Aztreonam Lysine for Inhalation Solution In Cystic Fibrosis

Aztreonam is a monobactam antibacterial with bactericidal activity against a wide range of aerobic Gram-negative bacteria, including Pseudomonas aeruginosa. Aztreonam lysine for inhalation solution (AZLI) does not contain the potentially inflammatory component arginine, which is used as a buffer in the intravenous formulation. Two phase III, randomized, placebo-controlled trials (AIR-CF1 and AIR-CF2) have been completed with AZLI in cystic fibrosis patients with pulmonary P. aeruginosa infection. In AIR-CFI, respiratory symptoms were significantly improved with AZLI compared with placebo, as assessed by the respiratory symptoms domain of the Cystic Fibrosis Questionnaire-Revised, a disease-specific, patient-reported outcome instrument. The mean treatment effect exceeded the minimal clinically important difference. In AIR-CF2, AZLI was compared with placebo following a 28-day course of tobramycin inhalation solution. AZLI was associated with a significant delay in the need for inhaled or intravenous antipseudomonal antibacterials, as determined by the presence of one of four predefined symptoms shown to be predictive of pulmonary exacerbations. An open-label extension of these trials (AIR-CF3) also demonstrated clinical efficacy with repeated courses of AZLI over 18 months and was not associated with sustained reductions in P. aeruginosa susceptibility. AZLI was also associated with improved pulmonary function and reductions in P. aeruginosa density in sputum in clinical trials. The tolerability profile of AZLI was generally similar to that of placebo in randomized controlled trials, with respiratory symptoms being the most frequently reported adverse events.