Effect of cycled, inhaled tobramycin on the sputum microbiome in cystic fibrosis

Lung disease in the genetic disease cystic fibrosis (CF) is characterized by chronic, polymicrobial respiratory infections. Antibiotics are a cornerstone of CF lung disease treatment, however, the microbial determinants of response to antibiotics remain poorly understood. The microbiota in CF respiratory specimens are known to be relatively stable over time, even during antibiotic therapy, but less is known about how the metagenome (the predicted functional capacity of the microbiota) changes with antibiotic therapy. The commonly-used antibiotic inhaled tobramycin is known to reduce sputum densities of Pseudomonas aeruginosa and to improve lung disease measures on average in treatment-naïve patients. However, studies have failed to demonstrate a consistent relationship between changes in sputum P. aeruginosa densities and clinical outcomes. We collected CF sputum from 30 individuals with CF before, weekly during and after a standard one-month course of tobramycin, with concomitant lung function measurements and symptom scores collected from all participants. The aim of this study is compare the sputum microbiota and metagenome to clinical outcomes to identify microbial features associated with differential response to tobramycin therapy.