond Terr,
South Brisbane, Queensland 4101, Australia. david.serisier@mater.org.au
Publication date & source: 2013, JAMA. , 309(12):1260-7
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.
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