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Macrolide maintenance treatment for bronchiectasis

PhD ceremony:Ms J. (Josje) Altenburg
When:January 09, 2017
Start:12:45
Supervisor:prof. dr. T.S. (Tjip) van der Werf
Co-supervisor:dr. W.G. Boersma
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Macrolide maintenance treatment for bronchiectasis

Bronchiectasis, pathological widening of the small and medium sized bronchi, may result from various disorders with one common trait; a faltering airway defence system. This allows for persistent bacterial infection and an augmented airway inflammatory response. Patient’s suffering is often considerable and is characterized by a chronic, productive cough and intermittent infectious exacerbations. When non-pharmaceutical treatment options fail, bronchiectasis patients with frequent exacerbations are often treated with long term, low dose antibiotics, more specifically the macrolide antibiotic azithromycin.

This medical practice is not yet based on solid evidence to confirm the efficacy of macrolide maintenance treatment and surprisingly little is known about the potential downsides of this treatment modality. In this thesis, we provide an overview of the current knowledge on bronchiectasis, its diagnostic challenges and the available treatment options. A structured clinical workup is advocated, for which a diagnostic flow chart is offered. We investigated efficacy and safety of macrolide maintenance treatment in a randomised controlled trial, describe radiological responses to treatment and some of azithromycin’s pharmacokinetic properties. We conclude by expressing our concerns on indiscriminate use of azithromycin maintenance treatment, because of its important downsides; the induction of microbial resistance, besides other detrimental effects. Ideally, azithromycin maintenance treatment should be reserved for a ‘macrolide-responsive’ phenotype of bronchiectasis patients. In this thesis we give directions for further research in this field by proposing patient characteristics which might be predictive for a beneficial response to this treatment modality.