The diagnostic and clinical utility of microbial cell-free DNA sequencing in a real-world setting

Zoe Freeman Weiss; Alexander D Pyden; Tulip A Jhaveri; Sanjat Kanjilal

doi:10.1016/j.diagmicrobio.2023.116004

The diagnostic and clinical utility of microbial cell-free DNA sequencing in a real-world setting

Diagn Microbiol Infect Dis. 2023 Oct;107(2):116004. doi: 10.1016/j.diagmicrobio.2023.116004. Epub 2023 Jun 15.

Authors

Zoe Freeman Weiss¹, Alexander D Pyden², Tulip A Jhaveri³, Sanjat Kanjilal⁴

Affiliations

¹ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Division of Infectious Diseases and Geographic Medicine and Department of Anatomic and Clinical Pathology, Tufts University School of Medicine, Boston, MA, USA. Electronic address: zoefreemanweiss@gmail.com.
² Department of Laboratory Medicine, Lahey Hospital and Medical Center, Burlington, MA, USA.
³ Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, USA.
⁴ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Harvard Pilgrim Healthcare Institute & Harvard Medical School, Department of Population Medicine; Boston, MA, USA.

PMID: 37467522
DOI: 10.1016/j.diagmicrobio.2023.116004

Abstract

Microbial cell free DNA sequencing is increasingly used for diagnosis of infection but few studies describe its utility in real-world settings. We performed a single-center retrospective case series of microbial cell free DNA testing using the Karius assay from 29 patient samples to define the clinical reasoning and the impact of testing. Indications fell into 3 categories, identifying a causative pathogen in patients with an infectious syndrome and negative microbiologic workup (15/29, 52%), seeking another pathogen when organisms identified by traditional diagnostics failed to explain the clinical presentation (9/29, 31%) and to "rule out" infection in patients with nonspecific symptoms and negative microbiologic workup (5/29, 17%). Clinical impact was positive in 13/29 (45%) and all were for patients with high pretest probability for infection. Impact was negative in 3/29 (10%) cases. There was no impact in 15/29 (52%) cases. Further work is needed to define the optimal timing accounting for test performance, and patient characteristics.

Keywords: Culture-independent; Diagnostics; Fungal diagnostics; Metagenomic sequencing; Nonculture diagnostics.

MeSH terms

Cell-Free Nucleic Acids*
High-Throughput Nucleotide Sequencing
Humans
Metagenomics
Retrospective Studies
Sequence Analysis, DNA

Substances

Cell-Free Nucleic Acids