Long-term, low-dose erythromycin in bronchiectasis subjects with frequent infective exacerbations

Abstract

Macrolide antibiotics are increasingly prescribed for subjects with non-cystic fibrosis (CF) bronchiectasis, an empiric extension of their proven efficacy in CF. Widespread, injudicious use of long-acting macrolides, particularly azithromycin, risks significantly increasing population antimicrobial resistance. In an attempt to power a definitive randomised-controlled trial (RCT), an uncontrolled evaluation of the impact of long-term, low-dose oral erythromycin therapy upon pulmonary exacerbation frequency in non-CF bronchiectasis subjects was performed. Adult bronchiectasis subjects with at least 2 infective exacerbations in the preceding 12 months were followed for 12 months following commencement of prophylactic oral erythromycin 250 mgs daily. The co-primary outcome measures, comparing the 12 month erythromycin and pre-erythomycin periods, were numbers of infective exacerbations and days of antibiotic therapy for infective exacerbations. In the 24 evaluable subjects completing a minimum of 12 months of therapy, erythromycin was associated with halving of both the median (range) annual number of infective exacerbations (2 (0-8) vs. 4 (2-11), 95% CI 1.5 to 3.5, p < 0.0001) and annual days of antibiotic use (21 (0-78) vs. 44 (15-138), 95% CI 18 to 40, p < 0.0001) compared with the preceding 12 month period. Low-dose erythromycin may have a robust effect upon exacerbation frequency in non-CF bronchiectasis subjects with frequent exacerbations and this warrants proceeding to a definitive intervention study. These data have enabled powering of an RCT of long-term, low-dose erythromycin, which is now underway and also incorporates bronchoscopic evaluation for pathophysiologic data.