Chest
Volume 153, Issue 5, May 2018, Pages 1125-1133
Journal home page for Chest

Original Research: COPD
Clinical and Safety Outcomes of Long-Term Azithromycin Therapy in Severe COPD Beyond the First Year of Treatment

https://doi.org/10.1016/j.chest.2018.01.044Get rights and content

Background

Exacerbations of COPD (ECOPD) are a major cause of mortality and morbidity. Continuous cyclic azithromycin (CC-A) reduces the exacerbation rate, but it is unknown whether it remains effective and safe beyond the first year.

Methods

This study was a retrospective analysis of patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) with ≥ 4 moderate to severe ECOPD who received CC-A (500 mg three times per week) as add-on therapy. Patients treated over 24 months were considered long-term continuous cyclic azithromycin (LT-CC-A) users, and ECOPD, hospitalizations, and length of hospital stays during the first, second, and third years were compared with the previous 12 months. Microbiologic monitoring, assessment of macrolide resistance, and analysis of side effects were maintained throughout the study period.

Results

A total of 109 patients with severe COPD treated with CC-A (39 for ≥ 24 months) comprised the LT-CC-A group (35.8%). This group presented average reductions in ECOPD from baseline of 56.2% at 12 months, 70% at 24 months, and 41% at 36 months, paralleled by respective reductions in hospitalizations of 62.6%, 75.8%, and 39.8%. ECOPD due to common microorganisms fell by 12.5% and 17.3% at 12 and 24 months of LT-CC-A, respectively, with a 50% increase in macrolide resistance. Pseudomonas aeruginosa ECOPD rose by 7.2% and 13.1% at these two time points. CC-A therapy was well tolerated with few side effects: digestive disorders in the short term (7.1%) and hearing loss in the long term (5.1%).

Conclusions

LT-CC-A therapy over a 24- to 36-month period in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) achieved sustained reductions in ECOPD and hospitalizations of > 50% with few adverse events, although macrolide resistance increased.

Section snippets

Subjects

A cohort of 505 patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) was routinely controlled and treated at the Respiratory Day Care Unit of Sabadell Hospital between January 2007 and December 2013. Patients treated with continuous cyclic azithromycin (CC-A) for repeated ECOPD (≥ 4 in the previous year) were recruited. The group of patients receiving this treatment for at least 24 months were considered LT-CC-A users and constituted the main target

Results

A total of 109 patients with severe COPD and ≥ 4 ECOPD in the previous year from the cohort of 505 patients controlled at the Respiratory Day Care Unit were eligible for CC-A therapy and agreed to participate in the study. The ST-CC-A group comprised 70 of the 109 participants (64.2%). The median (IQR) duration of azithromycin therapy in this group was 12 (10) months. Thirty-nine patients (35.8%) were treated for ≥ 24 months and constituted the LT-CC-A group, whose baseline variables are shown

Discussion

To our knowledge, this study is the first to examine the effectiveness and safety of LT-CC-A therapy over a 24-month period in patients with severe COPD with a history of frequent exacerbations. Regarding its effectiveness, CC-A therapy achieved a significant reduction in the number of ECOPD, an effect that endured beyond the first year of treatment and until the third year. These patients undergoing long-term treatment presented a reduction in ECOPD due to cPPMs, although they also presented a

Conclusions

This study examined the effectiveness and safety of LT-CC-A therapy over a 24-month period in patients with severe COPD who had frequent exacerbations. This therapy provided a clinical benefit in these patients, with a reduction in ECOPD that was maintained beyond the first year, throughout the second, and even during the third year of treatment, especially exacerbations due to cPPMs. However, there was a slight increase in the percentage of ECOPD due to P aeruginosa and other gram-negative

Acknowledgments

Author contributions: X. P. and C. M. are guarantors of the article; they were responsible for the design of the study, patient recruitment, treatment and follow-up, and writing of the manuscript. M. B. was responsible for patient recruitment, treatment follow-up, and data collection; O. C. performed the microbiologic tests and assessments; J. C. O. conducted the statistical analysis; and M. G. and E. M. were responsible for manuscript supervision.

Financial/nonfinancial disclosures: None

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    Drs Pomares and Montón contributed equally to this manuscript and are co-first authors.

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