Chronic bacterial infection and inflammation is seen in bronchiectasis as a result of impaired clearance of the lower airways. Frequent infectious exacerbations have a major adverse impact on lung function, morbidity and quality of life.
The purpose of the current study was to determine whether use of maintenance low-dose macrolide therapy (400mg erythromycin ethylsuccinate [equivalent to 250mg erythromycin base] twice daily) for 48 weeks, in addition to standard treatment, could reduce the frequency of exacerbations in adults with non-CF bronchiectasis, who had at least two pulmonary exacerbations requiring antibiotic treatment during the preceding year. The annualised mean rate of pulmonary exacerbations (primary endpoint) was lower with erythromycin than with placebo (1.29 vs. 1.97, respectively; P =0.003) and improvements were noted in various secondary endpoints, including sputum production and lung function.
The maintenance therapy appeared to be well tolerated, although the study was not powered for toxicity. No statistically significant improvements in quality of life (as measured by the St George’s Respiratory Questionnaire) were noted; this may however be due to a lack of sensitivity of the questionnaire in this population, coupled with a lack of power for this endpoint.
Although there was no difference in microbiological profile between erythromycin- and placebo-treated patients at baseline and the end of treatment, suggesting that macrolide treatment did not result in the emergence of new pathogens, erythromycin significantly increased the proportion of macrolide-resistant commensal oropharyngeal streptococci. The authors comment that this finding should ‘curb enthusiasm for its widespread application’.
An editorial discusses the results of both this study and another study published in the same issue of the journal, which looks at azithromycin maintenance in similar patients (BAT study). The authors comment that the benefits of long-term macrolide maintenance for individual patients with bronchiectasis need to be balanced with increasing concerns over the development of resistance to both macrolides and other antibiotics among airway microbiota.