A NEW international trial has investigated the safety and efficacy of tailoring antibiotic treatment for cystic fibrosis (CF) exacerbations based on sputum microbiome analysis.
Conducted across Europe and North America, the study enrolled 223 patients chronically colonised with Pseudomonas aeruginosa between January 2015–August 2017. The aim was to assess whether microbiome-directed antimicrobial therapy could outperform standard care in adults with CF experiencing pulmonary exacerbations. Participants were randomised 1:1 to receive either usual intravenous antibiotics (ceftazidime or aztreonam with tobramycin) or the same regimen plus a third antibiotic selected to target the 2nd, 3rd, and 4th most abundant bacterial genera in each patient’s sputum microbiome, as determined by a consensus expert panel. The primary endpoint was change in percentage predicted FEV1 (ppFEV1) at Day 14, with secondary outcomes including ppFEV1 at other time points, time to next exacerbation, symptom burden, health-related quality of life, and cumulative exacerbations and antibiotic use over 12 months.
Of 149 patients with an eligible exacerbation (usual therapy n=83, microbiome-directed n=66), no significant difference was observed in the primary outcome (mean difference: -1.1%, 95% CI: -3.9–1.7; p=0.46). Similarly, ppFEV1 at other time points and time-to-next exacerbation showed no meaningful differences. Concerningly, patients in the microbiome-directed group had a trend towards more intravenous antibiotic days (median 42 versus 28; p=0.08) and significantly more exacerbations over the following year (median 3 versus 2; p=0.044). Symptom burden was comparable between groups, but health-related quality of life scores were worse in the microbiome-guided arm (-4.3 points, 95% CI: -8.3− -0.3; p=0.033).
These results suggest that microbiome-based antibiotic selection, while mechanistically promising, does not currently improve outcomes in CF pulmonary exacerbations and may increase treatment burden. Further refinement of precision approaches is warranted before routine clinical application.
Reference
Plant BJ et al. Cystic Fibrosis Microbiome-directed Antibiotic Therapy Trial in Exacerbations Results Stratified (CFMATTERS): results of a multi-centre randomised controlled trial. Eur Respir J. 2025; DOI: 10.1183/13993003.02443-2024.
