Long‐term macrolide treatment of chronic inflammatory airway diseases: risks, benefits and future developments

Abstract

Macrolide antibiotics were discovered over 50 years ago and following their use as antimicrobials it became apparent that this group of antibiotics also possessed anti-inflammatory properties. Subsequent clinical trials showed benefits of macrolides as long-term adjuncts in the treatment of a spectrum of chronic inflammatory respiratory diseases, particularly diffuse panbronchiolitis, cystic fibrosis, post-transplant bronchiolitis obliterans and more recently chronic obstructive pulmonary disease (COPD). The evidence for efficacy of macrolides in the long-term treatment of chronic asthma and bronchiectasis is less well established. The mechanism(s) of action of macrolides in the treatment of these diseases remains unexplained, but may be due to their antibacterial and/or anti-inflammatory actions, which include reductions in interleukin-8 production, neutrophil migration and/or function. Macrolides have additional potentially beneficial properties including anti-viral actions and an ability to restore corticosteroid sensitivity. The increased prescribing of macrolides for long-term treatment could result in the development of microbial resistance and adverse drug effects. New macrolides have been developed which do not possess any antimicrobial activity and hence lack the ability to produce microbial resistance, but which still retain immunomodulatory effects. Potentially novel macrolides may overcome a significant barrier to the use of this type of drug for the long-term treatment of chronic inflammatory airway diseases.

Effects of Macrolide Antibiotics on Th1 Cell and Th2 Cell Development Mediated by Langerhans Cells

“…In our previous study, we succeeded in generating LC-like dendritic cells (LDCs) from murine bone marrow cells as substitute cells for LCs, and through them developed Th1 cells or Th2 cells (15). Although it is well known that macrolide antibiotics have immunomodulatory effects in addition to their bactericidal activity (16,17), it is unclear whether they inhibit Th2 cell development mediated by LCs. In this study, therefore, we investigated the effects of macrolide antibiotics on LDCs.…”

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

“…It has generally consisted of macrolide antibiotics (azithromycin, AZ, or clarithromycin), non-steroid antiinflammatory drugs (ibuprofen or nimesulide), and, rarely, alternating courses of oral corticosteroids in low doses [8][9][10][11] . Inhaled corticosteroids cannot be considered an anti-inflammatory treatment since results of the most recent meta-analysis of their effectiveness, which included data from 13 trials, failed to show support for their use in children and adults with CF [12] .…”

Bronchiolitis in a Patient with Ulcerative Colitis Treated with Erythromycin

“…Macrolide antibiotics, including EM, now possess antiinflammatory properties, and the effects of long-term treatment with these agents on several chronic inflammatory respiratory diseases, including DPB, cystic fibrosis, posttransplant bronchiolitis obliterans and chronic obstructive pulmonary disease, have been investigated (10). Precisely how EM therapy exerts beneficial effects on bronchiolitis associated with UC is unknown; however, the actions of macrolides are generally thought to be due to immunemodifying, rather than direct antimicrobial, activities (11).…”