Long-term macrolide maintenance therapy in non-CF bronchiectasis: evidence and questions

Macrolide antibiotics have anti-inflammatory and immunomodulatory properties in addition to antibacterial activity. Until recently, only a small number of studies evaluating macrolides in patients with non-cystic fibrosis (CF) bronchiectasis had been published. These were open-label, uncontrolled, short-duration studies that included small numbers of patients. However, these studies suggested that macrolides can reduce exacerbation frequency, reduce sputum volume, and improve lung function in patients with non-CF bronchiectasis. Three recently published randomised, double-blind, placebo-controlled studies showed that macrolides (azithromycin or erythromycin) taken for between 6 and 12 months led to significant reductions in exacerbation rate and reduced the decline in lung function. In all studies, macrolides were generally well tolerated. The advantages of macrolide maintenance therapy need to be balanced against the risks, which include emergence of bacterial resistance, cardiotoxicity and ototoxicity. In addition, a key need is the consistent definition of endpoints for studies in non-CF bronchiectasis, particularly the definition of exacerbation, to allow systematic data analysis. Existing studies on the use of low-dose macrolides in non-CF bronchiectasis are encouraging, but further studies are needed to define the optimal agent, dose, duration for treatment, and the patients likely to benefit and long-term safety.