Effect of maintenance macrolide de-escalation during the Australian summer on exacerbations of obstructive airway diseases: a randomised, double-blind, placebo-controlled trial.

Authors

Dennis Thomas, Vanessa McDonald, Peter Ab Wark, Shyamala Pradeepan, Scott Twaddell, Andrew Gillman, Mark Hew, Eve Denton, Joy Lee, Jimmy Chien, Madeleine Hinwood, Erin S Harvey, Gijo Thomas, Amber Smith, David Arnold, Peter G Gibson

Published in

Thorax. Jul 28, 2026. Epub Jul 28, 2026.

Abstract

The optimal duration of maintenance macrolide antibiotic therapy in obstructive airway disease (OAD) remains unclear. This study evaluated the impact of de-escalating maintenance macrolide therapy during the Australian summer on OAD exacerbations.
This double-blind, placebo-controlled, non-inferiority trial recruited 82 participants (mean age: 67.33±13.13; 55% female) undergoing maintenance macrolide therapy for the management of asthma, chronic obstructive pulmonary disease or bronchiectasis. They were randomised to continue (continuation arm) or de-escalate macrolide therapy (de-escalation arm) at the start of the summer (December-February). Follow-up interviews were conducted at 3, 6 and 9 months. The primary outcome was acute exacerbations during the summer. Secondary outcomes included symptom control scores and time to first exacerbation. The non-inferiority margin was 20%.
The acute exacerbation rates were 33.3% (14/42) for the continuation arm and 50% (19/38) for the de-escalation arm during the summer season. The primary analysis did not demonstrate non-inferiority (risk difference 16.2%; 95% CI -4.9% to 37.2%, with the upper bound exceeding the 20% non-inferiority margin). Symptom control was maintained and did not differ between arms. The time to first exacerbation was longer in the continuation arm (median 206 vs 90 days; HR 1.98, 95% CI 1.15 to 3.42; p=0.012).
Macrolide de-escalation was not found to be non-inferior to continued treatment in individuals with OAD. While some patients may be able to discontinue long-term macrolide therapy during the summer, there remains a risk of exacerbation recurrence.
ACTRN12620001263987.

PMID:
42521618
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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