通过临床宏基因组测序改善脓毒症或脓毒性休克中的病原体鉴定。

Improved pathogen identification in sepsis or septic shock by clinical metagenomic sequencing.

作者信息

Brenner Thorsten, Decker Sebastian O, Vainshtein Yevhen, Grumaz Silke, Manoochehri Mehdi, Feißt Manuel, Seidel-Glätzer Andrea, Pletz Mathias W, Bracht Hendrik, Berger Marc M, Fuest Kristina, Blobner Manfred, Bach Friedhelm, Moerer Onnen, Brandenburger Timo, Dimski Thomas, Suchodolski Klaudiusz, Jäkel Ulrike, Zischkau Jana, Häberle Helene, Rosenberger Peter, Schürholz Tobias, Lindau Simone, Schaller Stefan J, Putensen Christian, Dusse Fabian, Petros Sirak, Gaasch Max, Nusshag Christian, Weigand Markus A, Sohn Kai

机构信息

Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.

Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany.

出版信息

J Infect. 2025 Sep;91(3):106565. doi: 10.1016/j.jinf.2025.106565. Epub 2025 Aug 6.

DOI:10.1016/j.jinf.2025.106565

PMID:40774415

Abstract

OBJECTIVES

Despite limited sensitivity and specificity, blood cultures (BCs) still represent the gold standard of diagnostic care in septic patients. We aimed to overcome current diagnostic limitations by unbiased next-generation sequencing (NGS) of circulating microbial cell-free DNA (mcfDNA) in plasma samples.

METHODS

We performed a prospective, observational, non-interventional, multicenter study (Next GeneSiS-Trial) to compare positivity rates for NGS-based identification of causative pathogens with BCs in patients suffering from sepsis or septic shock. An independent expert panel (n=3) retrospectively evaluated the plausibility of NGS-based findings and the potential for anti-infective treatment adaptations based on NGS results.

RESULTS

The positivity rate of NGS-based diagnostics (NGS+) for 491 septic patients was 70.5% compared to positive BCs (BC+) with 19.4% within the first three days after sepsis onset. NGS+ results were evaluated as plausible in 98.6% of cases by the expert panel. Based on the experts´ recommendations, additional knowledge of NGS-based pathogen findings would have resulted in anti-infective treatment adaptations in 32.6% of all patients. Potentially inadequately treated NGS+/blood culture negative (BC-) patients showed worse outcomes.

CONCLUSION

The integration of NGS-based pathogen diagnostics in sepsis has the potential to improve patients´ outcomes as compared to a treatment strategy based on standard-of-care microbiological diagnostics alone.

摘要

目的

尽管血培养（BC）的敏感性和特异性有限，但它仍然是脓毒症患者诊断护理的金标准。我们旨在通过对血浆样本中循环微生物游离DNA（mcfDNA）进行无偏倚的下一代测序（NGS）来克服当前的诊断局限性。

方法

我们开展了一项前瞻性、观察性、非干预性的多中心研究（Next GeneSiS试验），以比较脓毒症或脓毒性休克患者中基于NGS鉴定致病病原体的阳性率与血培养的阳性率。一个独立的专家小组（n = 3）回顾性评估了基于NGS的结果的合理性以及根据NGS结果调整抗感染治疗的可能性。

结果

491例脓毒症患者中，基于NGS的诊断（NGS+）阳性率为70.5%，而脓毒症发作后头三天内血培养阳性（BC+）率为19.4%。专家小组在98.6%的病例中认为NGS+结果合理。根据专家的建议，基于NGS的病原体检测结果的额外信息将导致32.6%的所有患者调整抗感染治疗。NGS+/血培养阴性（BC-）且可能治疗不充分的患者预后较差。