Pulmonary biofilm-based chronic infections and inhaled treatment strategies

Certain pulmonary diseases, such as cystic fibrosis (CF), non-CF bronchiectasis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia, are usually accompanied by respiratory tract infections due to the physiological alteration of the lung immunological defenses. Recurrent infections may lead to chronic infection through the formation of biofilms. Chronic biofilm-based infections are challenging to treat using antimicrobial agents. Therefore, effective ways to eradicate biofilms and thus relieve respiratory tract infection require the development of efficacious agents for biofilm destruction, the design of delivery carriers with biofilm-targeting and/or penetrating abilities for these agents, and the direct delivery of them into the lung. This review provides an in-depth description of biofilm-based infections caused by pulmonary diseases and focuses on current existing agents that are administered by inhalation into the lung to treat biofilm, which include i) inhalable antimicrobial agents and their combinations, ii) non-antimicrobial adjuvants such as matrix-targeting enzymes, mannitol, glutathione, cyclosporin A, and iii) liposomal formulations of anti-biofilm agents. Finally, novel agents that have shown promise against pulmonary biofilms as well as traditional and new devices for pulmonary delivery of anti-biofilm agents into the lung are also discussed.