Macrolide antibiotic decreases COPD exacerbations in select patients, study finds

Daily azithromycin for one year decreased chronic obstructive pulmonary disease (COPD) exacerbations and improved quality of life among select patients, researchers reported.

Researchers conducted a prospective, parallel-group, placebo-controlled trial of 1,142 patients age 40 years and older. Participants from 17 sites associated with 12 academic U.S. health centers were randomized to receive 250 mg of oral azithromycin or placebo daily. The study was supported by grants from the National Heart, Lung, and Blood Institute. Results appeared in the Aug. 25 issue New England Journal of Medicine.

Studied patients had a clinical diagnosis of COPD (defined as a smoking history of at least 10 pack-years, a ratio of postbronchodilator forced expiratory volume in 1 second [FEV₁] to forced vital capacity of <70%, and a postbronchodilator FEV₁ of <80% of the predicted value), were using continuous supplemental oxygen or had received systemic glucocorticoids within the previous year, had gone to an emergency department or had been hospitalized for an acute exacerbation of COPD, and had not had an acute exacerbation of COPD for at least four weeks before enrollment.

Exclusion criteria were asthma, a resting heart rate greater than 100 beats per minute, a prolonged corrected QT (QTc) interval greater than 450 ms, use of medications that prolong the QTc interval or are associated with torsades de pointes (with the exception of amiodarone), and an existing hearing impairment.

The primary outcome was the time to the first acute COPD exacerbation. A total of 1,641 acute COPD exacerbations occurred, 741 among the 558 azithromycin patients and 900 among the 559 placebo patients. The rates of acute COPD exacerbations per patient-year were 1.48 and 1.83, respectively (P=0.01; rate ratio from negative binomial analysis, 0.83; 95% CI, 0.72 to 0.95). There were fewer acute exacerbations in the azithromycin group than the placebo group regardless of the rate of acute exacerbations per patient-year (P=0.008). The number needed to treat to prevent one acute exacerbation of COPD was 2.86.

The median time to the first acute exacerbation of COPD was 266 days (95% CI, 227 to 313 days) in the azithromycin group and 174 days (95% CI, 143 to 215 days) in the placebo group (P<0.001). The hazard ratio of having an acute exacerbation of COPD per patient-year in the azithromycin group as compared with the placebo group was 0.73 (95% CI, 0.63 to 0.84; P<0.001).

Quality of life scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4; P=0.004).

There were no differences in serious adverse events between the study and control groups. An audiogram-confirmed hearing decrement occurred in 142 of the patients receiving azithromycin (25%), compared with 110 of those receiving placebo (20%) (P=0.04). But, researchers said, hearing improved with repeat testing regardless of whether the study drug was discontinued. This suggests that study criteria were too stringent and that the incidence of hearing decrements was overestimated in both groups, they concluded.

Patients receiving azithromycin were less likely to become colonized with respiratory pathogens but were more likely to become colonized with macrolide-resistant organisms. However, no evidence suggested this was related to exacerbations or pneumonia. There were no adverse cardiac effects from azithromycin, although researchers noted that patients were excluded if they had risk factors for prolongation of the QTc interval.

The researchers concluded, “Given the deleterious effects of acute exacerbations of COPD with respect to the risk of death, quality of life, loss of lung function, and cost of care, adding azithromycin to the treatment regimen of patients who have had an acute exacerbation of COPD within the previous year or who require supplemental oxygen is a valuable option.”

However, patients should be screened for risk of QTc prolongation, hearing should be monitored, and it should be recognized that the long-term effects of this treatment on microbial resistance are not known, they cautioned.