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Long-term Azithromycin in Children With Bronchiectasis Unrelated to Cystic Fibrosis: Treatment Effects Over Time
Don Vicendese1, Stephanie Yerkovich2, Keith Grimwood3
1Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia; School of Engineering and Mathematical Sciences, La Trobe University, Bundoora, VIC, Australia.
Insights
Long-term azithromycin treatment for children with bronchiectasis is most effective between 17 and 62 weeks. Factors like bacterial carriage and birth status influence its benefits, requiring further study for clinical application.
Area of Science:
- Pediatric Pulmonology
- Infectious Diseases
- Clinical Pharmacology
Background:
- Long-term azithromycin is used for non-cystic fibrosis bronchiectasis to reduce exacerbations.
- Optimal treatment duration and patient subgroups benefiting most remain unclear.
Purpose of the Study:
- To determine the most effective period for azithromycin treatment in pediatric bronchiectasis.
- To identify factors that modify the effects of azithromycin in this population.
Main Methods:
- Secondary analysis of a randomized controlled trial involving 89 indigenous children.
- Semi-parametric and multivariable Poisson regression models were used to analyze efficacy and modifying factors.
Main Results:
- Azithromycin reduced exacerbations between weeks 4 and 96, with peak efficacy from weeks 17 to 62.
- Factors such as nasopharyngeal bacterial carriage, nationality (New Zealand), and higher weight-for-height z scores were associated with greater benefit.
- Children born preterm showed a lower reduction in exacerbations.
Conclusions:
- Azithromycin treatment for pediatric bronchiectasis should ideally span 17 to 62 weeks for maximum benefit.
- Observed modifying factors require validation in larger studies before clinical implementation.
Background:
Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown.
Research Questions:
(i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects?
Study Design And Methods:
A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect.
Results:
Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P < .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P < .001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P = .012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P = .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P = .012).
Interpretation:
Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice.
Clinical Trials Registration:
Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.
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