Long-term azithromycin use in patients with chronic obstructive pulmonary disease and tracheostomy

Abstract

Patients with Chronic Obstructive Pulmonary Disease (COPD) and tracheostomy are at high risk for exacerbations and hospitalizations. Macrolide treatment has shown to reduce exacerbations in moderate-to-severe COPD. To evaluate the safety and the efficacy of long-term azithromycin use in outpatients with severe COPD and tracheostomy. A multicenter, randomized, uncontrolled, pilot trial evaluating the safety and the efficacy of azithromycin 500 mg three day-a-week for 6 months (AZI) vs. standard of care (SC) in severe COPD outpatients with tracheostomy. Patients were monitored for six months of treatment plus six months of follow up. The primary outcome was the reduction in the number of exacerbations and hospitalizations. A total of 22 patients was randomized (11 to SC and 11 to AZI). Patients in AZI had a significant lower cumulative number of exacerbations after the first 3 months of treatment when compared to patients in SC (p = 0.001), as well as hospitalizations (p = 0.02). Kaplan-Meier survival curves for time to first exacerbation showed a significant reduction in AZI of the rates of first exacerbation when compared to SC (log rank test = 12.14, p < 0.001), as well as to first hospitalization (log-rank = 4.09, p = 0.04). Azithromycin significantly improved the quality of life in comparison to SC. No serious adverse events in the AZI group were reported. Long-term azithromycin treatment seems to be safe and effective in severe COPD outpatients with tracheostomy in reducing exacerbations, hospitalizations, as well as in improving quality of life.

Long-term macrolide treatment for chronic respiratory disease

“…the use of antibiotics prophylactically) might have a significant additional benefit in terms of exacerbation reduction [72]. A number of studies have evaluated whether long-term macrolide treatment decreases the risk of AECOPD, with conflicting results [73][74][75][76][77][78][79]. More recently, in a prospective, parallel-group study, 1142 patients with COPD at increased risk of exacerbation were randomly assigned in a 1:1 ratio to receive azithromycin (n5570) at a dose of 250 mg daily or placebo (n5572) for 1 year in addition to their usual care [80].…”

Azithromycin Attenuates Pulmonary Inflammation and Emphysema in Smoking-Induced COPD Model in Rats

“…[14][15][16] Long-term azithromycin (Azm) therapy was associated with significant reductions in the rate of exacerbations compared with placebo. 17,18 However, the mechanism of the anti-inflammatory/immunomodulatory actions of macrolides remains unclear. There are few reports on the role of Azm in the treatment of CS-induced COPD in rats.…”

Azithromycin for Prevention of Exacerbations of COPD

“…Two of the studies showed no effect, but one of these used a retrospective design 29 and the other was conducted for only 3 months, and very few acute exacerbations of COPD occurred in either group. 26 Five studies have reported that macrolides decrease acute exacerbations of COPD, but one of these was not a blinded study, 27 two did not include concurrent controls, 31,32 and one involved only 35 patients. 30 Seemungal and colleagues performed a well-designed, randomized, 1-year trial of erythromycin, at a dose of 250 mg twice daily, in 109 patients (a study that was stopped before the target enrollment was met).…”

“…[26][27][28][29][30][31][32] We found that more participants receiving azithromycin met the criteria for development of a hearing decrement than did those receiving placebo, but the improvements in hearing that occurred on repeat testing, regardless of whether the study drug was discontinued, suggest that our criteria were too stringent and that the incidence of hearing decrements was overestimated in both groups.…”

“…25 Seven small studies that tested whether macrolides decrease the frequency of acute exacerbations of COPD reported conflicting results. [26][27][28][29][30][31][32] Accordingly, we conducted a large, randomized trial to test the hypothesis that azithromycin decreases the frequency of acute exacerbations of COPD when added to the usual care of these patients.…”