Aerosol antibiotics in cystic fibrosis

Abstract

Chronic airways infection and inflammation is the greatest source of morbidity and mortality in cystic fibrosis (CF) patients. Many organisms can be found in the lower respiratory tract of CF patients, but infection with mucoid Pseudomonas aeruginosa is common, is associated with poorer outcomes, and is the main target for antimicrobial strategies in CF. Aerosol antibiotics achieve high local concentrations in the airways, reduce systemic toxicity, and have been used successfully for chronic suppressive treatment for established P. aeruginosa infections. Eradication of early P. aeruginosa airway infection has also been tried with aerosol antibiotics, though the ideal treatment strategy is still being investigated. There are several variables to consider when choosing an antibiotic formulation to develop for topical inhalation. Tobramycin solution for inhalation (TSI) is currently the only approved inhaled antibiotic in the United States. The time burden for patients to administer TSI by jet nebulizer is substantial, so efforts have focused on more efficient, faster delivery methods. Novel formulations of aerosol antibiotics are being studied for CF, including beta-lactams, fluoroquinolones and aminoglycosides. Phase-3 studies of aztreonam lysinate for inhalation delivered via a proprietary eFlow nebulizer showed improved outcomes and a short (< 3 min) delivery time. Liposome formulations are being studied as a way to penetrate mucoid biofilms and prolong the residence time of the antibiotic in the lungs. Light, porous, dry-powder formulations are also in clinical trials to reduce delivery time. These new formulations and delivery systems promise to expand our armamentarium against microbes while reducing the time burden for patients.