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市级医院临床宏基因组下一代测序对疑似中枢神经系统感染的诊断性能:一项中国的回顾性研究

Diagnostic Performance of Clinical Metagenomic Next-Generation Sequencing for Suspected Central Nervous System Infections in a Municipal Hospital: A Retrospective Study in China.

作者信息

Wang Huimin, Zhao Jianting, Wang Xueyao, Li Miaomiao, Hu Tiantian, Xu Huan, Dong Min, He Wenlong, Che Zhenyong

机构信息

Special Need Wards (Department of Neurology and Geriatrics), Xinxiang Central Hospital, Xinxiang, Henan Province, People's Republic of China.

Department of Neurology, the Fourth Clinical College of Xinxiang Medical University, Xinxiang, Henan Province, People's Republic of China.

出版信息

Infect Drug Resist. 2025 May 22;18:2637-2652. doi: 10.2147/IDR.S500279. eCollection 2025.

Abstract

PURPOSE

Cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) has the potential to identify the majority of pathogens in a single test. Accurate pathogen identification is vital for central nervous system infection (CNSi). However, there are few related studies investigating in a municipal hospital.

PATIENTS AND METHODS

A total of 52 suspected CNSi patients were retrospectively recruited in Xinxiang central hospital between July 2019 and April 2023. The diagnostic performance of CSF mNGS, conventional microbiological tests (CMT), and the combination of CSF mNGS and CMT were evaluated by comparing to the final diagnosis.

RESULTS

Among 52 suspected CNSi patients, 35 were diagnosed as CNSi. In comparison to the final diagnosis, the area under curves (AUC) for CSF CMT, CSF mNGS, and the combination of CMT and mNGS for the diagnosis of CNSi were 0.56 (95% CI 0.4-0.72), 0.74 (95% CI 0.61-0.84), and 0.76 (95% CI 0.63-0.88), respectively. The sensitivities were 11.43% (95% CI 4.54%-25.95%), 48.57% (95% CI 32.99%-64.43%), and 51.43% (95% CI 35.57%-67.01%), respectively. The accuracy was 40.38 (95% CI 27.01%-54.90%), 65.38% (95% CI 50.91%-78.03%), and 67.31% (95% CI 52.89%-79.67%), respectively. Furthermore, based on CSF mNGS results, seven patients confirmed initial treatment, two escalated, and one de-escalated. Additionally, we identified the optimal cutoff values as 1.75 U/L for CSF adenosine deaminase (ADA), 75.44 U/L for CSF protein, and 185 mmHO for CSF pressure, when these values were exceeded, CSF mNGS tended to yield positive results.

CONCLUSION

CSF mNGS showed superior diagnostic performance in CNSi and hence could serve as a complementary tool to CMT and conjunctively guide the precision therapy. Additionally, the values for CSF ADA, protein and pressure could assist in predicting mNGS positive result. With technical improvements for mNGS sample processing to increase throughput and reduce costs, clinicians may use mNGS more widely in municipal hospital laboratories.

摘要

目的

脑脊液宏基因组下一代测序(mNGS)有潜力在一次检测中识别出大多数病原体。准确识别病原体对于中枢神经系统感染(CNSi)至关重要。然而,在市级医院中对此进行研究的相关研究较少。

患者与方法

回顾性纳入2019年7月至2023年4月在新乡市中心医院的52例疑似CNSi患者。通过与最终诊断结果比较,评估脑脊液mNGS、传统微生物学检测(CMT)以及脑脊液mNGS与CMT联合检测的诊断性能。

结果

52例疑似CNSi患者中,35例被诊断为CNSi。与最终诊断相比,脑脊液CMT、脑脊液mNGS以及CMT与mNGS联合检测用于诊断CNSi的曲线下面积(AUC)分别为0.56(95%CI 0.4 - 0.72)、0.74(95%CI 0.61 - 0.84)和0.76(95%CI 0.63 - 0.88)。敏感性分别为11.43%(95%CI 4.54% - 25.95%)、48.57%(95%CI 32.99% - 64.43%)和51.43%(95%CI 35.57% - 67.01%)。准确性分别为40.38(95%CI 27.01% - 54.90%)、65.38%(95%CI 50.91% - 78.03%)和67.31%(95%CI 52.89% - 79.67%)。此外,基于脑脊液mNGS结果,7例患者确认初始治疗方案,2例升级,1例降级。另外,我们确定脑脊液腺苷脱氨酶(ADA)的最佳临界值为1.75 U/L,脑脊液蛋白为75.44 U/L,脑脊液压力为185 mmH₂O,当超过这些值时,脑脊液mNGS往往会得出阳性结果。

结论

脑脊液mNGS在CNSi诊断中表现出卓越的诊断性能,因此可作为CMT的补充工具,并联合指导精准治疗。此外,脑脊液ADA、蛋白和压力的值有助于预测mNGS阳性结果。随着mNGS样本处理技术的改进以提高通量并降低成本,临床医生可能会在市级医院实验室更广泛地使用mNGS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db79/12106916/3cecc47d4d2a/IDR-18-2637-g0001.jpg

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