For five years, there has been steadily rising interest in clinical applications of pathogen metagenomics - tests that assay 100's of pathogens concurrently using NGS.
The topic is featured in the July 2025 CAP TODAY, and includes a trackback to an April 2025 webinar that is available to stream.
Find the article by Sherrie Rice here:
https://www.captodayonline.com/for-infectious-disease-plasma-microbial-cf-dna-testing/
Find the webinar here:
AI CORNER
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Here’s a high-level professional summary of the uploaded CAP TODAY article (April 2025 issue) titled “Metagenomic sequencing comes into its own in clinical practice” by Sherrie Rice focusing on the use of plasma microbial cfDNA (mcfDNA) testing and spotlighting a large Bay Area referene lab, Karius.
Summary for Lab Directors and Clinical Stakeholders:
The CAP TODAY feature highlights the increasing clinical integration of metagenomic sequencing, particularly through microbial cell-free DNA (mcfDNA) plasma testing. It centers on the Karius Test, a leading platform that identifies over 1,000 pathogens—including bacteria, viruses, fungi, and parasites—via next-generation sequencing (NGS) of cfDNA extracted from a standard blood draw.
Key Highlights:
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Clinical Utility: The article provides compelling examples of how the Karius Test delivers actionable insights in difficult diagnostic cases. Dr. David Hong (UCLA) and Dr. John Perfect (Duke) underscore its value for deep-seated infections, atypical pathogens, and immunocompromised patients, where traditional culture and PCR often fall short.
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Real-World Cases: Cases cited include diagnosis of Nocardia, Aspergillus, and rare pathogens in febrile neutropenia or post-transplant settings. The speed and breadth of detection are particularly beneficial in patients with nonspecific symptoms or sterile-site infections.
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Diagnostic Algorithm Integration: Institutions such as UCLA and Duke are working toward formally integrating mcfDNA testing into clinical pathways, often after initial workups are inconclusive. There is growing emphasis on defining test indications and determining the optimal point in the diagnostic timeline.
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Challenges & Opportunities: The article doesn’t ignore hurdles—test interpretation can be nuanced (especially with colonizing organisms), and reimbursement remains a moving target. Yet consensus is growing that metagenomic cfDNA adds significant value when used judiciously in the right populations.
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Future Direction: Karius is expanding its clinical utility data and engaging in studies to support broader adoption. The article implies that metagenomic plasma testing is moving from "boutique" to mainstream, with increasing institutional support.
Takeaway:
This is a balanced yet positive appraisal of the Karius Test and mcfDNA metagenomics more broadly. For lab directors and clinicians tracking advanced diagnostics, it reflects a pivotal moment in infectious disease testing—where plasma-based metagenomics is shedding its novelty and becoming a serious clinical tool. The article serves as a call to evaluate how, when, and where your institution may integrate such technologies into standard care, particularly for complex or immunocompromised cases.
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Webinar AI Summary from Auto Transcript
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Certainly — here’s the same detailed content as bullet points, suitable for pasting into HTML or text format:
Summary of CAP TODAY Webinar: “Harnessing the Power of Microbial Cell-Free DNA” (April 22, 2025)
Featuring Karius and OSF Healthcare
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Webinar Overview
CAP TODAY hosted a webinar exploring the use of microbial cell-free DNA (mcfDNA) testing via metagenomic sequencing, focusing on the Karius Test and its implementation at OSF Healthcare. -
Technology Introduction (Dr. Tim Blauwkamp, Karius)
Dr. Blauwkamp presented the core technology: sequencing microbial cfDNA in plasma to detect pathogens without culture. Karius developed proprietary methods to reduce noise (e.g., contamination) and accurately quantify pathogen DNA, treating infection diagnostics as a form of "liquid biopsy." -
Clinical Implementation (Dr. John Ferrell, OSF Healthcare)
Dr. Ferrell described OSF’s structured approach to integrating the Karius test. The test is embedded in EPIC and restricted to ID providers. They average ~5 tests/week, and two-thirds return actionable positives. The test has proven valuable for diagnosing infections in patients with AIDS, cancer, or FUO. -
Case Highlights
Clinical cases showed how Karius testing detected Toxoplasma gondii, Mycobacterium abscessus, Histoplasma, and Pneumocystis jirovecii—often earlier and more definitively than cultures or imaging. The test frequently avoided invasive procedures like bronchoscopy. -
Turnaround Time & Operations
97% of results are returned within 24 hours of lab receipt. The workflow includes overnight sequencing and automated analysis. Reports list only significant findings, with quantitative values and optional resistance marker follow-ups. -
Stewardship & EMR Integration
OSF uses built-in EMR prompts to prevent duplicate blood cultures or inappropriate orders. Only ID physicians can order the Karius test, supporting strong stewardship and efficient resource use. -
Economic Impacts
By avoiding invasive diagnostics and reducing hospital stays, OSF sees significant savings. As Dr. Ferrell put it: “If I can diagnose and discharge a patient faster, someone else can use that bed.” This aligns with value-based care and system-wide efficiency goals. -
Literature Support
Over 200 publications support Karius, including Mayo Clinic’s 2025 study on Fever of Unknown Origin (FUO). In that cohort, Karius was the sole diagnostic tool identifying infection in 15 of 69 patients—roughly one-third of infectious FUO cases. -
Takeaway Message
Metagenomic mcfDNA testing is no longer niche—it’s a practical, impactful clinical tool for identifying pathogens when conventional methods fail. Thoughtful integration and stewardship remain essential to its success and sustainability.
Let me know if you'd like a version with HTML tags added.
