基于游离血浆细胞的宏基因组下一代测序对感染性疾病诊断的临床影响：一项多中心回顾性队列研究。

Clinical Impact of Metagenomic Next-Generation Sequencing of Plasma Cell-Free DNA for the Diagnosis of Infectious Diseases: A Multicenter Retrospective Cohort Study.

机构信息

Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

Clinical Microbiology Laboratory, Stanford Health Care, Stanford, California, USA.

出版信息

Clin Infect Dis. 2021 Jan 27;72(2):239-245. doi: 10.1093/cid/ciaa035.

DOI:10.1093/cid/ciaa035

PMID:31942944

Abstract

BACKGROUND

Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA has emerged as an attractive diagnostic modality allowing broad-range pathogen detection, noninvasive sampling, and earlier diagnosis. However, little is known about its real-world clinical impact as used in routine practice.

METHODS

We performed a retrospective cohort study of all patients for whom plasma mNGS (Karius test) was performed for all indications at 5 United States institutions over 1.5 years. Comprehensive records review was performed, and standardized assessment of clinical impact of the mNGS based on the treating team's interpretation of Karius results and patient management was established.

RESULTS

A total of 82 Karius tests were evaluated from 39 (47.6%) adults and 43 (52.4%) children and a total of 53 (64.6%) immunocompromised patients. Karius positivity rate was 50 of 82 (61.0%), with 25 (50.0%) showing 2 or more organisms (range, 2-8). The Karius test results led to positive impact in 6 (7.3%), negative impact in 3 (3.7%), and no impact in 71 (86.6%), and was indeterminate in 2 (2.4%). Cases with positive Karius result and clinical impact involved bacteria and/or fungi but not DNA viruses or parasites. In 10 patients who underwent 16 additional repeated tests, only 1 was associated with clinical impact.

CONCLUSIONS

The real-world impact of the Karius test as currently used in routine clinical practice is limited. Further studies are needed to identify high-yield patient populations, define the complementary role of mNGS to conventional microbiological methods, and discern how best to integrate mNGS into current testing algorithms.

摘要

背景

血浆无细胞游离 DNA 的宏基因组下一代测序（mNGS）已成为一种有吸引力的诊断方式，可实现广泛的病原体检测、非侵入性采样和更早的诊断。然而，关于其在常规实践中使用的实际临床影响知之甚少。

方法

我们对在 1.5 年内美国 5 个机构对所有适应证进行血浆 mNGS（Karius 测试）的所有患者进行了回顾性队列研究。对全面的记录进行了审查，并根据治疗团队对 Karius 结果的解释和患者管理对 mNGS 的临床影响进行了标准化评估。

结果

共评估了 39 名成人（47.6%）和 43 名儿童（52.4%）和 53 名免疫功能低下患者（64.6%）的 82 次 Karius 测试。Karius 阳性率为 50 例（61.0%），25 例（50.0%）显示 2 种或更多种病原体（范围 2-8）。Karius 测试结果导致 6 例（7.3%）产生积极影响、3 例（3.7%）产生消极影响、71 例（86.6%）无影响，2 例（2.4%）结果不确定。Karius 阳性结果和临床影响的病例涉及细菌和/或真菌，但不涉及 DNA 病毒或寄生虫。在 10 名接受了 16 次重复测试的患者中，只有 1 次与临床影响相关。