Clinical implement of Probe-Capture Metagenomics in sepsis patients: A multicentre and prospective study.

Summary

In a multicenter prospective cohort (n=184), probe-capture metagenomics outperformed blood culture for pathogen detection (51.6% vs 17.4%, p<.001), achieved 100% sensitivity and 87.1% specificity versus a composite standard, and prompted antibiotic changes in 34.8% of patients. Notably, 22.3% had a >2-point SOFA score decrease after therapy adjustment, demonstrating clinical impact beyond diagnostic yield.

Key Findings

• Detection rate was higher than blood culture (51.6% vs 17.4%, p<.001).
• Against combined blood culture + RT-PCR reference, sensitivity was 100%, specificity 87.1%, concordance 91.8%.
• Antibiotics were adjusted in 34.8% of patients, and 22.3% achieved >2-point SOFA reduction after adjustment.

Clinical Implications

Probe-capture metagenomics can be integrated early (pre-antibiotics) to increase diagnostic yield and guide antibiotic optimization, with measurable improvements in organ dysfunction (SOFA). Implementation should pair with stewardship protocols and confirmatory testing.

Limitations

• Nonrandomized design and modest sample size (n=184) may introduce selection bias
• Potential false positives/negatives inherent to capture panels; limited longer-term outcomes beyond 7 days

Future Directions

Cluster-randomized or stepped-wedge trials comparing probe-capture metagenomics-guided therapy versus standard care with 28-day mortality and cost-effectiveness endpoints; optimization of probe panels and contamination controls.