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

Methods

A multicentre two-arm parallel randomised control trial conducted across Europe/North-America enrolled 223 participants (January 2015 to August 2017).

该研究是一项在欧洲/北美进行的多中心两臂平行随机对照试验，共纳入了223名参与者（2015年1月至2017年8月）。

All participants were chronically colonised with Pseudomonas aeruginosa and were randomised 1:1 into two study arms.

所有参与者均长期定植铜绿假单胞菌，并按1:1的比例随机分为两个研究组。

The "usual therapy" group received 2 weeks of intravenous ceftazidime 3 g thrice daily (for allergies: aztreonam 2 g thrice daily) and tobramycin 5-10 mg·kg-1 once daily.

"常规治疗"组接受了为期2周的静脉注射头孢他啶3克，每日三次（对过敏者：每日三次注射氨曲南2克）以及托布拉霉素5-10毫克/公斤，每日一次。

The "microbiome-directed" group received the same usual therapy plus an additional antibiotic with greatest presumed activity against the second, third and fourth most abundant genera present in the sputum microbiome, selected by a consensus expert treatment panel.

“微生物组指导”组接受了相同的常规治疗，外加一种额外的抗生素，这种抗生素对痰液微生物组中第二、第三和第四大丰富的属具有最大的假定活性，由共识专家治疗小组选定。

The primary outcome was change in percentage of predicted forced expiratory volume in 1 s (ppFEV1) at 14 days post initiation of antibiotics.

主要结果是抗生素治疗开始后14天内，预计第一秒用力呼气量（ppFEV1）百分比的变化。

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 i.v. antibiotic days at 12 months.

次要结果包括在7天、28天和3个月时的ppFEV1；下一次加重的时间；7天时的症状负担；28天时的健康相关生活质量（HRQoL）；以及在12个月时的加重次数和静脉抗生素使用天数。

Results

149 participants had an eligible exacerbation (usual therapy n=83, microbiome-directed therapy n=66).

共有149名参与者发生了符合条件的加重（常规治疗组n=83，微生物组导向治疗组n=66）。

There was no difference between the groups for ppFEV1 at day 14 (-1.1%, 95% CI -3.9-1.7%; p=0.46), or ppFEV1 measured at other time points, or for time to next exacerbation (microbiome-directed versus usual therapy hazard ratio0.91, 95% CI 0.60-1.38; p=0.66).

两组在第14天的ppFEV1（-1.1%，95% 置信区间 -3.9-1.7%；p=0.46）或在其他时间点测量的ppFEV1，以及下一次加重的时间上没有差异（微生物组指导治疗与常规治疗的风险比为0.91，95% 置信区间 0.60-1.38；p=0.66）。

The microbiome-directed group trended to have more i.v. days (median 42 days versus 28 days; p=0.08) and more subsequent exacerbations (median three versus two; p=0.044) the following year.

微生物组指导组的趋势是接下来一年内有更多的静脉输液天数（中位数42天对比28天；p=0.08）和更多的随后加重（中位数三次对比两次；p=0.044）。

There were no appreciable differences in symptom burden; however, HRQoL subscores were consistently worse in the microbiome-directed group (-4.3 points versus usual therapy, 95% CI -8.3--0.3 points; p=0.033).

症状负担没有显著差异；然而，健康相关生活质量（HRQoL）子分数在微生物组指导组中持续较差（与常规治疗相比，-4.3分，95%置信区间-8.3至-0.3分；p=0.033）。

Conclusions

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

基于痰液微生物组测序分析添加的第三种抗生素并未导致临床结果的改善。