P-2113. Performance of a Commercial Metagenomic Microbial Cell-free DNA Sequencing Assay in Identifying Explanatory Pathogens of Pulmonary Nodules in a Multi-Center Pediatric Immunocompromised Population
Craig Boge, Brian T Fisher, Anna R Huppler, Sarah K Johnson, Sydney Shuster, Subhiksha Karthikeyan, Morgan Zalot, Yeh-Chung Chang, Paul Sue, Natalie J Dailey Garnes, Catherine Aftandilian, Gabriela Maron, Tamara P Miller, Inci Yildirim, Lillian Sung, Lara A Danziger-Isakov

TL;DR
A commercial metagenomic DNA sequencing test was evaluated for identifying pathogens causing lung nodules in immunocompromised children, showing moderate accuracy but not sufficient to replace traditional methods.
Contribution
This study evaluates the diagnostic performance of a commercial metagenomic cell-free DNA assay in immunocompromised pediatric patients with pulmonary nodules.
Findings
The mcfDNA assay had a sensitivity of 44.8% and specificity of 77.2% for identifying explanatory pathogens.
18 cases had pathogens detected by mcfDNA that were missed by traditional methods.
The assay's low negative predictive value limits its use for ruling out infection.
Abstract
Pulmonary nodules on radiography in setting of recent neutropenia or immune suppression for graft versus host disease (GVHD) are concerning for bacterial or invasive fungal disease (IFD). Determining etiology often requires invasive tests that may be inconclusive and pose risk. Non-invasive assays that detect pathogens may improve time to optimal therapy and outcomes. This study sought to evaluate the utility of a commercial metagenomic microbial cell-free DNA (mcfDNA) sequencing assay (Karius SpectrumTM) to identify causative pathogens in this setting. Subjects aged 120 days to 22 years with recent neutropenia or GVHD and with newly detected chest imaging findings meeting EORTC/MSGERC guidelines for possible IFD were enrolled at 27 North American hospitals from 2019 to 2024. Plasma was collected ≤144 hours after imaging and shipped frozen for mcfDNA testing by Karius Laboratories.…
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Taxonomy
TopicsNeutropenia and Cancer Infections · Lung Cancer Research Studies · Antifungal resistance and susceptibility
