WS02.4 Short-term and long-term effects of ivacaftor treatment on sputum microbiota in people with the G551D CFTR mutation

Abstract

Objectives Treatment of people with CFTR gating mutations with ivacaftor leads to significant improvements in lung disease severity. Little is known about ivacaftor's effects on sputum microbiology, particularly early during treatment. Methods We used Illumina sequencing and quantitative PCR (qPCR) to define the microbiota in longitudinal sputa from 12 subjects with G551D mutations. Sputum was collected before (day 0) and at days 2, 7–8, and 210 of ivacaftor treatment. Sequencing was of the bacterial 16S rRNA gene V4/V5 regions. qPCR quantified all bacteria using universal bacterial primers, and individual taxa with specific primers. Diversity was defined using the Shannon Index. Results Among the 8 subjects culture-positive for P. aeruginosa , relative and absolute abundances of P. aeruginosa decreased significantly at days 7/8 (p = 0.046 for absolute abundance) and 210 (p = 0.025) compared with day 0, similar to observations from cultures. No other significant, generalized and persistent changes in abundances of specific taxa were found, including for S. aureus . Total bacterial abundance decreased significantly by day 7/8 (p = 0.007), but no significant difference was observed between day 0 and 210 (p = 0.22). There was a trend towards increased overall diversity from days 0–210 that did not reach significance. Conclusion P. aeruginosa sputum abundance decreased within days of beginning ivacaftor and for at least 210 days thereafter. There were no other uniform, persistent sputum changes in densities either of other microbial taxa or of all bacteria observed with ivacaftor treatment. The reason for the greater change in P. aeruginosa sputum density remains to be defined.