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
{"title":"Cystic Fibrosis Microbiome-directed Antibiotic Therapy Trial in Exacerbations Results Stratified (CFMATTERS): Results of a multi-centre randomised controlled trial.","authors":"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","doi":"10.1183/13993003.02443-2024","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study explores the effectiveness and safety of microbiome-directed-antimicrobial-therapy <i>versus</i> usual-antimicrobial-therapy in adult cystic fibrosis pulmonary exacerbations.</p><p><strong>Methods: </strong>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 <i>Pseudomonas aeruginosa</i> 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<sup>-1</sup> 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 FEV<sub>1</sub> (ppFEV<sub>1</sub>) at 14 days post initiation of antibiotics. Secondary outcomes examined ppFEV<sub>1</sub> 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.</p><p><strong>Results: </strong>149 participants had an eligible exacerbation (usual-therapy n=83, microbiome-directed therapy n=66). There was no difference between the groups for ppFEV<sub>1</sub> at day 14 (-1.1%, 95%CI -3.9 to 1.7; p=0.46), or ppFEV<sub>1</sub> measured at other time-points, or for time-to-next exacerbation (microbiome-directed <i>versus</i> 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 <i>versus</i> 28; p=0.08) and more subsequent exacerbations (median 3 <i>versus</i> 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 <i>versus</i> usual therapy (95%CI -8.3 to -0.3, p=0.033).</p><p><strong>Conclusion: </strong>The addition of a third antibiotic based on sputum microbiome sequencing analysis did not result in improved clinical outcomes.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Respiratory Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/13993003.02443-2024","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
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.
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.