Long-term antibiotics in COPD: more benefit than harm?

261 PRIMARY CARE RESPIRATORY JOURNAL www.thepcrj. org Chronic obstructive pulmonary disease (COPD) is characterised by recurrent episodes of exacerbations defined by an acute increase in respiratory symptoms. These exacerbations are the main cause of medical visits and mortality, particularly so in severe COPD, and therefore prevention of these episodes is one of the major goals in the management of COPD. With this objective in mind, in the early 1970s some studies on the use of long-term antibiotics in patients with chronic bronchitis and frequent infective exacerbations were conducted. Most of these studies were characterised by small sample sizes and important flaws in their design. Although they showed a small reduction in exacerbations in general, a growing concern for the development of bacterial resistance emerged. With the development of new and more effective inhaled medications for COPD, this strategy of treatment was generally abandoned and no further trials were conducted until recently. Current guidelines recommend the use of long-acting bronchodilators and (corticosteroid) anti-inflammatories, together with non-pharmacologic measures such as pulmonary rehabilitation in order to prevent COPD exacerbations. However, some (or most) of these exacerbations have an infectious origin, and bronchodilators and anti-inflammatories never fully prevent these episodes in COPD patients who are chronically infected and may have associated bronchiectasis. In fact, some evidence suggests that the use of inhaled corticosteroids (ICS) might even be a risk factor for increased bacterial load in the airways of such patients, and that this relates to the observed increased risk of pneumonia. Patients with COPD may present different clinical phenotypes, and therefore not only treatment but also prevention of exacerbations may be different according to the phenotype. Those patients with frequent bacterial exacerbations characterised by dark sputum and who often have bronchiectasis when studied by computed tomography (CT) scanning constitute a particular phenotype – the “infective phenotype”. Those patients who, despite optimal management, continue to present bacterial exacerbations may require complementary treatment directed to control and (if possible) eradicate bacterial infection in the airways. The frequency of current use of long-term antibiotics for the prevention of exacerbations of COPD in clinical practice is unknown. In this issue of the PCRJ, James et al. investigated the use of this therapy in the UK through a retrospective cohort study of a large primary care database between 2000 and 2009. The results demonstrate that long term antibiotics were seldom used (only 567 patients out of 92,576; 0.61%) and interestingly tetracyclines and penicillin were the most widely used antibiotics, followed by macrolides. These results suggest that the choice of antibiotic was more influenced by the old chronic bronchitis studies than by new evidence on the use of macrolides in cystic fibrosis or bronchiectasis. However, the use of macrolides increased after 2005, which suggests an influence from more recent studies in patients with chronic respiratory diseases. Interestingly, this is the first study to provide an estimate of the prevalence of use of this type of therapy for COPD in the community, and the results indicate that the use of long-term antibiotics until 2009 in the UK was marginal. It will be interesting to see if there has been any increase after the publication of new studies with pulsed moxifloxacin or with macrolides during the last 5 years. These studies have been conducted in large, well defined populations and, in general, have provided positive results in the prevention of exacerbations when using long-term antibiotics on top of the usual medication for COPD. Despite the positive results in the prevention of exacerbations in patients with COPD, it has to be remembered that long-term treatment with antibiotics, and particularly with macrolides, is associated with significant side effects and the risk of development of bacterial resistance, affecting not only the treated patients but also adversely affecting community macrolide resistance as well. In this context it has to be considered a very positive result that only 0.61% of COPD patients in the UK were receiving this therapeutic alternative. Nevertheless, it is clear that a small subpopulation of patients with COPD may benefit from this approach. The real challenge is to provide this treatment to the right patient and prevent the excessive use of long-term antibiotics in the community. Most guidelines do not recommend the use of long-term antibiotics based on a negative evaluation of the possible benefit and harm, but they fail to consider the selected population in which benefit may clearly exceed the harm. The recent Spanish guidelines for COPD suggest that long-term treatment with macrolides can be considered in patients with severe COPD and frequent exacerbations or hospital Long-term antibiotics in COPD: more benefit than harm?