Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?

Abstract

The key message from our review is that this class of agents may prove to be a useful therapeutic option for a range of respiratory diseases, but that further trials and mechanistic studies are required to clarify their role.

Emerging anti-inflammatory strategies for COPD

“…A possible explanation for the apparent limited efficacy of antiinflammatory therapy in COPD is that by the time COPD has become clinically apparent, the disease is already moderately advanced, with irreversible parenchymal damage, thus limiting the benefits of anti-inflammatory treatments alone, particularly with respect to lung function [113]. Therefore, the reason for the discrepancy between the animal data and human trials probably relates, in a large part, to the inability to produce severe COPD in laboratory animals.…”

“…Macrolides elicit anti-inflammatory effects that may be independent of their antibiotic effects [113]. They modulate inflammatory and immune responses without affecting homeostatic immunity [114,115].…”

“…In the setting of chronic inflammation, low-dose macrolides decrease the production of proinflammatory cytokines and chemokines by epithelial and immune cells [113][114][115]. These activities are inhibitory in nature and extend to the modulation of adhesion molecules essential to the process of recruiting neutrophils at the site of inflammation [116].…”

Azithromycin Inhibits Expression of the GacA-Dependent Small RNAs RsmY and RsmZ in Pseudomonas aeruginosa

“…Although AZM does not inhibit planktonic growth of the opportunistic pathogen Pseudomonas aeruginosa at therapeutically relevant doses, the antibiotic has nevertheless been found to have beneficial effects in the treatment of chronic P. aeruginosa lung infections in cystic fibrosis patients. The observed improvement of pulmonary function may result from a combination of several mechanisms, among which the anti-inflammatory effects and the antibiofilm and antivirulence properties of AZM appear to be most important (10,16,29,30,39,51). Beneficial effects of AZM have also been seen in experimental urinary tract infections caused by P. aeruginosa (1).…”

173 A Randomised Controlled Trial of Azithromycin Therapy in Bronchiolitis Obliterans Syndrome (BOS) Post Lung Transplantation

“…These include gastrointestinal effects, loss of hearing 36 and the development of macrolide resistant organisms. 34 It is also suggested that azithromycin could predispose patients to the development of non-TB mycobacterial infection. 37 Debate has also been generated by a study of azithromycin use in a group of patients with preexisting heart disease.…”