Ivacaftor Is Associated with Reduced Lung Infection by Key Cystic Fibrosis Pathogens: A Cohort Study Using National Registry Data.

Abstract

RATIONALE\nIvacaftor can greatly improve clinical outcomes in people with cystic fibrosis (CF) and has been shown to have in-vitro antibacterial properties, yet the long-term microbiological outcomes of treatment are unknown.\n\n\nOBJECTIVES\nTo investigate changes in respiratory microbiology associated with long-term ivacaftor use.\n\n\nMETHODS\nRetrospective cohort study utilising data from the United Kingdom CF Registry 2011-2016. Primary outcome was the annual prevalence ratios for key CF pathogens between ivacaftor users and their contemporaneous comparators. Multivariate log-binomial regression models were designed to adjust for confounders. Changes in Pseudomonas aeruginosa status were compared between groups using non-parametric maximum likelihood estimate for the purposes of Kaplan-Meier approximation.\n\n\nRESULTS\nIvacaftor use was associated with early and sustained reduction in P. aeruginosa rates (2016 Adjusted Prevalence Ratio [95% CI] 0.68 [0.58, 0.79], p<0.001) via a combination of increased clearance in those with infection (Ivacaftor: 33/87 [37.9%] vs. Non ivacaftor: 432/1872 [22.8%], p<0.001) and reduced acquisition in those without infection (33/134 [24.6%] vs. 1157/2382 [48.6%], p=0.01). The improved prevalence of P. aeruginosa infection was independent of reduced sampling in the ivacaftor cohort. Ivacaftor was also associated with reduced prevalence of Staphylococcus aureus and Aspergillus spp. but not Burkholderia cepacia complex. Conclusion In this study, long-term ivacaftor use was associated with reduced infection with important CF pathogens including P. aeruginosa. These findings have implications for antibiotic stewardship and the need for on-going chronic antimicrobial therapy in this cohort.