Application of nanopore sequencing in bloodstream infection_West China Medical Journal

Authors：

WU Zegang ¹ , GU Jian ² , ZHENG Hongyun ¹ , XU Wanzhou ² ,  XIAO Hongjun ³ ,  TONG Yongqing ^1,2

1. Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P. R. China;
2. Clinical Molecular Diagnostics of Wuhan University, Wuhan, Hubei 430060, P. R. China;
3. Medical Vocational and Technical School of Wuhan University, Wuhan, Hubei 430060, P. R. China;

Corresponding author：

XIAO Hongjun, Email: xhj1969@163.com; TONG Yongqing, Email: tytsing@whu.edu.cn

Keywords：

Bloodstream infection; pathogen; nanopore sequencing; blood culture

DOI：

10.7507/1002-0179.202206082

Video：

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Objective To evaluate the basic performance and clinical application value of nanopore sequencing, in order to provide new ideas for the rapid detection of clinical etiology. Methods From December 2021 to May 2022, blood samples from inpatients suspected of bloodstream infection in Renmin Hospital of Wuhan University were collected, and the nanopore sequencing platform and blood culture method were used to simultaneously identify the pathogenic bacteria in the blood samples of the selected patients, and identify the pathogenic bacteria in the blood samples of the selected patients. The basic performance and clinical utility of nanopore sequencing were evaluated. Results A total of 251 patients were included, and 119 patients (47.4%) were found to have pathogens by nanopore sequencing, which was higher than that of 23 patients (9.2%) by blood culture (χ²=79.167, P<0.001). The results of the two methods are not consistent (kappa=0.052, P=0.175). Nanopore sequencing has a certain missed detection rate. In terms of the types of pathogenic bacteria detected, 47 bacteria and 15 fungi were detected by nanopore sequencing. Conclusion Compared with blood culture, nanopore sequencing has a higher detection rate and more types of pathogens. This technology has obvious advantages in the rapid diagnosis of bloodstream infection pathogens.

Citation： WU Zegang, GU Jian, ZHENG Hongyun, XU Wanzhou, XIAO Hongjun, TONG Yongqing. Application of nanopore sequencing in bloodstream infection. West China Medical Journal, 2022, 37(8): 1166-1169. doi: 10.7507/1002-0179.202206082 Copy

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2.	Goto M, Al-Hasan MN. Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe. Clin Microbiol Infect, 2013, 19(6): 501-509.
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4.	Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med, 2017, 43(3): 304-377.
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6.	张家源, 陈玉梅, 邹尧, 等. 重症血液病患儿血流感染的临床分析. 中华医院感染学杂志, 2014(20): 5136-5138.
7.	郭鹰, 江代红, 郭富饶. 血流感染的实验室诊断技术进展. 实用医学杂志, 2021, 37(17): 2300-2303.
8.	刘晔, 许小毛. 基于纳米孔测序技术的临床检测研究进展. 中华检验医学杂志, 2022, 45(3): 296-299.
9.	Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control, 1988, 16(3): 128-140.
10.	Costa SP, Dias NM, Melo LDR, et al. A novel flow cytometry assay based on bacteriophage-derived proteins for Staphylococcus detection in blood. Sci Rep, 2020, 10(1): 6260.
11.	Mehl A, Åsvold BO, Lydersen S, et al. Burden of bloodstream infection in an area of Mid-Norway 2002-2013: a prospective population-based observational study. BMC Infect Dis, 2017, 17(1): 205.
12.	Liu V, Escobar GJ, Greene JD, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA, 2014, 312(1): 90-92.
13.	范帅华, 杜鹏程, 郭军. 纳米孔测序技术在呼吸系统感染病原学诊断中的应用价值与展望. 中华医学杂志, 2021, 101(25): 2013-2015.
14.	Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases. Clin Infect Dis, 2018, 66(5): 778-788.
15.	Opota O, Jaton K, Greub G. Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood. Clin Microbiol Infect, 2015, 21(4): 323-331.
16.	王玉静, 陆梓涔, 陈俊煜, 等. 高通量测序技术的发展及其在临床检测中的应用. 厦门大学学报(自然科学版), 2021, 60(5): 811-820.
17.	中华医学会检验医学分会临床微生物学组, 中华医学会微生物学与免疫学分会临床微生物学组, 中国医疗保健国际交流促进会临床微生物与感染分会. 宏基因组高通量测序技术应用于感染性疾病病原检测中国专家共识. 中华检验医学杂志, 2021, 44(2): 107-120.
18.	叶福强, 李鹏, 韩一芳, 等. 基于纳米孔测序技术的呼吸道病原体快速确认. 分子诊断与治疗杂志, 2020, 12(2): 127-132, 150.
19.	李丽, 金力, 朱咏臻, 等. 2014-2019 年某医院血流感染患者的临床特征和病原学分析. 中国抗生素杂志, 2022, 47(1): 84-89.
20.	Wang K, Li P, Lin Y, et al. Metagenomic diagnosis for a culture-negative sample from a patient with severe pneumonia by nanopore and next-generation sequencing. Front Cell Infect Microbiol, 2020, 10: 182.
21.	Charalampous T, Kay GL, Richardson H, et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol, 2019, 37(7): 783-792.

1. Lamy B, Sundqvist M, Idelevich EA, et al. Bloodstream infections - standard and progress in pathogen diagnostics. Clin Microbiol Infect, 2020, 26(2): 142-150.
2. Goto M, Al-Hasan MN. Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe. Clin Microbiol Infect, 2013, 19(6): 501-509.
3. Pliakos EE, Andreatos N, Shehadeh F, et al. The cost-effectiveness of rapid diagnostic testing for the diagnosis of bloodstream infections with or without antimicrobial stewardship. Clin Microbiol Rev, 2018, 31(3): e00095-17.
4. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med, 2017, 43(3): 304-377.
5. 梁蓓, 姜利, 刘淑梅, 等. 首都医科大学附属复兴医院 2012 年住院患者血流感染分析. 中华内科杂志, 2016, 55(8): 609-612.
6. 张家源, 陈玉梅, 邹尧, 等. 重症血液病患儿血流感染的临床分析. 中华医院感染学杂志, 2014(20): 5136-5138.
7. 郭鹰, 江代红, 郭富饶. 血流感染的实验室诊断技术进展. 实用医学杂志, 2021, 37(17): 2300-2303.
8. 刘晔, 许小毛. 基于纳米孔测序技术的临床检测研究进展. 中华检验医学杂志, 2022, 45(3): 296-299.
9. Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control, 1988, 16(3): 128-140.
10. Costa SP, Dias NM, Melo LDR, et al. A novel flow cytometry assay based on bacteriophage-derived proteins for Staphylococcus detection in blood. Sci Rep, 2020, 10(1): 6260.
11. Mehl A, Åsvold BO, Lydersen S, et al. Burden of bloodstream infection in an area of Mid-Norway 2002-2013: a prospective population-based observational study. BMC Infect Dis, 2017, 17(1): 205.
12. Liu V, Escobar GJ, Greene JD, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA, 2014, 312(1): 90-92.
13. 范帅华, 杜鹏程, 郭军. 纳米孔测序技术在呼吸系统感染病原学诊断中的应用价值与展望. 中华医学杂志, 2021, 101(25): 2013-2015.
14. Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases. Clin Infect Dis, 2018, 66(5): 778-788.
15. Opota O, Jaton K, Greub G. Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood. Clin Microbiol Infect, 2015, 21(4): 323-331.
16. 王玉静, 陆梓涔, 陈俊煜, 等. 高通量测序技术的发展及其在临床检测中的应用. 厦门大学学报(自然科学版), 2021, 60(5): 811-820.
17. 中华医学会检验医学分会临床微生物学组, 中华医学会微生物学与免疫学分会临床微生物学组, 中国医疗保健国际交流促进会临床微生物与感染分会. 宏基因组高通量测序技术应用于感染性疾病病原检测中国专家共识. 中华检验医学杂志, 2021, 44(2): 107-120.
18. 叶福强, 李鹏, 韩一芳, 等. 基于纳米孔测序技术的呼吸道病原体快速确认. 分子诊断与治疗杂志, 2020, 12(2): 127-132, 150.
19. 李丽, 金力, 朱咏臻, 等. 2014-2019 年某医院血流感染患者的临床特征和病原学分析. 中国抗生素杂志, 2022, 47(1): 84-89.
20. Wang K, Li P, Lin Y, et al. Metagenomic diagnosis for a culture-negative sample from a patient with severe pneumonia by nanopore and next-generation sequencing. Front Cell Infect Microbiol, 2020, 10: 182.
21. Charalampous T, Kay GL, Richardson H, et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol, 2019, 37(7): 783-792.

West China Medical Journal

Application of nanopore sequencing in bloodstream infection

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