Liverpool Adult Cystic Fibrosis Centre, Liverpool Heart and Chest Hospital NHS, Foundation Trust, Liverpool, United Kingdom.
Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom; and.
Ann Am Thorac Soc. 2019 Nov;16(11):1375-1382. doi: 10.1513/AnnalsATS.201902-122OC.
Ivacaftor can greatly improve clinical outcomes in people with cystic fibrosis (CF) and has been shown to have antibacterial properties, yet the long-term microbiological outcomes of treatment are unknown. To investigate changes in respiratory microbiology associated with long-term ivacaftor use. 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 status were compared between groups using nonparametric maximum likelihood estimate for the purposes of Kaplan-Meier approximation. Ivacaftor use was associated with early and sustained reduction in rates (2016 adjusted prevalence ratio, 0.68; 95% confidence interval, 0.58-0.79; < 0.001) via a combination of increased clearance in those with infection (ivacaftor: 33/87 [37.9%] vs. nonivacaftor: 432/1,872 [22.8%]; < 0.001) and reduced acquisition in those without infection (49/134 [36.6%] vs. 1,157/2,382 [48.6%]; = 0.01). The improved prevalence of infection was independent of reduced sampling in the ivacaftor cohort. Ivacaftor was also associated with reduced prevalence of and spp. but not complex. In this study, long-term ivacaftor use was associated with reduced infection with important CF pathogens including . These findings have implications for antibiotic stewardship and the need for ongoing chronic antimicrobial therapy in this cohort.
依伐卡托特可显著改善囊性纤维化（CF）患者的临床结局，并具有抗菌特性，但长期治疗的微生物学结局尚不清楚。本研究旨在调查长期使用依伐卡托特与呼吸微生物组学变化之间的关系。这是一项回顾性队列研究，使用了 2011-2016 年英国 CF 登记处的数据。主要结局是依伐卡托特使用者与同期对照者之间关键 CF 病原体的年度流行率比值。设计了多变量对数二项式回归模型，以调整混杂因素。使用非参数最大似然估计来比较两组之间的 状态变化，以便进行 Kaplan-Meier 逼近。通过感染清除增加（依伐卡托特：33/87 [37.9%] vs. 非依伐卡托特：432/1,872 [22.8%]； < 0.001）和减少未感染人群的获得（依伐卡托特：49/134 [36.6%] vs. 1,157/2,382 [48.6%]； = 0.01），依伐卡托特的使用与感染率的早期和持续降低相关。在依伐卡托特组中，采样减少对改善感染的流行率没有影响。依伐卡托特还与 减少有关，但与 减少无关。在这项研究中，长期使用依伐卡托特与包括 在内的重要 CF 病原体感染率降低有关。这些发现对该队列中抗生素管理和持续慢性抗菌治疗的必要性具有影响。
