Clinical Utility and Impact of the Metagenomic Microbial Plasma Cell-Free DNA Next-Generation Sequencing Assay on Treatment Decision: A Single-Center Retrospective Study

Abstract

Background Metagenomic next-generation sequencing (mNGS) of microbial cell-free DNA (mcfDNA) allows for non-invasive pathogen detection from plasma. However, there is little data describing the optimal role for this assay in real-world clinical decision making. Methods We performed a single-center retrospective cohort study of adult patients for whom a mcfDNA test was sent between May 2019 and February 2021. Clinical impact was arbitrated after review and discussion of each case. Results A total of 80 patients were included. The most common reason for sending the assay was unknown microbiologic diagnosis (78%), followed by avoiding invasive procedures (14%). The test had a positive impact in 34 (43%), a negative impact in 2 (3%), and uncertain or no impact in 44 (55%). A positive impact was observed in solid organ transplant recipients (SOTR, 71.4%, p=0.003), sepsis (71.4%, p=0.003), and those receiving antimicrobial agents for less than 7 days prior to mcfDNA testing (i.e., 61.8%, p=0.004). Conclusion Clinical utility of mcfDNA testing was highest in SOTR and patients with sepsis. Prolonged antimicrobial use prior to mcfDNA testing limited the utility of the assay. Prospective studies evaluating the utility of mcfDNA assays should be performed to further clarify its role in clinical management.

Problems with etiologic diagnosis of community-acquired pneumonia using plasma microbial cell-free DNA sequencing

“…In the absence of a microbiologic diagnosis, it is difficult to be certain whether identification of bacterial DNA in plasma represents a true or false positive. 3,4 In our small cohort of nonbacteremic patients with CAP, clear microbiologic diagnoses were established in every case with discordance between QB and KT in the majority of cases. If the finding, in sputum, of large numbers of typical respiratory pathogens by Gram stain and QB is correct, KT was falsely negative in two cases.…”