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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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, 劉淑梅, 等. 首都醫科大學附屬復興醫院 2012 年住院患者血流感染分析. 中華內科雜志, 2016, 55(8): 609-612.
6.	張家源, 陳玉梅, 鄒堯, 等. 重癥血液病患兒血流感染的臨床分析. 中華醫院感染學雜志, 2014(20): 5136-5138.
7.	郭鷹, 江代紅, 郭富饒. 血流感染的實驗室診斷技術進展. 實用醫學雜志, 2021, 37(17): 2300-2303.
8.	劉曄, 許小毛. 基于納米孔測序技術的臨床檢測研究進展. 中華檢驗醫學雜志, 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, ?svold 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.	范帥華, 杜鵬程, 郭軍. 納米孔測序技術在呼吸系統感染病原學診斷中的應用價值與展望. 中華醫學雜志, 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.	王玉靜, 陸梓涔, 陳俊煜, 等. 高通量測序技術的發展及其在臨床檢測中的應用. 廈門大學學報(自然科學版), 2021, 60(5): 811-820.
17.	中華醫學會檢驗醫學分會臨床微生物學組, 中華醫學會微生物學與免疫學分會臨床微生物學組, 中國醫療保健國際交流促進會臨床微生物與感染分會. 宏基因組高通量測序技術應用于感染性疾病病原檢測中國專家共識. 中華檢驗醫學雜志, 2021, 44(2): 107-120.
18.	葉福強, 李鵬, 韓一芳, 等. 基于納米孔測序技術的呼吸道病原體快速確認. 分子診斷與治療雜志, 2020, 12(2): 127-132, 150.
19.	李麗, 金力, 朱詠臻, 等. 2014-2019 年某醫院血流感染患者的臨床特征和病原學分析. 中國抗生素雜志, 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, 劉淑梅, 等. 首都醫科大學附屬復興醫院 2012 年住院患者血流感染分析. 中華內科雜志, 2016, 55(8): 609-612.
6. 張家源, 陳玉梅, 鄒堯, 等. 重癥血液病患兒血流感染的臨床分析. 中華醫院感染學雜志, 2014(20): 5136-5138.
7. 郭鷹, 江代紅, 郭富饒. 血流感染的實驗室診斷技術進展. 實用醫學雜志, 2021, 37(17): 2300-2303.
8. 劉曄, 許小毛. 基于納米孔測序技術的臨床檢測研究進展. 中華檢驗醫學雜志, 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, ?svold 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. 范帥華, 杜鵬程, 郭軍. 納米孔測序技術在呼吸系統感染病原學診斷中的應用價值與展望. 中華醫學雜志, 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. 王玉靜, 陸梓涔, 陳俊煜, 等. 高通量測序技術的發展及其在臨床檢測中的應用. 廈門大學學報(自然科學版), 2021, 60(5): 811-820.
17. 中華醫學會檢驗醫學分會臨床微生物學組, 中華醫學會微生物學與免疫學分會臨床微生物學組, 中國醫療保健國際交流促進會臨床微生物與感染分會. 宏基因組高通量測序技術應用于感染性疾病病原檢測中國專家共識. 中華檢驗醫學雜志, 2021, 44(2): 107-120.
18. 葉福強, 李鵬, 韓一芳, 等. 基于納米孔測序技術的呼吸道病原體快速確認. 分子診斷與治療雜志, 2020, 12(2): 127-132, 150.
19. 李麗, 金力, 朱詠臻, 等. 2014-2019 年某醫院血流感染患者的臨床特征和病原學分析. 中國抗生素雜志, 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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