Low-dose macrolide antibiotics given for 12 months significantly reduced pulmonary exacerbations in non–cystic fibrosis bronchiectasis, according to findings from two randomized, controlled trials.
However, antibiotic resistance concerns could temper the use of such an approach in clinical practice, the studies’ investigators cautioned.
In BLESS (Bronchiectasis and Low-Dose Erythromycin Study), the annualized mean rate of pulmonary exacerbations per patient per year was 1.29 in patients treated with erythromycin, compared with 1.97 in those given placebo (P = .003) (JAMA 2013;309:1260-7).
In the BAT (Bronchiectasis and Long-Term Azithromycin Treatment) study, the median number of exacerbations after 1 year was 0 in azithromycin-treated patients, compared with 2 in patients given placebo (P less than .001) (JAMA 2013;309:1251-9).
Both studies’ findings are consistent with those of the EMBRACE trial published last year (Lancet 2012;380:660-77), which showed a 500 mg-dose of azithromycin given for 6 months reduced the incidence of pulmonary exacerbations, compared with placebo, in patients who had at least one exacerbation in the past year.
"The BLESS and BAT trials provide robust evidence for a beneficial effect of long-term macrolide maintenance therapy in patients with bronchiectasis," observed Dr. J. Stuart Elborn and Michael Tunney, Ph.D., in an editorial accompanying the articles (JAMA 2013;309:1295-6).
"Given the paucity of evidence for treatments in bronchiectasis, the results of these studies and the recently published EMBRACE trial are welcome, because they provide a good evidence base for an effective therapy for bronchiectasis," added the commentators, both of Queen’s University Belfast, U.K.
Bronchiectasis is characterized by widening of the airways – specifically, the small and medium-size bronchi – mucosal thickening, and bronchial inflammation. Sufferers are usually dogged by a chronic cough and sputum production, impaired lung function, and infection-related exacerbations.
BLESS was a single-center trial conducted in Australia involving 117 outpatients with a history of two or more infective exacerbations in the past year. Patients were treated with twice-daily erythromycin (400 mg) or placebo. The mean ages of antibiotic- and placebo-treated patients were 61.1 years and 63.5 years, respectively.
Treatment with erythromycin resulted in a 43% relative reduction in the mean annualized exacerbation rate. Exacerbations also were significantly decreased in a pre-specified subgroup of patients with Pseudomonas aeruginosa airway infection.
Furthermore, "erythromycin reduced 24-hour sputum production and attenuated lung function," wrote Dr. David Serisier and his colleagues at Mater Adult Hospital in South Brisbane, Australia.
The BAT study was conducted in 14 Dutch hospitals and involved 83 outpatients with a history of three or more lower respiratory tract infections in the past year. Patients were randomized to a daily dose of 250 mg azithromycin or placebo. The mean ages of antibiotic- and placebo-treated patients were 59.9 years and 64.6 years, respectively.
The risk of patients experiencing at least one exacerbation during the trial was significantly lower if they had been treated with the antibiotic rather than being given placebo (46.5% vs. 80%, hazard ratio = 0.29).
"The number of patients needed to treat with azithromycin to maintain clinical stability was 3.0," Dr. Josje Altenburg, Medical Centre Alkmaar, the Netherlands, and associates reported. Azithromycin therapy also was associated with improved lung function, compared with placebo.
One concern with long-term treatment using these antibiotics is the possible development of macrolide resistance. Dr. Altenburg and colleagues reported a macrolide resistance rate of 88% with azithromycin, vs. 26% with placebo. In BLESS, Dr. Serisier and his coauthors observed an increased proportion of macrolide-resistant oropharyngeal streptococci, with a median increase of 27.7%, compared with 0.04% with placebo (P less than .001).
"The bacterial resistance caused by macrolide therapy mandates a cautious application of this therapy in clinical practice," Dr. Serisier and associates acknowledged. They added that the potential for resistance must "curb enthusiasm" for widespread erythromycin use.
"The benefits of long-term macrolide treatment for individual patients with bronchiectasis need to be balanced with increasing concerns regarding the development of resistance to both macrolides and other antibiotics among airway microbiota," Dr. Elborn and Dr. Tunney similarly observed in their accompanying editorial.
"Further long-term studies are required to better determine the relationship between maintenance macrolide treatment, the airway microbiome and resistome, and clinical efficacy in patients with bronchiectasis," they cautioned.
The Mater Adult Respiratory Research Trust Fund funded the BLESS trial. Dr. Serisier reported receiving honoraria, speaker fees, or travel support from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Pharmaxia, and Phebra. The BAT trial was supported by a research grant from the Foreest Medical School, Alkmaar, the Netherlands, and an unrestricted research grant from GlaxoSmithKline. Teva Netherlands provided the azathioprine tablets. Dr. Altenburg, Dr. Elborn, and Dr. Tunney had no disclosures.