Level 1: Likely reliable evidence

The guideline from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) does not recommend antibiotics for prevention of COPD exacerbations. Citing decades-old data on the lack of efficacy of tetracyclines or penicillin, the guideline states that there is no benefit to the use of continuous antibiotics for prophylaxis. However, in more recent research, both moxifloxacin (Respir Res. 2010;11:10) and erythromycin (Am J Respir Crit Care Med. 2008;178:1139-47) have been associated with reduced exacerbation frequency.

Now, a new randomized trial provides strong evidence that azithromycin reduces exacerbations and improves respiratory function in high-risk patients (N Engl J Med. 2011;365:689-698). A total of 1,142 patients (mean age 66 years) with COPD were randomized to azithromycin 250 mg daily vs. placebo for one year. Most of the patients (83%) had been previously treated with systemic cortico­steroids for acute exacerbation, and 58% used long-term oxygen. Patients with (or at risk for) prolonged QTc interval were excluded, as were patients with asthma or with hearing impairment at baseline

Azithromycin significantly reduced the frequency of exacerbations (1.48 vs. 1.83 per patient-year, P<0.01), and increased the median time to first exacerbation (266 days vs. 174 days, P<0.001). Acute exacerbations occurred in 57% of the azithromycin group and in 68% of controls. The azithromycin group was also more likely to show clinically significant improvement in respiratory function scores (defined as a four-point or greater decrease on a 100-point scale) (43% vs. 36%, P=0.03, NNT=15).

Azithromycin was associated with increased risk of hearing loss (25% vs. 20%, P=0.04, NNH=20). There were no significant differences in hospitalizations for any cause, hospitalizations related to COPD or intubation rates.