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[NEJM发表论文]:临床宏基因测序诊断脑膜炎与脑炎
2019年06月17日 时讯速递, 进展交流 暂无评论

ORIGINAL ARTICLE

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis

Michael R. Wilson, Hannah A. Sample, Kelsey C. Zorn, et al

N Engl J Med 2019; 380:2327-2340
DOI: 10.1056/NEJMoa1803396 

Abstract

BACKGROUND 背景

Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.

脑脊液(CSF)的宏基因二代测序(NGS)能够通过一次检测鉴别多种致病微生物。

METHODS 方法

In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.

在为期一年的多中心前瞻研究中,我们将CSF的宏基因NGS用于诊断住院患者的感染性脑膜炎及脑炎。宏基因NGS中所有阳性结果通过正交试验室检测确证。通过临床微生物测序理事会的电话会议以及调查得到医生的反馈。通过回顾查阅病例评价临床作用。

RESULTS 结果

We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.

我们在8家医院入选了204名儿童及成年患者。患者病情危重:48.5%收入ICU,30天病死率11.3%。共有57名(27.9%)患者确诊58例神经系统感染。这58例感染中的13例(22%)能够宏基因NGS鉴别,但未能根据医院的临床检测确诊。宏基因NGS能够诊断其余45例(78%)感染中的19例。在宏基因NGS未能诊断的26例感染中,11例仅通过血清学检测确诊,7例通过CSF以外的组织标本确诊,8例因CSF中致病微生物滴度过低导致宏基因NGS结果阴性。在仅通过宏基因NGS确诊的13例感染患者中,8例可能具有临床作用,13例中7例具有指导治疗的作用。

CONCLUSIONS 结论

Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.)

常规微生物检查常常不足以检测所有的神经侵袭性致病微生物。本研究发现,针对脑膜炎和脑炎患者CSF进行宏基因NGS,能够提高神经系统感染的诊断率,并在某些病例提供有用信息。

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