Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial.

Abstract

IMPORTANCE:

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.

DESIGN, SETTING, AND PARTICIPANTS:

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.

INTERVENTIONS:

Azithromycin (250 mg daily) or placebo for 12 months.

MAIN OUTCOME MEASURES:

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 AND RELEVANCE:

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.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00415350.

• Authors: Josje Altenburg, Casper S de Graaff, Ymkje Stienstra, Jacobus H Sloos, Eric H J van Haren, Ralph J H Koppers, Tjip S van der Werf, Wim G Boersma
• Journal: JAMA (JAMA) Vol. 309 Issue 12 Pg. 1251-9 (Mar 27 2013) ISSN: 1538-3598 [Electronic] United States
• PMID: 23532241 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Biomarkers
• Azithromycin

Topics

• Adult
• Aged
• Anti-Bacterial Agents (adverse effects, therapeutic use)
• Azithromycin (adverse effects, therapeutic use)
• Bacterial Infections (etiology, prevention & control)
• Biomarkers (blood)
• Bronchiectasis (complications)
• Double-Blind Method
• Drug Resistance, Bacterial
• Female
• Humans
• Inflammation
• Lung (physiopathology)
• Male
• Middle Aged
• Quality of Life
• Respiratory Function Tests
• Respiratory Tract Infections (etiology, prevention & control)
• Sputum (microbiology)