PURPOSE: To evaluate the microbiological effect of treatment with Aztreonam for Inhalation Solution (AZLI), and corresponding change in respiratory symptoms, in patients with non-cystic fibrosis bronchiectasis and gram-negative bacteria in the airways.
METHODS: Adults with symptomatic bronchiectasis were recruited from 21 sites in the US to participate in this open-label study. Total study period was 70 days with 6 study visits every 14± 3 days. Participants were stable at enrollment, with positive sputum culture for a gram-negative pathogen. Enrolled patients took AZLI 75 mg three times daily (TID) for 28 days. Sputum samples were collected for quantitative cultures and patients completed the Quality of Life Questionnaire-Bronchiectasis (QOL-B) and spirometry at all visits.
RESULTS: Of 131 adults screened, 89 were enrolled and 82 completed the study treatment period. The most common gram-negative pathogens isolated from enrolled and treated patients were Pseudomonas aeruginosa (PA) and Achromobacter, present in 73 (82%) and 11 (12.4%) patients respectively. Nontuberculous mycobacteria (NTM) were present in 20 (22.5%) patients at screening and/or baseline. Mean CFU density at screening was 6.08 log10 CFUs/g sputum for PA, and 5.6 log10 CFUs/g sputum for Achromobacter species. Mean CFU change in sputum from baseline after AZLI treatment was -2.81 log10 CFUs (>99% reduction) for PA, and -1.93 log10 CFUs (98% reduction) for Achromobacter. Reduction in respiratory symptoms as quantified by change in the QOL-B Respiratory Symptoms score was statistically and clinically significant for PA (p< 0.001) and non-PA (p=0.004) infected subgroups, as well as for NTM-coinfected patients (p< 0.001).
CONCLUSION: Treatment with AZLI TID for 28 days resulted in significant reduction of PA and non-PA gram-negative sputum density, and statistically and clinically significant improvement in respiratory symptoms for PA-infected, non-PA infected, and NTM-coinfected patient subgroups.
CLINICAL IMPLICATIONS: AZLI is a promising new therapy for patients with bronchiectasis and gram-negative bacteria in the airways. Further placebo-controlled studies of the safety and efficacy of AZLI in this population are warranted.
DISCLOSURE: Alan Barker, Employee I am an employee of Gilead Sciences, Inc.; No Product/Research Disclosure Information