Next-generation sequencing of microbial cell-free DNA for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts.
| Autor: | Camargo JF; Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Ahmed AA; Karius, Inc., Redwood City, CA, USA., Lindner MS; Karius, Inc., Redwood City, CA, USA., Morris MI; Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Anjan S; Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Anderson AD; Department of Pharmacy, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, 33136, USA., Prado CE; Department of Microbiology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Dalai SC; Karius, Inc., Redwood City, CA, USA., Martinez OV; Department of Microbiology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Komanduri KV; Division of Hematology Oncology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. |
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| Jazyk: | angličtina |
| Zdroj: | F1000Research [F1000Res] 2019 Jul 26; Vol. 8, pp. 1194. Date of Electronic Publication: 2019 Jul 26 (Print Publication: 2019). |
| DOI: | 10.12688/f1000research.19766.3 |
| Abstrakt: | Background: Cell-free DNA (cfDNA) sequencing has emerged as an effective laboratory method for rapid and noninvasive diagnosis in prenatal screening testing, organ transplant rejection screening, and oncology liquid biopsies but clinical experience for use of this technology in diagnostic evaluation of infections in immunocompromised hosts is limited. Methods: We conducted an exploratory study using next-generation sequencing (NGS) for detection of microbial cfDNA in a cohort of ten immunocompromised patients with febrile neutropenia, pneumonia or intra-abdominal infection. Results: Pathogen identification by cfDNA NGS demonstrated positive agreement with conventional diagnostic laboratory methods in 7 (70%) cases, including patients with proven/probable invasive aspergillosis, Pneumocystis jirovecii pneumonia, Stenotrophomonas maltophilia bacteremia, Cytomegalovirus and Adenovirus viremia. NGS results were discordant in 3 (30%) cases including two patients with culture negative sepsis who had undergone hematopoietic stem cell transplant in whom cfDNA testing identified the etiological agent of sepsis; and one kidney transplant recipient with invasive aspergillosis who had received >6 months of antifungal therapy prior to NGS testing. Conclusion: These observations support the clinical utility of measurement of microbial cfDNA sequencing from peripheral blood for rapid noninvasive diagnosis of infections in immunocompromised hosts. Larger studies are needed. Competing Interests: Competing interests: Karius, Inc. ran the tests on the clinical specimens for these 10 patients at no charge to our institution. (Copyright: © 2019 Camargo JF et al.) |
| Databáze: | MEDLINE |
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