120 However, the treatment duration employed in this study (5 days every 28 days for 9–12 cycles) may have been suboptimal in a population of patients with chronic infection. 121 Ongoing and future trials will inform us if inhaled antibiotics are a useful therapeutic option in the prevention of exacerbations

of COPD. Acute, efficacious antibiotic Raf inhibitor treatment is the mainstay in the management of patients with severe COPD and symptomatic exacerbations that include at least 2 of the 3 cardinal symptoms (increased sputum purulence, volume and increased dyspnoea; Anthonisen type I or II exacerbations). Although such treatment is associated with clinical benefit, treatment failure and relapse rates may Regorafenib solubility dmso be high in patients with the frequent exacerbator phenotype. Failure may be related to inadequate antibiotic efficacy through incomplete resolution of the initial exacerbation and persistent bacterial infection.23, 24, 25 and 26 These factors have led to recommendations for a stratified approach to antibiotic therapy based on patient risk factors.15 Patients at greatest risk for poorer outcome (i.e. those with complicated COPD) are likely to derive greatest benefit from early treatment with the most potent antibiotic therapy, such as amoxicillin/clavulanate and respiratory fluoroquinolones which

have a broad spectrum of activity against likely pathogens.28, 122, 123 and 124 The use of the most efficacious antibiotics in patients

with risk factors may be crucial in preventing relapses or delaying subsequent exacerbations which appear to cluster in time, and if the exacerbation Cell press is poorly controlled there is a high risk of the next episode occurring within a few weeks.30 A significant relationship exists between bacterial eradication at the end of antibiotic treatment and no relapse in the following eight weeks.28 Studies conducted in the last 20 years suggest that long-term or intermittent antibiotic therapy may have a beneficial effect on the outcome of COPD patients and may improve quality of life by reducing exacerbation frequency and hospitalisations for exacerbations, or by extending time to next exacerbation. The mechanisms underlying such improvements are unclear. It is possible that the benefit of long-term antibiotic treatment may be due to a reduction in the frequency of exacerbations due to eradication of colonising potentially pathogenic bacteria and/or reduction in chronic airway inflammation,37 though the evidence supporting such a hypothesis is limited. While macrolides are known to have both antibacterial and anti-inflammatory effects, it is unknown to what degree these actions are responsible for their efficacy when used for the treatment of chronic respiratory conditions.