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微生物培养、宏基因组新一代测序和液滴数字聚合酶链反应方法在神经外科中枢神经系统感染患者病原体检测中的比较

Comparison of microbial culture, metagenomic next-generation sequencing and droplet digital polymerase chain reaction methods for pathogen detection in patients with neurosurgical central nervous system infection.

作者信息

Yu Hai, Liang Dong, Ding Xiangqian, Gao Han, Fan Guoyuan, Song Yan, Sun Shoujia, Huang Qibing, Liu Shili, Zhang Zeli

机构信息

Department of Emergency Neurosurgical Intensive Care Unit, Qilu Hospital of Shandong University and Brain Science Research Institute of Shandong University, Jinan, Shandong, China.

Department of Medical Microbiology, School of Basic Medical Sciences, Cheelo College of Medicine, Shandong University, Jinan, Shandong, China.

出版信息

Front Cell Infect Microbiol. 2025 Jul 30;15:1606283. doi: 10.3389/fcimb.2025.1606283. eCollection 2025.


DOI:10.3389/fcimb.2025.1606283
PMID:40809522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12343261/
Abstract

BACKGROUND: Neurosurgical central nervous system infections (NCNSIs) are one of the most common complications in neurosurgical patients, followed by neurosurgery itself, trauma, implants or infection need to be treated by surgery. However, the diagnosis of NCNSIs continues to pose a significant challenge. The primary objective of this study was to comprehensively assess the diagnostic performance of metagenomic next-generation sequencing (mNGS) and Multiplex Droplet Digital PCR (ddPCR) in elucidating the microbiological etiologies underlying NCNSIs in affected patients. METHODS: Data on 127 enrolled NCNSIs patients were collected from Emergency Neurosurgical Intensive Care Unit at Qilu Hospital of Shandong University from June 2022 to October 2024. The clinical record, cerebrospinal fluid or pus routine, biochemical tests, microbial smear and culture, mNGS and ddPCR results, time to positive culture(TTPC), time from sample harvesting to final positive results (THTR) obtained by the physician, turn-around time for mNGS and ddPCR, and follow-up data were collected and analyzed. RESULTS: A total of 127 patients were enrolled in this study. In comparison to the positive rate achieved by traditional culture method (59.1%) in diagnosing NCNSIs, the overall pathogen detection rates of mNGS and ddPCR were markedly elevated (86.6%, <0.01 and 78.7%, <0.01, respectively). Notably, the administration of empiric antibiotics did not significantly influence the positive detection rates of either mNGS or ddPCR. When stratified by infection type, mNGS and ddPCR demonstrated notably higher positive detection rates in three specific categories of NCNSIs-ventriculitis, intracranial abscess, and implant-associated infections-compared to meningitis. Among the 127 patients, 37 (29.1%) tested positive via mNGS but negative via microbial culture, whereas 11 patients were positive via mNGS but negative via ddPCR. The mean TTPC for microbial culture was 15.1 ± 10.4 hours. Furthermore, the mean THTR for microbial culture, mNGS and ddPCR were 22.6 ± 9.4 hours, 16.8 ± 2.4 hours and 12.4 ± 3.8 hours, respectively. Importantly, ddPCR exhibited a significantly shorter THTR compared to mNGS (<0.01). CONCLUSION: mNGS and ddPCR hold the potential to substantially augment the diagnostic efficacy for NCNSIs patients. It is advisable that, in future clinical practice, mNGS and ddPCR be more extensively employed for the early and precise identification of pathogens in NCNSIs patients.

摘要

背景:神经外科中枢神经系统感染(NCNSIs)是神经外科患者最常见的并发症之一,仅次于神经外科手术本身、创伤、植入物或需要手术治疗的感染。然而,NCNSIs的诊断仍然面临重大挑战。本研究的主要目的是全面评估宏基因组下一代测序(mNGS)和多重液滴数字PCR(ddPCR)在阐明受影响患者NCNSIs潜在微生物病因方面的诊断性能。 方法:收集2022年6月至2024年10月山东大学齐鲁医院神经外科急诊重症监护病房收治的127例NCNSIs患者的数据。收集并分析临床记录、脑脊液或脓液常规、生化检查、微生物涂片和培养、mNGS和ddPCR结果、培养阳性时间(TTPC)、从样本采集到医生获得最终阳性结果的时间(THTR)、mNGS和ddPCR的周转时间以及随访数据。 结果:本研究共纳入127例患者。与传统培养方法诊断NCNSIs的阳性率(59.1%)相比,mNGS和ddPCR的总体病原体检测率显著提高(分别为86.6%,<0.01和78.7%,<0.01)。值得注意的是,经验性使用抗生素对mNGS或ddPCR的阳性检测率没有显著影响。按感染类型分层时,与脑膜炎相比,mNGS和ddPCR在三种特定类型的NCNSIs(脑室炎、颅内脓肿和植入物相关感染)中的阳性检测率显著更高。在127例患者中,37例(29.1%)通过mNGS检测呈阳性但微生物培养呈阴性,而11例患者通过mNGS检测呈阳性但ddPCR检测呈阴性。微生物培养的平均TTPC为15.1±10.4小时。此外,微生物培养、mNGS和ddPCR的平均THTR分别为22.6±9.4小时、16.8±2.4小时和12.4±3.8小时。重要的是,与mNGS相比,ddPCR的THTR显著缩短(<0.01)。 结论:mNGS和ddPCR有可能显著提高NCNSIs患者的诊断效率。建议在未来的临床实践中,更广泛地应用mNGS和ddPCR对NCNSIs患者进行病原体的早期精确鉴定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7624e5fa1e31/fcimb-15-1606283-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7fc06b84c41c/fcimb-15-1606283-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7b84fd9e3039/fcimb-15-1606283-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7194a4ae69b5/fcimb-15-1606283-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/856610f255f5/fcimb-15-1606283-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/14f5b48dc7a1/fcimb-15-1606283-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7624e5fa1e31/fcimb-15-1606283-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7fc06b84c41c/fcimb-15-1606283-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7b84fd9e3039/fcimb-15-1606283-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7194a4ae69b5/fcimb-15-1606283-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/856610f255f5/fcimb-15-1606283-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/14f5b48dc7a1/fcimb-15-1606283-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c0/12343261/7624e5fa1e31/fcimb-15-1606283-g006.jpg

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本文引用的文献

[1]
Early and Accurate Pathogen Identification Based on mNGS: Key to Timely Therapy for Mycoplasma Prosthetic Joint Infection.

Orthop Surg. 2025-7

[2]
Symptomatic central nervous system infections in kidney transplant recipients: a 20-years multicenter observational study.

BMC Infect Dis. 2025-5-1

[3]
Plasma cell-free DNA Droplet Digital PCR provides rapid and efficient infectious microbiology diagnosis for febrile haematological patients.

Front Cell Infect Microbiol. 2025-2-19

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Microbiol Spectr. 2025-4

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BMC Infect Dis. 2025-1-6

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Respir Res. 2024-10-5

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BMC Vet Res. 2024-8-26

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Neurosurg Rev. 2024-1-29

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