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

Abstract

<b>Rationale:</b> Ivacaftor can greatly improve clinical outcomes in people with cystic fibrosis (CF) and has been shown to have <i>in vitro</i> antibacterial properties, yet the long-term microbiological outcomes of treatment are unknown.<b>Objectives:</b> To investigate changes in respiratory microbiology associated with long-term ivacaftor use.<b>Methods:</b> This was a retrospective cohort study using data from the UK CF Registry 2011-2016. Primary outcome was the annual prevalence ratios for key CF pathogens between ivacaftor users and their contemporaneous comparators. Multivariable log-binomial regression models were designed to adjust for confounders. Changes in <i>Pseudomonas aeruginosa</i> status were compared between groups using nonparametric maximum likelihood estimate for the purposes of Kaplan-Meier approximation.<b>Results:</b> Ivacaftor use was associated with early and sustained reduction in <i>P. aeruginosa</i> rates (2016 adjusted prevalence ratio, 0.68; 95% confidence interval, 0.58-0.79; <i>P</i> < 0.001) via a combination of increased clearance in those with infection (ivacaftor: 33/87 [37.9%] vs. nonivacaftor: 432/1,872 [22.8%]; <i>P</i> < 0.001) and reduced acquisition in those without infection (49/134 [36.6%] vs. 1,157/2,382 [48.6%]; <i>P</i> = 0.01). The improved prevalence of <i>P. aeruginosa</i> infection was independent of reduced sampling in the ivacaftor cohort. Ivacaftor was also associated with reduced prevalence of <i>Staphylococcus aureus</i> and <i>Aspergillus</i> spp. but not <i>Burkholderia cepacia</i> complex.<b>Conclusions:</b> In this study, long-term ivacaftor use was associated with reduced infection with important CF pathogens including <i>P. aeruginosa</i>. These findings have implications for antibiotic stewardship and the need for ongoing chronic antimicrobial therapy in this cohort.