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The SEP-SEQ Trial - Clinical Validation of the Karius Plasma Next-Generation Sequencing Test for Pathogen Detection in Sepsis
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A2789 - The SEP-SEQ Trial - Clinical Validation of the Karius Plasma Next-Generation Sequencing Test for Pathogen Detection in Sepsis
Author Block: S. Thair1, R. Aquino2, H. Seng2, D. Hollman2, D. Hong2, T. A. Blauwkamp2, M. Kertesz2, C. Ho1, R. Mann1, J. Quinn1, S. Yang1; 1Emergency Medicine, Stanford, Stanford, CA, United States, 2Karius, Inc., Redwood City, CA, United States.
Rationale: Sepsis is a leading cause of death and can be caused by a wide range of potential pathogens. In up to 40% of cases, a causative pathogen is never identified. There is a need for improved diagnostic tests that can accurately identify the breadth of potential pathogens to inform effective antimicrobial therapy. Methods: We enrolled a prospective cohort of patients presenting to the hospital with signs and symptoms of sepsis. Plasma samples were collected for NGS testing at the time of initial blood culture. Cell-free DNA extracted from plasma was sequenced, human sequences removed and remaining reads aligned against a pathogen database consisting of viruses, bacteria, and eukaryotic pathogens. Relative abundance was estimated; pathogens present at high statistical significance were identified. NGS results were compared to a composite reference standard of all microbiology testing performed within 7 days of admission and clinical diagnosis as adjudicated by three independent infectious disease physicians. Results: Of 350 patients enrolled, plasma NGS identified potential pathogens in 60% (210/350) of septic subjects including DNA viruses, bacteria (including fastidious/unculturable bacteria such as Mycobacterium tuberculosis), and fungi. In contrast, 18% (63/350) subjects had a positive initial blood culture and 37.7% (132/350) had a potential infectious etiology identified using a composite microbiology laboratory standard. The NGS plasma assay had a positive agreement of 84.1% (53/63) compared to initial blood culture (after excluding contaminants). After clinical adjudication, 86.2% (181/210) of the positive plasma NGS results were deemed to be consistent with the septic event. Conclusions: With a single blood draw, the Karius plasma NGS assay identified a broad range of pathogens in septic patients almost three times more often than blood culture and more often than all microbiology tests combined. This plasma NGS test can identify viruses, bacteria, and eukaryotic pathogens which can provide valuable information to help clinicians better target antimicrobial therapy for patients with sepsis.
Author Block: S. Thair1, R. Aquino2, H. Seng2, D. Hollman2, D. Hong2, T. A. Blauwkamp2, M. Kertesz2, C. Ho1, R. Mann1, J. Quinn1, S. Yang1; 1Emergency Medicine, Stanford, Stanford, CA, United States, 2Karius, Inc., Redwood City, CA, United States.
Rationale: Sepsis is a leading cause of death and can be caused by a wide range of potential pathogens. In up to 40% of cases, a causative pathogen is never identified. There is a need for improved diagnostic tests that can accurately identify the breadth of potential pathogens to inform effective antimicrobial therapy. Methods: We enrolled a prospective cohort of patients presenting to the hospital with signs and symptoms of sepsis. Plasma samples were collected for NGS testing at the time of initial blood culture. Cell-free DNA extracted from plasma was sequenced, human sequences removed and remaining reads aligned against a pathogen database consisting of viruses, bacteria, and eukaryotic pathogens. Relative abundance was estimated; pathogens present at high statistical significance were identified. NGS results were compared to a composite reference standard of all microbiology testing performed within 7 days of admission and clinical diagnosis as adjudicated by three independent infectious disease physicians. Results: Of 350 patients enrolled, plasma NGS identified potential pathogens in 60% (210/350) of septic subjects including DNA viruses, bacteria (including fastidious/unculturable bacteria such as Mycobacterium tuberculosis), and fungi. In contrast, 18% (63/350) subjects had a positive initial blood culture and 37.7% (132/350) had a potential infectious etiology identified using a composite microbiology laboratory standard. The NGS plasma assay had a positive agreement of 84.1% (53/63) compared to initial blood culture (after excluding contaminants). After clinical adjudication, 86.2% (181/210) of the positive plasma NGS results were deemed to be consistent with the septic event. Conclusions: With a single blood draw, the Karius plasma NGS assay identified a broad range of pathogens in septic patients almost three times more often than blood culture and more often than all microbiology tests combined. This plasma NGS test can identify viruses, bacteria, and eukaryotic pathogens which can provide valuable information to help clinicians better target antimicrobial therapy for patients with sepsis.
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