Next-generation sequencing of microbial cell-free DNA for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts

Abstract

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.  Methods: Here we report our experience 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: Among five hematological malignancy patients, for whom a microbiological diagnosis was established, pathogen identification by cfDNA NGS demonstrated 100% positive agreement with conventional diagnostic laboratory methods. Further, cfDNA identified the etiological agent in two patients with culture negative sepsis who had undergone hematopoietic stem cell transplant. Conclusion: These data 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.