Macrolide maintenance treatment for bronchiectasis

Abstract

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. Patients’ suffering is often considerable and is characterized by a chronic, productive cough and intermittent infectious exacerbations. In case of failure of non-pharmaceutical treatment options, bronchiectasis patients with frequent exacerbations have frequently been treated with long term, low dose antibiotic treatment, more specifically, the macrolide antibiotic azithromycin. This medical practice has not been based on solid evidence to confirm the efficacy of macrolide maintenance treatment and surprisingly little was 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 investigate 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 and in this thesis we give directions for further research in this area by proposing patient characteristics which might be predictive for a beneficial response to this treatment modality