TY - JOUR
T1 - Next-generation sequencing of microbial cell-free dna for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts [version 3; peer review
T2 - 2 approved, 1 approved with reservations]
AU - Camargo, Jose F.
AU - Ahmed, Asim A.
AU - Lindner, Martin S.
AU - Morris, Michele I.
AU - Anjan, Shweta
AU - Anderson, Anthony D.
AU - Prado, Clara E.
AU - Dalai, Sudeb C.
AU - Martinez, Octavio V.
AU - Komanduri, Krishna V.
N1 - Funding Information:
This work was supported by Karius, Inc., Redwood City, CA.
Funding Information:
Are the conclusions drawn adequately supported by the results?
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Cell-free microbial DNA
KW - Hematopoietic stem cell transplant
KW - Immunocompromised host
KW - Infection
KW - Next generation sequencing
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U2 - 10.12688/f1000research.19766.1
DO - 10.12688/f1000research.19766.1
M3 - Article
C2 - 31814964
AN - SCOPUS:85076298255
VL - 3
JO - Wellcome Open Research
JF - Wellcome Open Research
SN - 2398-502X
M1 - 1194
ER -