There remains controversy when instituting long-term antibiotics about whether a macrolide, an inhaled antibiotic, or a combination of both should be chosen to reduce the risk of exacerbations. Even though there are no inhaled antibiotics licensed for reducing exacerbations in patients with bronchiectasis, use in UK and European cohorts varies between 7% and 10% of patients (US rates have not been reported)., Inhaled antibiotic therapy has the benefit of targeting therapy to the site of infection. In addition, it allows higher concentrations of antibiotics in comparison with IV antibiotic therapy and may therefore work in patients with apparent resistance patterns seen from in vitro sensitivity testing.,, Two published studies of IV formulations prepared for inhalation support the hypothesis for their use and showed a reduction in exacerbations as well as improvements in other clinical end points., Treatment for 6 months or longer showed that inhaled colistin 1 mU twice daily for 6 months continuously in patients chronically infected with P. aeruginosa prolonged the time to the next exacerbation in patients who adhered to their therapy 80% of the time or more. In a single-blind study, long-term nebulized gentamicin over 1 year (80 mg twice daily) in patients chronically infected with any potential pathogenic organism and having two or more exacerbations annually improved time to the next exacerbation and reduced overall exacerbations. There was also improved bacterial clearance, sputum color, health-related quality of life, and exercise tolerance., However, a benefit-to-risk assessment is required, and side effects include bronchospasm, which occurs in about 10% of patients treated with inhaled aminoglycosides despite a negative challenge test to the inhaled antibiotic. Another issue is the high cost of inhaled antibiotics vs macrolide therapy. Macrolide therapy also has the benefit of ease of administration.,,,, There is no evidence to date about the safety and efficacy of combined macrolide and inhaled antibiotics, although combination therapy is common in patients with cystic fibrosis and chronic P. aeruginosa infection. More research is needed to understand the benefit-risk ratio of each of these treatment approaches before recommendations for appropriate use can be given.