Diagnostic efficiency of metagenomic next-generation sequencing for suspected infection in allogeneic hematopoietic stem cell transplantation recipients.

Jiayu Huang, Yeqian Zhao, Chuanhe Jiang, Dongsheng Han, Zengkai Pan, Zilu Zhang, Luxiang Wang, Wei Chen, Su Li, Yanmin Zhao, Xiaoxia Hu
Author Information
  1. Jiayu Huang: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  2. Yeqian Zhao: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  3. Chuanhe Jiang: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  4. Dongsheng Han: Centre of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  5. Zengkai Pan: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  6. Zilu Zhang: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  7. Luxiang Wang: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  8. Wei Chen: Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  9. Su Li: GoBroad Medical Institute of Hematology (Shanghai Center), Liquan Hospital, Shanghai, China.
  10. Yanmin Zhao: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  11. Xiaoxia Hu: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Introduction: Immunosuppression predisposes allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients to infection. Prompt and accurate identification of pathogens is crucial to optimize treatment strategies. This multi-center retrospective study aimed to assess the ability of metagenomic next-generation sequencing (mNGS) to detect causative pathogens in febrile allo-HSCT recipients and examined its concordance with conventional microbiological tests (CMT).
Methods: We performed mNGS and CMT on samples obtained from 153 patients with suspected infection during allo-HSCT. Patients were grouped based on their neutropenic status at the time of sampling.
Results: The mNGS test was more sensitive than CMT (81.1% vs. 53.6%, <0.001) for diagnosing clinically suspected infection, especially in the non-neutropenia cohort. mNGS could detect fungi and viruses better than bacteria, with a higher sensitivity than CMT. Immune events were diagnosed in 57.4% (35/61) of the febrile events with negative mNGS results, and 33.5% (48/143) with negative CMT results (=0.002). The treatment success rate of the targeted anti-infection strategy was significantly higher when based on mNGS than on empirical antibiotics (85% vs. 56.5%, =0.004).
Conclusion: The mNGS test is superior to CMT for identifying clinically relevant pathogens, and provides valuable information for anti-infection strategies in allo-HSCT recipients. Additionally, attention should be paid to immune events in patients with negative mNGS results.

Keywords

References

  1. Front Cell Infect Microbiol. 2022 Mar 22;12:862526 [PMID: 35392613]
  2. J Antimicrob Chemother. 2018 Dec 1;73(12):3221-3230 [PMID: 30085172]
  3. Med Microbiol Immunol. 2020 Feb;209(1):15-21 [PMID: 31478067]
  4. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S231-S240 [PMID: 30423048]
  5. Clin Infect Dis. 2017 Jan 1;64(1):87-91 [PMID: 27682069]
  6. Bone Marrow Transplant. 2021 Aug;56(8):1978-1983 [PMID: 33824437]
  7. J Microbiol Immunol Infect. 2019 Dec;52(6):973-982 [PMID: 30322746]
  8. Infect Dis Clin North Am. 2019 Jun;33(2):361-380 [PMID: 31005133]
  9. J Infect Chemother. 2016 Aug;22(8):505-14 [PMID: 27344206]
  10. J Infect. 2023 Jan;86(1):14-23 [PMID: 36462587]
  11. Blood Rev. 2019 Mar;34:34-44 [PMID: 30467067]
  12. Front Microbiol. 2022 Apr 18;13:868160 [PMID: 35509305]
  13. Blood Rev. 2021 Jul;48:100792 [PMID: 33386151]
  14. Infect Drug Resist. 2020 Feb 19;13:567-576 [PMID: 32110067]
  15. BMC Infect Dis. 2018 Apr 2;18(1):155 [PMID: 29609553]
  16. BMC Infect Dis. 2021 Jan 13;21(1):62 [PMID: 33435894]
  17. N Engl J Med. 2017 Nov 30;377(22):2167-2179 [PMID: 29171820]
  18. Lancet. 2020 Feb 22;395(10224):565-574 [PMID: 32007145]
  19. Curr Res Transl Med. 2019 May;67(2):51-55 [PMID: 30683577]
  20. J Hematol Oncol. 2020 Mar 30;13(1):27 [PMID: 32228710]
  21. Haematologica. 2021 Jul 01;106(7):1794-1804 [PMID: 33730842]
  22. J Antimicrob Chemother. 2016 Sep;71(9):2405-13 [PMID: 27550993]
  23. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S174-S178 [PMID: 30423039]
  24. Clin Infect Dis. 2020 Dec 3;71(9):2365-2374 [PMID: 32076709]
  25. Lancet Infect Dis. 2019 Aug;19(8):e260-e272 [PMID: 31153807]
  26. Microbiome. 2021 Jan 24;9(1):28 [PMID: 33487167]
  27. Ann Transl Med. 2020 Mar;8(5):227 [PMID: 32309374]
  28. Front Cell Infect Microbiol. 2022 Jan 07;11:805514 [PMID: 35071052]
  29. Ann Hematol. 2022 Mar;101(3):491-511 [PMID: 34994811]
  30. Bone Marrow Transplant. 2018 Feb;53(2):129-137 [PMID: 28967899]
  31. Chest. 2007 Apr;131(4):1173-80 [PMID: 17426225]
  32. Am J Respir Crit Care Med. 2017 Dec 15;196(12):1610-1612 [PMID: 28475350]

MeSH Term

Humans
Retrospective Studies
High-Throughput Nucleotide Sequencing
Anti-Bacterial Agents
Hematopoietic Stem Cell Transplantation
Immunosuppression Therapy
Metagenomics
Sensitivity and Specificity

Chemicals

Anti-Bacterial Agents

Word Cloud

Created with Highcharts 10.0.0mNGSCMTinfectionallo-HSCTrecipientseventspathogensmetagenomicnext-generationsequencingsuspectednegativeresultsallogeneichematopoieticstemcelltransplantationtreatmentstrategiesdetectfebrileconventionalmicrobiologicaltestspatientsbasedtestvsclinicallyhigher5%=0anti-infectionimmuneefficiencyIntroduction:ImmunosuppressionpredisposesPromptaccurateidentificationcrucialoptimizemulti-centerretrospectivestudyaimedassessabilitycausativeexaminedconcordanceMethods:performedsamplesobtained153PatientsgroupedneutropenicstatustimesamplingResults:sensitive811%536%<0001diagnosingespeciallynon-neutropeniacohortfungivirusesbetterbacteriasensitivityImmunediagnosed574%35/613348/143002successratetargetedstrategysignificantlyempiricalantibiotics85%56004Conclusion:superioridentifyingrelevantprovidesvaluableinformationAdditionallyattentionpaidDiagnosticclinicaldiagnostic

Similar Articles

Cited By