Does prophylactic azithromycin reduce the number of COPD exacerbations or hospitalizations?
EVIDENCE-BASED ANSWER:
Yes for exacerbations, no for hospitalizations. Prophylactic azithromycin reduces the number of exacerbations by about 25%. It also extends the time between exacerbations by approximately 90 days for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Azithromycin benefits patients who are >65 years, patients with Global Initiative for Obstructive Lung Disease (GOLD) stage II or III COPD, former smokers, and patients using long-term oxygen; it doesn’t benefit patients ≤65 years, patients with GOLD stage IV COPD, current smokers, or patients not using oxygen (strength of recommendation [SOR]: B, randomized controlled trials [RCTs]).
Prophylactic azithromycin doesn’t reduce hospitalizations overall (SOR: B, single small RCT).
Smaller study shows similar results
A smaller RCT of 92 patients that evaluated exacerbation rates with azithromycin and placebo recruited patients with at least 3 acute COPD exacerbations in the previous year.3
Compared with placebo, oral azithromycin 500 mg 3 times a week (Monday, Wednesday, and Friday) increased the time between exacerbations over a 12-month period (59 days vs 130 days; P=.001). It also reduced the exacerbation rate per person per year (1.94 vs 3.22; risk ratio=0.60; 95% CI, 0.43-0.84) but didn’t change the hospitalization rate (odds ratio=1.34; 95% CI, 0.67-2.7).
No difference in serious adverse events was found between the azithromycin and placebo groups (3 patients vs 5 patients; P=NS), but an increase in diarrhea (9 patients vs 1 patient; P=.015) was noted.
RECOMMENDATIONS
An evidence-based guideline by the American College of Chest Physicians and Canadian Thoracic Society recommends long-term macrolide therapy to prevent acute exacerbations in patients >40 years with moderate or severe COPD and a history of ≥1 moderate or severe exacerbation in the previous year despite maximized inhaler therapy (Grade 2A, weak recommendation, high-quality evidence).4 The guideline also states that the duration and optimal dosages are unknown.
