Macrolide antibiotics for bronchiectasis

Kelly, Carol; Chalmers, James D.; Crossingham, Iain; Relph, Nicola; Felix, Lambert; Evans, David; Milan, Stephen J; Spencer, Sally

doi:10.1002/14651858.cd012406.pub2

Cited by 68 publications

(72 citation statements)

References 65 publications

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“…Furthermore, in a very recent Cochrane review from January 2018, including adults and children with non‐CF bronchiectasis, authors concluded that long‐term macrolide therapy may reduce the frequency of exacerbations and improve quality of life. Evidence was mainly derived from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children …”

Section: The Role Of Macrolides In Non‐cf Bronchiectasismentioning

confidence: 99%

A review of non‐cystic fibrosis bronchiectasis in children with a focus on the role of long‐term treatment with macrolides

Boustany¹,

Gachelin²,

Colomban³

et al. 2019

Pediatric Pulmonology

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Bronchiectasis is a rare chronic airway disease arising from several respiratory and systemic diseases. The grade of evidence for specific treatment of childhood bronchiectasis unrelated to cystic fibrosis (CF) is low with very few randomized controlled trials. Treatment has been based mainly on evidence from studies in adults with non-cystic fibrosis bronchiectasis and patients with cystic fibrosis. Recently, longterm treatment with macrolides has been proposed. These molecules offer the advantage of anti-inflammatory and immunomodulatory properties in addition to their antibacterial properties. A total of three randomized double-blind placebo-controlled trials conducted in adults showed that macrolides taken for 6-12 months led to a significant reduction in exacerbation rates. Only one long-term, randomized doubleblind placebo-controlled trial was conducted in the pediatric population. It showed that azithromycin administered weekly for up to 24 months reduced pulmonary exacerbations. Further randomized controlled studies are needed to determine the optimal dose and duration of treatment with macrolides. The clinical profile of children who would benefit from this treatment also needs to be determined. K E Y W O R D S macrolides, non-cystic-fibrosis bronchiectasis, pulmonary exacerbations

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Section: The Role Of Macrolides In Non‐cf Bronchiectasismentioning

confidence: 99%

A review of non‐cystic fibrosis bronchiectasis in children with a focus on the role of long‐term treatment with macrolides

Boustany¹,

Gachelin²,

Colomban³

et al. 2019

Pediatric Pulmonology

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“…Macrolides have important adverse effects including direct side effects, population risk of antimicrobial resistance, induction of resistance in NTM, cardiovascular effects and drug-drug interactions. 8 The results of safety evaluation of the 3 trials included in our meta-analysis are extensively reported in the primary publications and subsequent meta-analyses and so were not the focus of this manuscript. This said, the trend to worse QoL in younger patients with non-frequent exacerbations (Fig 2), may very well be a reflection of more side effects in this particular subgroup, which would be consistent with the clinical experience of the authors.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

“…7 Macrolide antibiotics are among the most widely used chronic treatments to prevent exacerbations in bronchiectasis. 8,9 They are particularly attractive because there is evidence they target each of the key components of bronchiectasis pathophysiology. In addition to reducing bacterial burden, they have well established immunomodulatory effects which include suppression of neutrophil mediated lung damage, and they also enhance cilia function to promote mucociliary clearance.…”

Section: Introductionmentioning

confidence: 99%

Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis

Chalmers

Boersma

Lonergan

et al. 2019

The Lancet Respiratory Medicine

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Evidence before this study: Data sources and searches © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ Two investigators searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials andWeb of Science using the search strategy described in the online supplement. Searches were conducted from 2000 to 30 th September 2018. No language restrictions were applied. Searches were supplemented with review of reference lists and by reviewing previous meta-analyses and guidelines. Clearly ineligible studies were excluded based on abstract review alone.We identified 266 references and after exclusion of non-relevant studies we identified 3 randomized controlled trials comparing long term treatment with macrolide antibiotics (>3 months duration) compared with placebo where the primary outcome was the reduction of exacerbations. We identified several existing aggregate meta-analyses that suggested that macrolides reduce the frequency of exacerbations of bronchiectasis. Neither the individual trials nor the existing meta-analyses reported on the effectiveness of macrolides in different subpopulations. Identifying which patients benefit from macrolides was identified as a key research priority in bronchiectasis. The current European Respiratory Society guidelines suggest consideration of macrolides for patients without Pseudomonas aeruginosa infection with a history of at least 3 exacerbations in the previous year. Added value of this study:We report the first individual patient data meta-analysis of long term macrolide therapy in bronchiectasis. Our data from 341 patients enrolled in randomized clinical trials in the Netherlands, NewZealand and Australia suggests that macrolide treatment compared to placebo for 6-12 months results in a 50% reduction in the frequency of exacerbations. Additional benefits included prolongation of the time to first exacerbation and statistically significant improvements in quality of life measured by the St Georges Respiratory Questionnaire. Lung function was not significantly improved. Analyses in prespecified subgroups including age, sex, disease severity and baseline microbiology suggested that macrolides effectively reduced exacerbations across all subgroups of patients. Importantly, macrolides had a significant and clinically meaningful impact in patients where macrolide are not currently considered as first line treatment, including patients with P. aeruginosa infection and patients with less than 3 exacerbations per year. Implications of all the available evidence:Our data suggests that macrolide therapy is highly effective in reducing the frequency of exacerbations in bronchiectasis. Given the strong evidence that exacerbations contribute to long term morbidity and mortality in bronchiectasis macrolides should be considered in patients with frequent or severe exacerbations. Current bronchiectasis guidelines recommend inhaled antibiotics as first line treatment for patients with P. aeruginosa...

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“…In a carefully observed case series in Respirology , Martin et al describe the clinicopathological features of patients with idiopathic chronic productive cough and report a favourable response to low‐dose, long‐term azithromycin, as well as some indicators of response. In doing so, they place this syndrome within the larger context of the macrolide‐responsive neutrophilic bronchitis that we recognize in bronchiectasis, chronic obstructive pulmonary disease (COPD), bronchiolitis and some forms of asthma …”

mentioning

confidence: 99%