{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:16:12Z","timestamp":1793304972787,"version":"4.5.0"},"reference-count":15,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32AI007036-43"],"award-info":[{"award-number":["5T32AI007036-43"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: The Karius Test (KT), a microbial cell-free DNA next-generation sequencing assay, is increasingly utilized in challenging infectious syndromes. However, its real-world clinical utility and cost-effectiveness remain uncertain. Methods: We conducted a retrospective review of 88 KT results from adult patients at UC San Diego Health between July 2017 and April 2024. Each case was evaluated for clinical impact using standardized criteria. We analyzed diagnostic yield, turnaround time, number needed to test (NNT), and institutional billing data for reimbursement and cost implications. Results: Of 88 unique tests, forty-nine (55.7%) identified at least one pathogen. Eleven (12.5%) had a positive clinical impact\u2014eight provided the only microbiologic diagnosis, and three were faster than conventional methods. Vascular\/graft infections showed the highest yield. Twenty-one tests had a neutral impact; fifty-six showed no clinical benefit. The Median turnaround time was 3 days. The NNT was 6.1 or 2.75 including neutral cases. Cost analysis revealed a substantial financial burden without transparent reimbursement mechanisms in inpatient settings. Conclusion: The KT demonstrates modest clinical utility with noteworthy benefits in select scenarios. Given its high cost and variable impact, we advocate for diagnostic stewardship led by infectious disease specialists to optimize test use and minimize unnecessary expense.<\/jats:p>","DOI":"10.3390\/pathogens14080811","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T16:09:55Z","timestamp":1755274195000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Cell-Free DNA Plasma Next-Generation Sequencing Test\u2014Is It Worth the Cost?"],"prefix":"10.3390","volume":"14","author":[{"given":"Sean","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Infection Prevention and Clinical Epidemiology and Antimicrobial Stewardship Programs, University of California San Diego Health, San Diego, CA 92103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-8589","authenticated-orcid":false,"given":"Francesca","family":"Torriani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Infection Prevention and Clinical Epidemiology and Antimicrobial Stewardship Programs, University of California San Diego Health, San Diego, CA 92103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-2019","authenticated-orcid":false,"given":"Shira","family":"Abeles","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Infection Prevention and Clinical Epidemiology and Antimicrobial Stewardship Programs, University of California San Diego Health, San Diego, CA 92103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahnika","family":"Kline","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Pathology, Center for Advanced Laboratory Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","unstructured":"(2011). Microbiology by numbers. Nat. Rev. Microbiol., 9."},{"key":"ref_2","unstructured":"Santo, L., and Kang, K. (2025, July 14). National Hospital Ambulatory Medical Care Survey: 2019 National Summary Tables, Available online: https:\/\/stacks.cdc.gov\/view\/cdc\/123251."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev-pathmechdis-012418-012751","article-title":"Clinical metagenomic next-generation sequencing for pathogen detection","volume":"14","author":"Gu","year":"2019","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e178003","DOI":"10.1172\/JCI178003","article-title":"Status check: Next-generation sequencing for infectious-disease diagnostics","volume":"134","author":"Rodino","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ijantimicag.2007.06.024","article-title":"Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria","volume":"30","author":"Fenollar","year":"2007","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1128\/CMR.00043-09","article-title":"The era of molecular and other non-culture-based methods in diagnosis of sepsis","volume":"23","author":"Mancini","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1056\/NEJMra064928","article-title":"Infection in solid-organ transplant recipients","volume":"357","author":"Fishman","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_8","unstructured":"(2025, March 23). Clinical Data. Karius. Available online: https:\/\/kariusdx.com\/clinical-evidence\/clinical-data."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41564-018-0349-6","article-title":"Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease","volume":"4","author":"Blauwkamp","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.clinmicnews.2021.04.003","article-title":"The next big thing? next-generation sequencing of microbial cell-free DNA using the Karius Test","volume":"43","author":"Morales","year":"2021","journal-title":"Clin. Microbiol. Newsl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S432","DOI":"10.1093\/ofid\/ofab466.858","article-title":"661. clinical utility and impact of the metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decision: A Single-Center Retrospective Study","volume":"8","author":"Noe","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S437","DOI":"10.1093\/ofid\/ofab466.866","article-title":"669. metagenomic plasma microbial cell free DNA-sequencing assists in diagnosis of infections and critical antimicrobial changes in immunocompromised hosts","volume":"8","author":"Vissichelli","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Aiden-Croix Thompson, R., Donnelley, M.A., Trigg, K., Fan, S., Wilson, M.D., Cohen, S.H., Thompson, G.R., and Desai, A.N. (2024). Utility of Microbial Cell Free DNA Next-Generation Sequencing for Diagnosis and Management of Infectious Diseases: A Retrospective Cohort Study. Diagn. Microbiol. Infect. Dis., 110.","DOI":"10.2139\/ssrn.4689645"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/cid\/ciaa035","article-title":"Clinical impact of metagenomic next-generation sequencing of plasma cell-free DNA for the diagnosis of infectious diseases: A multicenter retrospective cohort study","volume":"72","author":"Hogan","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shishido, A.A., Noe, M., Saharia, K., and Luethy, P. (2022). Clinical impact of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decisions: A single-center retrospective study. BMC Infect. 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