Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis
Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis
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DOI：
10.1056/nejmoa1803396
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发表时间：
2019-06-13
影响因子：
158.5
通讯作者：
Chiu, C. Y.
中科院分区：
文献类型：
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作者：
Wilson, M. R.;Sample, H. A.;Chiu, C. Y.
背景脑脊液（CSF）宏基因组下一代测序（NGS）有可能在一次测试中识别广泛的病原体。方法采用1年多中心前瞻性研究方法，探讨脑脊液宏基因组NGS对感染性脑膜炎和脑炎的诊断价值。对宏基因组NGS的病原体的所有阳性测试通过正交实验室测试来确认。通过与临床微生物测序委员会的电话会议和调查来获得医生反馈。采用回顾性病历评价临床疗效。结果我们在八家医院招募了204名儿童和成人患者。患者病情严重：48.5%进入重症监护室，所有研究患者的30天死亡率为11.3%。57例患者（27.9%）共诊断出58例神经系统感染。在这58例感染中，宏基因组NGS确定了13例（22%），这些感染在来源医院的临床检测中没有被发现。在其余45例感染（78%）中，宏基因组NGS在19例中进行了并发诊断。在未通过宏基因组NGS鉴定的26例感染中，11例仅通过血清学检测诊断，7例从CSF以外的组织样本诊断，8例由于CSF中病原体滴度低而在宏基因组NGS上呈阴性。仅通过宏基因组NGS进行的13项诊断中有8项具有可能的临床效果，其中7项指导治疗。结论常规微生物学检测通常不足以检测所有神经侵袭性病原体。在这项研究中，从脑膜炎或脑炎患者获得的CSF的宏基因组NGS改善了神经系统感染的诊断，并在某些情况下提供了可操作的信息。（由美国国立卫生研究院和其他机构资助; PDAID ClinicalTrials.gov编号，NCT 02910037。
Background Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. Methods 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. Results 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. Conclusions 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.)