Clinical Metagenomic Sequencing for Pathogen Detection: When to Test and How to Interpret
This Clinical Chemistry review critically evaluates direct-from-specimen metagenomic NGS across cerebrospinal fluid, plasma, and respiratory specimens, finding early promise in meningitis, invasive fungal infections, and community-acquired pneumonia. However, the proportion of cases with positive clinical impact remains low and costs are high, underscoring the need for better patient selection criteria. The authors provide early testing recommendations and highlight barriers to routine laboratory implementation.
The original study
Navigating Clinical Utilization of Direct-from-Specimen Metagenomic Pathogen Detection: Clinical Applications, Limitations, and Testing Recommendations.
- Authors
- Filkins LM, Bryson AL, Miller SA, Mitchell SL
- Journal
- Clinical chemistry
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 33141913
Original abstract
BACKGROUND: Metagenomic next generation sequencing (mNGS) is becoming increasingly available for pathogen detection directly from clinical specimens. These tests use target-independent, shotgun sequencing to detect potentially unlimited organisms. The promise of this methodology to aid infection diagnosis is demonstrated through early case reports and clinical studies. However, the optimal role of mNGS in clinical microbiology remains uncertain. CONTENT: We reviewed studies reporting clinical use of mNGS for pathogen detection from various specimen types, including cerebrospinal fluid, plasma, lower respiratory specimens, and others. Published clinical study data were critically evaluated and summarized to identify promising clinical indications for mNGS-based testing, to assess the clinical impact of mNGS for each indication, and to recognize test limitations. Based on these clinical studies, early testing recommendations are made to guide clinical utilization of mNGS for pathogen detection. Finally, current barriers to routine clinical laboratory implementation of mNGS tests are highlighted. SUMMARY: The promise of direct-from-specimen mNGS to enable challenging infection diagnoses has been demonstrated through early clinical studies of patients with meningitis or encephalitis, invasive fungal infections, community acquired pneumonia, and other clinical indications. However, the proportion of patient cases with positive clinical impact due to mNGS testing is low in published studies and the cost of testing is high, emphasizing the importance of improving our understanding of 'when to test' and for which patients mNGS testing is appropriate.