血流感染病原体分子检测技术研究进展

郑皓; 陈小萍; 卢金星

doi:10.3784/j.issn.1003-9961.2020.11.018

引用本文: 郑皓, 陈小萍, 卢金星. 血流感染病原体分子检测技术研究进展[J]. 疾病监测. DOI: 10.3784/j.issn.1003-9961.2020.11.018 shu

Citation: Hao Zheng, Xiaoping Chen and Jinxing Lu. Progress in research of molecular detection of pathogens in bloodstream infection[J]. Disease Surveillance. DOI: 10.3784/j.issn.1003-9961.2020.11.018 shu

血流感染病原体分子检测技术研究进展

郑皓 ^, ,
陈小萍 ^{,

,} ,
卢金星 ^{,

,}

中国疾病预防控制中心传染病预防控制所，传染病预防控制国家重点实验室，感染性疾病诊治协同创新中心，北京 102206

作者简介: 郑皓，女，北京市人，在读硕士研究生，主要从事院内感染相关病原菌研究工作，Email：zhenghao@icdc.cn;

通信作者: 陈小萍, chenxiaoping@icdc.cn 卢金星, lujinxing@icdc.cn

基金项目: 国家科技重大专项（No. 2018ZX10733402）

摘要: 血流感染（BSI）的发病率在世界范围内有逐年升高趋势，早期识别与诊断BSI对临床治疗意义重大。快速诊断BSI的分子学方法分为2类，即全血检测方法和依赖于血培养的检测方法。与血培养方法相比，全血检测方法缩短了检测时间，可以检测难培养的病原菌，但敏感性仍需提高。本研究对BSI病原体分子检测技术的研究进展予以综述。

关键词:

血流感染 /
脓毒症 /
分子检测

English

Progress in research of molecular detection of pathogens in bloodstream infection

Hao Zheng ^, ,
Xiaoping Chen ^{,

,} ,
Jinxing Lu ^{,

,}

State Key Laboratory of Communicable Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing 102206, China

Corresponding author: Xiaoping Chen, chenxiaoping@icdc.cn Jinxing Lu, lujinxing@icdc.cn

Received Date: 2020-04-29
Available Online: 2020-11-30
Fund Project: This work was supported by the National Science and Technology Major Project of China (No. 2018ZX10733402)

Abstract: The incidence rate of bloodstream infection (BSI) continues to increase around the world. The early identification and diagnosis of BSI has a great significance for clinical therapy. There are two kinds of molecular methods for rapid diagnosis of BSI: blood culture dependent detection and whole blood detection. Compared with the blood culture, whole blood detection can shorten the time needed and identify the pathogens which are difficult to culture, but the sensitivity needs to be improved. This paper summarizes the progress in the molecular detection of pathogens in bloodstream infection.

Key words:

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表 1 本综述涉及的血流感染病原体快速检测商业化仪器/方法

Table 1. Commercial instruments/methods for rapid detection of pathogens in bloodstream infection in this review

仪器（制造商）	原理	检测样本	检测耐药基因靶点数/方法	检测病原菌	检测时间	操作时间	敏感性（%）	特异性（%）	参考文献
AdvanDx QuickFISH^® （AdvanDx，MA）	FISH	血培养	0	（1）2个革兰阳性菌种靶点（2）3个革兰阴性菌种靶点（3）肠球菌（粪肠球菌，屎肠球菌或其他肠球菌）（4）3个真菌种靶点	<30 min	<5 min	（1）97.1～100 （2）85.8～100 （3）97.0～98.3 （4）98.3～100	（1）89.5～100 （2）94.8～99.6 （3）100 （4）99.4～100	［6, 9］
Accelerate Pheno™ System - PhenoTest™ BC（Accelerate Diagnostics，USA）	FISH+MCA	血培养	MCA鉴定	6个属/种革兰阳性球菌，8个属/种革兰阴性杆菌，2种真菌	<1.5 h （AST <7 h）	2 min	88.2～100	97.6～100	［10–11］
BD MAX™ MRSA StaphSR（BD，USA）	多重荧光定量PCR技术	血培养	1	MSSA，MRSA	2 h	<1 min	97.9～100	98.1～100	［14］
Magicplex^TM Sepsis Test（SeeGene，Korea）	多重荧光定量PCR技术	全血	3	属水平检测90余种细菌和真菌（73种革兰阳性菌，12种革兰阴性菌，6种真菌），种水平检测27种细菌和真菌	6 h	−	37～65	77～92	［15］
Prove-it™ Sepsis（Mobidiag，Finland）	PCR+ Microarray	血培养	1	60种细菌，13种真菌	3 h	−	94.7～99	98	［17］
Luminex nanosphere VERIGENE^®（Nanosphere，USA）	PCR+ Microarray	血培养	4（革兰阳性菌）；6（革兰阴性菌）	13个革兰阳性菌属/种靶点；9个革兰阴性菌属/种靶点	2.5 h	10 min	92.6～98.6	95.4～99.5	［22］
Biofire^® FilmArray^® BCID Panel（BioFire Diagnostics，USA）	PCR+ Microarray	血培养	3	8个革兰阳性菌属/种靶点，11个革兰阴性菌属/种靶点，5个真菌种靶点	1 h	<5 min	89.4～91.6	100	［24–25］
ePlex^® BCID（GenMark Diagnostics，USA）	PCR+ Microarray	血培养	4（革兰阳性菌）；6（革兰阴性菌）	20个革兰阳性菌属/种靶点，pan-GN，pan-Candida；21个革兰阴性菌属/种靶点，pan-GP，pan-Candida；16个真菌属/种靶点	1.5 h	<2 min	97～99	−	［27］
Curetis Unyvero™ BCU（Curetis GmbH，USA）	PCR+ Microarray	血培养	16	>50种细菌和真菌（28个细菌属/种靶点，8个真菌属/种靶点）	4～5 h	<2 min	96.8	99.8	［28］
LightCycler^® SeptiFast（Roche Diagnostics，Switzerland）	PCR+ Microarray	全血	1	25个细菌和真菌属/种靶点	4.5 h	−	68～86	65～86	［29］
sepsiTest^®（Molzym，Germany）	PCR+ Sequencing	全血	0	345种细菌和真菌	8～12 h	−	87	86	［36］
iDTECT^TM Dx Blood test（PathoQuest SAS，France）	NGS	全血	0	800种细菌和400种病毒	−	−	−	−	［40］
MALDI-TOF MS（Bruker Daltonics，Germany 或 bioMérieux，France）	MALDI-TOF MS	血培养	0	−	1 h	−	76～98	>96	［42］
PLEX-ID-BAC Spectrum assay（Abbott，USA）	PCR+ESI-MS	全血	4	800种细菌和真菌	6 h	−	83	94	［48］
T2Dx® - T2Candida^® & T2Bacteria^®（T2Biosystems，USA）	PCR+NMR	全血	0	（1）5种真菌（2）6种细菌	3～5 h	5 min	（1）96.4 （2）90	（1）99.4 （2）90	［51］
PID panel（HelixBind，USA）	γPNAs	全血	0	21种细菌和真菌	<2.5 h	−	95.5	89.5	［52］
注：FISH. 荧光原位杂交；MCA. 细胞形态动力学分析；Microarray. 微阵列；NGS. 第二代测序技术；ESI-MS. 电喷雾离子化质谱；NMR. 核磁共振；γPNAs. γ-修饰肽核酸；MSSA. 甲氧西林敏感金黄色葡萄球菌；MRSA. 耐甲氧西林金黄色葡萄球菌；−. 无数据

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表 2 血流感染病原体分子学检测方法优缺点

Table 2. Advantages and disadvantages of molecular detection of pathogens in bloodstream infection

方法	优　　点	缺　　点
荧光原位杂交技术	无需扩增，不易受血液基质的抑制和污染	缺乏抗菌药物敏感性信息
荧光定量PCR技术	灵敏度高，特异性强	仪器通道数受限，诊断范围较窄，缺乏抗菌药物敏感性信息
多重PCR技术	成本低，通量高	灵敏度和/或特异性较低
微阵列技术	速度快，通量高，可检测多个耐药基因靶点	受背景分辨率影响
第二代测序技术	成本低，通量高，可检测多个耐药基因靶点	受背景分辨率影响
质谱技术	速度快，通量高	对蛋白质的丰度和纯度要求高，数据库需完善

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0161：血流感染分子检测技术研究进展.docx

0161：血流感染病原体分子检测技术研究进展.docx

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通信作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

血流感染病原体分子检测技术研究进展

作者简介: 郑皓，女，北京市人，在读硕士研究生，主要从事院内感染相关病原菌研究工作，Email：zhenghao@icdc.cn;

通信作者: 陈小萍, chenxiaoping@icdc.cn 卢金星, lujinxing@icdc.cn

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Progress in research of molecular detection of pathogens in bloodstream infection

Corresponding author: Xiaoping Chen, chenxiaoping@icdc.cn Jinxing Lu, lujinxing@icdc.cn

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通信作者: 陈斌, bchen63@163.com