The Effects of Long-term Macrolide Therapy in COPD Patients with Frequent Exacerbations

Exacerbations of chronic obstructive pulmonary disease (COPD) have a major impact on lung function, morbidity and mortality. Macrolide antibiotics have been successfully used as maintenance treatment in several chronic inflammatory pulmonary diseases. We demonstrated that a regimen of azithromycin treatment 500 mg three times a week during one year compared to placebo, leads to a larger reduction in exacerbation frequency in COPD patients with a minimum of three exacerbations in the previous year. We investigated the role of viral infections. We found a viral infection in a quarter of exacerbations. It was found that human rhinovirus (HRV) was most prevalent with a peak in July. COPD patients with frequent exacerbations showed the best response to maintenance treatment with azithromycin in patients with the following characteristics: baseline blood eosinophil count ≥ 2.0% (compared to an eosinophil count < 2.0%), GOLD stage 1-2 (versus GOLD stage 4) and GOLD group C (compared to group D).
We determined the effect of azithromycin maintenance therapy on the dynamics of macrolide resistance genes in the pharyngeal microbiota. It was shown that the acquisition of macrolide resistance genes was limited but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo.