Prophylactic Azithromycin Reduces COPD Exacerbations in High-Risk Patients

DynaMed Weekly Update - Volume 6, Issue 34

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 ( GOLD report 2011 PDF). However, in more recent research, both moxifloxacin (Respir Res 2010 Jan 28;11:10) and erythromycin (Am J Respir Crit Care Med 2008 Dec 1) 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 (level 1 [likely reliable] evidence). A total of 1,142 patients (mean age 66 years) with COPD were randomized to azithromycin 250 mg daily vs. placebo for 1 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 68% of controls. The azithromycin group was also more likely to show clinically-significant improvement in respiratory function scores (defined as ? 4 point 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 (N Engl J Med 2011 Aug 25;365(8):689).

For more information, see the Acute exacerbation of COPD topic in DynaMed.