Therapeutic approaches to chronic cystic fibrosis respiratory infections with available, emerging aerosolized antibiotics

Abstract

Chronic airway infection and inflammation are key events in the clinical course of cystic fibrosis (CF). The most relevant, best investigated strain of bacteria in these circumstances is Pseudomonas aeruginosa. Since pulmonary infection with P. aeruginosa is localized in the lower conducting airways, treatment is accessible with the use of inhaled aerosolized antibiotics. Tobramycin inhalation solution was the first antibiotic to be developed and approved (in 1998) for use as an aerosolized antibiotic in patients with CF. The only other aerosolized antibiotic indicated for this use is aztreonam lysine solution for inhalation, which has been approved by both European and US authorities. In prospective, randomized, controlled trails, both agents exhibited a very acceptable safety profile, along with an increase in forced expiratory volume in 1 second and other clinically relevant endpoints. New developments focus on such components as reducing the treatment burden by using dry power inhalers, decreasing inhalation frequency to once daily, penetrating P. aeruginosa biofilms, and combining two antibiotics in one solution for inhalation. However, the ideal aerosolized antibiotic regimen for the treatment of chronic P. aeruginosa infection has yet not been selected.