Cystic Fibrosis Microbiome-directed Antibiotic Therapy Trial in Exacerbations Results Stratified (CFMATTERS): Results of a multi-centre randomised controlled trial.

IF 21 1区 医学 Q1 RESPIRATORY SYSTEM
Barry J Plant, Gisli G Einarsson, Kevin F Deasy, Darren Dahly, Pradeep K Singh, Peter J Barry, Christopher H Goss, Isabelle Fajac, Tamara Vagg, Isabelle Durieu, Evelyn Flanagan, Grace O'Callaghan, Clémence Martin, Pierre-Régis Burgel, Charles S Haworth, R Andres Floto, Damian G Downey, Lieven J Dupont, Andrew M Jones, J Stuart Elborn, Joseph A Eustace, Marcus A Mall, Michael M Tunney
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引用次数: 0

Abstract

Background: This study explores the effectiveness and safety of microbiome-directed-antimicrobial-therapy versus usual-antimicrobial-therapy in adult cystic fibrosis pulmonary exacerbations.

Methods: A multi-centre two-arm parallel randomised control trial conducted across Europe/North-America enrolled 223 participants (January 2015 - August 2017). All participants were chronically colonised with Pseudomonas aeruginosa and were randomised 1:1 into two study-arms. The "usual-therapy group" received 2-weeks of IV ceftazidime 3g thrice-daily (for allergies: aztreonam 2g thrice-daily) and tobramycin 5-10mg·kg-1 once-daily. The "microbiome-directed group" received the same usual-therapy plus an additional antibiotic with greatest presumed activity against the 2nd, 3rd and 4th most abundant genera present in the sputum microbiome, selected by a Consensus Expert Treatment Panel. The primary outcome was change in percentage of predicted FEV1 (ppFEV1) at 14 days post initiation of antibiotics. Secondary outcomes examined ppFEV1 at 7 days, 28 days, and 3 months; time-to-next exacerbation; symptom burden at 7 days; Health Related Quality of Life (HRQoL) at 28 days; and number of exacerbations and IV antibiotic days at 12 months.

Results: 149 participants had an eligible exacerbation (usual-therapy n=83, microbiome-directed therapy n=66). There was no difference between the groups for ppFEV1 at day 14 (-1.1%, 95%CI -3.9 to 1.7; p=0.46), or ppFEV1 measured at other time-points, or for time-to-next exacerbation (microbiome-directed versus usual-therapy Hazard Ratio 0.91 [95%CI 0.60 to 1.38; p=0.66]). The microbiome-directed group trended to have more IV days (median 42 versus 28; p=0.08) and more subsequent exacerbations (median 3 versus 2; p=0.044) the following year. There were no appreciable differences in symptom burden; however, HRQoL sub-scores were consistently worse in the microbiome-directed group (-4.3 points versus usual therapy (95%CI -8.3 to -0.3, p=0.033).

Conclusion: The addition of a third antibiotic based on sputum microbiome sequencing analysis did not result in improved clinical outcomes.

囊性纤维化微生物组导向的抗生素治疗加重试验结果分层(CFMATTERS):一项多中心随机对照试验的结果。
背景:本研究探讨了微生物组定向抗菌治疗与常规抗菌治疗在成人囊性纤维化肺加重中的有效性和安全性。方法:2015年1月至2017年8月,在欧洲/北美进行了一项多中心、双臂平行随机对照试验,共有223名参与者。所有参与者慢性感染铜绿假单胞菌,并按1:1随机分为两个研究组。常规治疗组给予头孢他啶3g静脉滴注,每日3次(过敏组:氨曲南2g每日3次),妥布霉素5-10mg·kg-1,每日1次,为期2周。“微生物组导向组”接受相同的常规治疗,加上一种额外的抗生素,该抗生素对痰中微生物组中第二、第三和第四丰富的属具有最大的活性,由共识专家治疗小组选择。主要结局是在开始使用抗生素后14天预测FEV1百分比(ppFEV1)的变化。次要结局是在7天、28天和3个月时检测ppFEV1;time-to-next恶化;7天症状负担;28天健康相关生活质量(HRQoL);以及12个月时病情加重次数和静脉注射抗生素天数。结果:149名参与者有符合条件的恶化(常规治疗n=83,微生物组导向治疗n=66)。第14天,两组间ppFEV1无差异(-1.1%,95%CI -3.9 ~ 1.7;p=0.46),或其他时间点测量的ppFEV1,或下一次加重的时间(微生物组导向与常规治疗的风险比0.91 [95%CI 0.60至1.38;p = 0.66)。微生物组组的IV天更长(中位42天和28天;P =0.08)和更多的后续恶化(中位3 vs 2;P =0.044)。两组在症状负担上无明显差异;然而,微生物组组的HRQoL亚评分一直较差(-4.3分与常规治疗相比(95%CI -8.3至-0.3,p=0.033)。结论:基于痰微生物组测序分析添加第三种抗生素并没有改善临床结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
European Respiratory Journal
European Respiratory Journal 医学-呼吸系统
CiteScore
27.50
自引率
3.30%
发文量
345
审稿时长
2-4 weeks
期刊介绍: The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.
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