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

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-04-03 DOI:10.1002/ctm2.70297

Qin Sun, Ran Teng, Qiankun Shi, Yun Liu, Xing Cai, Bin Yang, Quan Cao, Chang Shu, Xu Mei, Weiqi Zeng, Bingxue Hu, Junyi Zhang, Haibo Qiu, Ling Liu

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引用次数: 0

Abstract

Background

Accurate pathogen identification is critical for managing sepsis. However, traditional microbiological methods are time-consuming and exhibit limited sensitivity, particularly with blood samples. Metagenomic sequencing of plasma or whole blood was highly affected by the proportion of host nucleic acid.

Methods

We developed a Probe-Capture Metagenomic assay and established a multicentre prospective cohort to assess its clinical utility. In this study, 184 blood samples from patients suspected of sepsis were sent for blood culture and Probe-Capture Metagenomic sequencing before using antibiotics. The pathogen-positive rate and auxiliary abilities in diagnosis were compared among Probe-Capture Metagenomics, blood culture and real-time PCR (RT-PCR). Antibiotic therapy adjustments were based on the identification of pathogens, and changes in the Sequential Organ Failure Assessment (SOFA) score were monitored on days 0, 3 and 7 of admission.

Results

A total of 184 sepsis patients were enrolled, with a mean age of 66 years (range 56–74). The Probe-Capture Metagenomics method, confirmed by RT-PCR, demonstrated a significantly higher pathogen detection rate than blood culture alone (51.6% vs. 17.4%, p < .001). When combining the results of blood culture and RT-PCR, Probe-Capture Metagenomics achieved a concordance rate of 91.8% (169/184), with a sensitivity of 100% and specificity of 87.1%. In terms of clinical impact, antibiotic therapy was adjusted for 64 patients (34.8%) based on the results from Probe-Capture Metagenomics, and 41 patients (22.3%) showed a > 2-point decrease in SOFA score following antibiotic adjustments.

Conclusion

Probe-Capture Metagenomics significantly enhances the ability of pathogen detection compared with traditional metagenomics. Compared to blood culture and RT-PCR in sepsis patients, it leads to improved antibiotic treatment and better patient outcomes. This study, for the first time, evaluates the clinical impact of metagenomic sequencing by integrating antibiotic adjustments and SOFA score changes, indicating that approximately one-fifth of sepsis patients benefit from this advanced diagnostic approach.

Trial registration

This study has been registered in clinical trials (clinicaltrials.gov) on 30 November 2018, and the registration number is NCT03760315.

Key points

Probe-Capture Metagenome had a significantly higher positive rate than blood culture (51.6% vs. 17.4%, p < .001).
Combining blood culture and RT-PCR results, Probe-Capture Metagenome achieved a consistency rate of 91.8%.
Antibiotics were adjusted in 34.8% of patients based on Probe-Capture Metagenome results, and 22.3% of patients experienced a more than 2-point decrease in SOFA score.

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探针捕获宏基因组学在脓毒症患者中的临床应用：一项多中心前瞻性研究

背景准确的病原体鉴定对脓毒症的治疗至关重要。然而，传统的微生物学方法耗时且灵敏度有限，特别是对血液样本。血浆或全血宏基因组测序受宿主核酸比例影响较大。方法我们开发了一种探针捕获宏基因组分析方法，并建立了一个多中心前瞻性队列来评估其临床应用。在本研究中，184例疑似脓毒症患者的血液样本在使用抗生素前进行了血液培养和探针捕获宏基因组测序。比较探针捕获宏基因组学、血培养和实时荧光定量PCR （RT-PCR）对病原菌的阳性率和辅助诊断能力。根据病原体的鉴定调整抗生素治疗，并在入院第0,3和7天监测序贯器官衰竭评估（SOFA）评分的变化。结果共纳入184例败血症患者，平均年龄66岁（56-74岁）。经RT-PCR证实，探针捕获宏基因组法的病原体检出率明显高于单纯血培养法(51.6% vs. 17.4%, p <；措施)。结合血培养结果和RT-PCR结果，Probe-Capture宏基因组学的一致性率为91.8%(169/184)，灵敏度为100%，特异性为87.1%。在临床影响方面，64例（34.8%）患者根据Probe-Capture宏基因组学的结果调整了抗生素治疗，41例（22.3%）患者出现了>；抗生素调整后SOFA评分下降2分。结论与传统的宏基因组学相比，探针捕获宏基因组学显著提高了病原体的检测能力。与脓毒症患者的血培养和RT-PCR相比，它可以改善抗生素治疗并改善患者预后。这项研究首次通过整合抗生素调整和SOFA评分变化来评估宏基因组测序的临床影响，表明大约五分之一的脓毒症患者受益于这种先进的诊断方法。本研究已于2018年11月30日在临床试验（clinicaltrials.gov）上注册，注册号为NCT03760315。Probe-Capture宏基因组阳性率明显高于血培养(51.6% vs. 17.4%, p <；措施)。结合血培养和RT-PCR结果，Probe-Capture宏基因组一致性达到91.8%。34.8%的患者根据Probe-Capture宏基因组结果调整了抗生素，22.3%的患者SOFA评分下降2分以上。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.