Clinical metagenomic sequencing of plasma microbial cell-free DNA for febrile neutropenia in patients with acute leukaemia

被引:22
作者
Feng, Sizhou [1 ]
Rao, Guanhua [2 ]
Wei, Xudong [3 ,4 ]
Fu, Rong [5 ]
Hou, Ming [6 ]
Song, Yongping [3 ,4 ]
Xu, Chunhui [1 ]
Han, Peng [2 ]
Gong, Benfa [1 ]
Chen, Xin [1 ]
Wang, Yihao [5 ]
Dong, Xiaoyuan [6 ]
Jiang, Zhi [2 ]
Wang, Jianxiang [1 ,7 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, Haihe Lab Cell Ecosyst,State Key Lab Expt Hematol, Tianjin, Peoples R China
[2] Genskey Med Technol Co Ltd, Dept Med, Beijing, Peoples R China
[3] Zhengzhou Univ, Affiliated Canc Hosp, Dept Hematol, Zhengzhou, Peoples R China
[4] Henan Canc Hosp, Zhengzhou, Peoples R China
[5] Tianjin Med Univ, Gen Hosp, Dept Hematol, Tianjin, Peoples R China
[6] Shandong Univ, Qilu Hosp, Dept Hematol, Shandong Prov Key Lab Immunohematol, Jinan, Peoples R China
[7] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China
关键词
Febrile neutropenia; Infection; Metagenomic sequencing; Pathogen diagnosis; Plasma microbial cell -free DNA; DIAGNOSIS;
D O I
10.1016/j.cmi.2023.05.034
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: To evaluate the diagnostic performance and clinical impact of metagenomic next-generation sequencing (mNGS) of plasma microbial cell-free DNA (mcfDNA) in febrile neutropenia (FN). Methods: In a 1-year, multicentre, prospective study, we enrolled 442 adult patients with acute leukaemia with FN and investigated the usefulness of mNGS of plasma mcfDNA for identification of infectious pathogens. The results of mNGS were available to clinicians in real time. The performance of mNGS testing was evaluated in comparison with blood culture (BC) and a composite standard that incorporated standard microbiological testing and clinical adjudication. Results: In comparison with BC, the positive and negative agreements of mNGS were 81.91% (77 of 94) and 60.92% (212 of 348), respectively. By clinical adjudication, mNGS results were categorized by infectious diseases specialists as definite (n = 76), probable (n = 116), possible (n = 26), unlikely (n = 7), and false negative (n = 5). In 225 mNGS-positive cases, 81 patients (36%) underwent antimicrobials adjustment, resulting in positive impact on 79 patients and negative impact on two patients (antibiotics overuse). Further analysis indicated that mNGS was less affected by prior antibiotics exposure than BC. Discussion: Our results indicate that mNGS of plasma mcfDNA increased the detection of clinically significant pathogens and enabled early optimization of antimicrobial therapy in patients with acute leukaemia with FN. Sizhou Feng, Clin Microbiol Infect 2024;30:107 (c) 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:107 / 113
页数:7
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