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


Frost, Freddy J ORCID: 0000-0002-3902-6502, Nazareth, Dilip S ORCID: 0000-0002-6114-0467, Charman, Susan C, Winstanley, Craig ORCID: 0000-0002-2662-8053 and Walshaw, Martin J (2019) Ivacaftor Is Associated with Reduced Lung Infection by Key Cystic Fibrosis Pathogens A Cohort Study Using National Registry Data. ANNALS OF THE AMERICAN THORACIC SOCIETY, 16 (11). pp. 1375-1382.

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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.

Item Type: Article
Uncontrolled Keywords: cystic fibrosis, ivacaftor, Pseudomonas aeruginosa
Depositing User: Symplectic Admin
Date Deposited: 09 Jan 2020 08:43
Last Modified: 19 Jan 2023 00:10
DOI: 10.1513/AnnalsATS.201902-122OC
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3069887
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