BACKGROUND: Culture-independent molecular techniques could potentially be used to measure microbiological efficacy in response to antibiotic treatment and improve understanding of the role of the airway microbiota in determining response in patients with chronic respiratory disease. METHODS: Using molecular methods, we analysed changes in the sputum microbiota in samples from 107 participants with bronchiectasis recruited to the iBEST-1 study, and defined community endotypes based on response to tobramycin inhalation powder (TIP) treatment. The relationship between microbiota metrics in these endotypes and clinical and inflammatory biomarkers were also determined. RESULTS: There was a significant reduction in Pseudomonas aeruginosa density, measured by quantitative polymerase chain reaction (qPCR), between Days 1 and 29 for participants in the TIP treatment (n=63; p<0.0001) but not placebo (n=20; p>0.05) group. Based on decrease in P. aeruginosa density (oprL copies·mL(-1)) over 28 days, two clusters of participants receiving TIP were observed and stratified as either responders (
