New Antibiotic Formulations

A pitfall in the treatment of chronic lung infection in cystic fibrosis and bronchiectasis is the inability of systemic antibiotics to penetrate into the affected areas. There is currently one US Food and Drug Administration approved antibiotic formulation in cystic fibrosis, tobramycin solution for inhalation; inhaled colistin also has been used in the above diseases. Nebulization requires significant time, and intolerance, although uncommon, occurs in some patients.

However, recent research led to the development of antibiotic formulations for inhalation in both cystic fibrosis and bronchiectasis. These formulations are in different stages of clinical trials in both diseases and, if found effective, will be available for patient use. Most of these formulations consist of known antibiotics with improved efficient delivery or improved half-life, requiring fewer daily treatments.

Dry powder inhalation can lead to decreased time of administration. This method is used by tobramycin inhalation powder, which is currently in phase 3 trials (Geller et al. Pediatr Pulmonol 2007;42(4):307) and by inhaled ciprofloxacin, which is in phase 2 trials. An efficient nebulizer device has been used for aztreonam lysinate for inhalation and has successfully completed two phase 3 trials in cystic fibrosis and a phase 2 trial in bronchiectasis (Retsch-Bogart GZ et al. Chest 2009; 135(5):1223; and McCoy KS et al. Am J Respir Crit Care Med 2008;178(9):921). It is also used for nebulized levofloxacin in phase 2 trials. Another approach uses liposomes to deliver medication deep into the lungs, releasing it in a controlled fashion, leading to once daily administration. It has been used by liposomal amikacin in a phase 2 trial. These medications could lead to a dramatically different paradigm of care for patients with bronchiectasis and cystic fibrosis, resulting in better control of chronic infection, fewer exacerbations, less lung function decline, and improved compliance.

Denis Hadjiliadis, MD, MHS, FCCP
Steering Committee Member

Note: Dr. Hadjiliadis has participated, or is currently participating, as a local principal investigator in multicenter clinical trials involving aztreonam lysine for inhalation (AZLI; Gilead Pharmaceuticals) and inhaled ciprofloxacin (Bayer Pharmaceuticals).