{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:20:58Z","timestamp":1793254858513,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis (P &amp;lt; .001) or OAIs with concomitant presence of endocarditis or endovascular infection (P = .005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofae328","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T17:37:54Z","timestamp":1718732274000},"source":"Crossref","is-referenced-by-count":16,"title":["Plasma Microbial Cell-free DNA Next-generation Sequencing Can Be a Useful Diagnostic Tool in Patients With Osteoarticular Infections"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0125-9551","authenticated-orcid":false,"given":"Francesco","family":"Petri","sequence":"first","affiliation":[{"name":"Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester, Minnesota , USA"},{"name":"Department of Infectious Diseases, ASST Fatebenefratelli Sacco, \u201cL. Sacco\u201d University Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7896-4588","authenticated-orcid":false,"given":"Omar K","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9538-6214","authenticated-orcid":false,"given":"Nischal","family":"Ranganath","sequence":"additional","affiliation":[{"name":"Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4331-5259","authenticated-orcid":false,"given":"Said","family":"El Zein","sequence":"additional","affiliation":[{"name":"Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4955-5544","authenticated-orcid":false,"given":"Omar","family":"Abu Saleh","sequence":"additional","affiliation":[{"name":"Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie F","family":"Berbari","sequence":"additional","affiliation":[{"name":"Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3630-0668","authenticated-orcid":false,"given":"Madiha","family":"Fida","sequence":"additional","affiliation":[{"name":"Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"2024072916052064700_ofae328-B1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s41579-022-00686-0","article-title":"Skeletal infections: microbial pathogenesis, immunity and clinical management","volume":"20","author":"Masters","year":"2022","journal-title":"Nat Rev Microbiol"},{"key":"2024072916052064700_ofae328-B2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s12570-011-0056-8","article-title":"Bone and joint infections in adults: a comprehensive classification proposal","volume":"1","author":"Romano","year":"2011","journal-title":"Eur Orthop Traumatol"},{"key":"2024072916052064700_ofae328-B3","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2106\/JBJS.N.01350","article-title":"Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to 2009","volume":"97","author":"Kremers","year":"2015","journal-title":"J Bone Joint Surg Am"},{"key":"2024072916052064700_ofae328-B4","doi-asserted-by":"crossref","first-page":"254 e251","DOI":"10.1016\/j.cmi.2014.09.007","article-title":"The changing epidemiology of bacteraemic osteoarticular infections in the early 21st century","volume":"21","author":"Murillo","year":"2015","journal-title":"Clin Microbiol Infect"},{"key":"2024072916052064700_ofae328-B5","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.jbspin.2018.10.006","article-title":"Management of septic bursitis","volume":"86","author":"Lormeau","year":"2019","journal-title":"Joint Bone Spine"},{"key":"2024072916052064700_ofae328-B6","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1128\/CMR.00111-13","article-title":"Prosthetic joint infection","volume":"27","author":"Tande","year":"2014","journal-title":"Clin Microbiol Rev"},{"key":"2024072916052064700_ofae328-B7","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1136\/ard.58.4.214","article-title":"Clinical features and outcome of septic arthritis in a single UK health district 1982\u20131991","volume":"58","author":"Weston","year":"1999","journal-title":"Ann Rheum Dis"},{"key":"2024072916052064700_ofae328-B8","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1056\/NEJMcp0910753","article-title":"Clinical practice. Vertebral osteomyelitis","volume":"362","author":"Zimmerli","year":"2010","journal-title":"N Engl J Med"},{"key":"2024072916052064700_ofae328-B9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.semarthrit.2014.04.008","article-title":"Outcome of culture-negative pyogenic vertebral osteomyelitis: comparison with microbiologically confirmed pyogenic vertebral osteomyelitis","volume":"44","author":"Kim","year":"2014","journal-title":"Semin Arthritis Rheum"},{"key":"2024072916052064700_ofae328-B10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.semarthrit.2011.04.002","article-title":"Changing trends in the epidemiology of pyogenic vertebral osteomyelitis: the impact of cases with no microbiologic diagnosis","volume":"41","author":"Lora-Tamayo","year":"2011","journal-title":"Semin Arthritis Rheum"},{"key":"2024072916052064700_ofae328-B11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/BOR.0b013e3283032030","article-title":"Usefulness of broad-range PCR for the diagnosis of osteoarticular infections","volume":"20","author":"Fenollar","year":"2008","journal-title":"Curr Opin Rheumatol"},{"key":"2024072916052064700_ofae328-B12","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":"2024072916052064700_ofae328-B13","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1093\/cid\/ciab324","article-title":"Plasma microbial cell-free DNA next-generation sequencing in the diagnosis and management of febrile neutropenia","volume":"74","author":"Benamu","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2024072916052064700_ofae328-B14","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/cid\/ciad599","article-title":"Plasma microbial cell-free DNA sequencing in immunocompromised patients with pneumonia: a prospective observational study","volume":"78","author":"Bergin","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2024072916052064700_ofae328-B15","doi-asserted-by":"crossref","first-page":"e1492","DOI":"10.1093\/cid\/ciac426","article-title":"Microbial cell-free DNA identifies the causative pathogen in infective endocarditis and remains detectable Longer than conventional blood culture in patients with prior antibiotic therapy","volume":"76","author":"Eichenberger","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2024072916052064700_ofae328-B16","doi-asserted-by":"crossref","first-page":"e0062122","DOI":"10.1128\/jcm.00621-22","article-title":"Pathogen detection in infective endocarditis using targeted metagenomics on whole blood and plasma: a prospective pilot study","volume":"60","author":"Flurin","year":"2022","journal-title":"J Clin Microbiol"},{"key":"2024072916052064700_ofae328-B17","doi-asserted-by":"crossref","first-page":"e3876","DOI":"10.1093\/cid\/ciaa1639","article-title":"Liquid biopsy for invasive mold infections in hematopoietic cell transplant recipients with pneumonia through next-generation sequencing of microbial cell-free DNA in plasma","volume":"73","author":"Hill","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2024072916052064700_ofae328-B18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cmi.2021.09.039","article-title":"Culture-independent detection systems for bloodstream infection","volume":"28","author":"Peri","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"2024072916052064700_ofae328-B19","doi-asserted-by":"crossref","first-page":"e13954","DOI":"10.1111\/tid.13954","article-title":"Cell-free next-generation sequencing impacts diagnosis and antimicrobial therapy in immunocompromised hosts: a retrospective study","volume":"25","author":"Vissichelli","year":"2023","journal-title":"Transpl Infect Dis"},{"key":"2024072916052064700_ofae328-B20","doi-asserted-by":"crossref","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","article-title":"The REDCap consortium: building an international community of software platform partners","volume":"95","author":"Harris","year":"2019","journal-title":"J Biomed Inform"},{"key":"2024072916052064700_ofae328-B21","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.2106\/JBJS.20.02229","article-title":"Sequencing of circulating microbial cell-free DNA can identify pathogens in periprosthetic joint infections","volume":"103","author":"Echeverria","year":"2021","journal-title":"J Bone Joint Surg Am"},{"key":"2024072916052064700_ofae328-B22","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/jpids\/piae012","article-title":"Plasma microbial cell-free DNA sequencing for pathogen detection and quantification in children with musculoskeletal infections","volume":"13","author":"Wood","year":"2024","journal-title":"J Pediatric Infect Dis Soc"},{"key":"2024072916052064700_ofae328-B23","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.3174\/ajnr.A5337","article-title":"Yield of image-guided needle biopsy for infectious discitis: a systematic review and meta-analysis","volume":"38","author":"McNamara","year":"2017","journal-title":"AJNR Am J Neuroradiol"},{"key":"2024072916052064700_ofae328-B24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.spinee.2014.07.003","article-title":"The utility of image-guided percutaneous needle aspiration biopsy for the diagnosis of spontaneous vertebral osteomyelitis: a systematic review and meta-analysis","volume":"15","author":"Pupaibool","year":"2015","journal-title":"Spine J"},{"key":"2024072916052064700_ofae328-B25","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s10096-013-1965-y","article-title":"Microbiological diagnosis of vertebral osteomyelitis: relevance of second percutaneous biopsy following initial negative biopsy and limited yield of post-biopsy blood cultures","volume":"33","author":"Gras","year":"2014","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2024072916052064700_ofae328-B26","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s12879-022-07357-8","article-title":"Clinical impact of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decisions: a single-center retrospective study","volume":"22","author":"Shishido","year":"2022","journal-title":"BMC Infect Dis"},{"key":"2024072916052064700_ofae328-B27","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1093\/cid\/ciab742","article-title":"Microbial cell-free DNA identifies etiology of bloodstream infections, persists longer than conventional blood cultures, and its duration of detection is associated with metastatic infection in patients with Staphylococcus aureus and gram-negative bacteremia","volume":"74","author":"Eichenberger","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2024072916052064700_ofae328-B28","doi-asserted-by":"crossref","first-page":"ofad546","DOI":"10.1093\/ofid\/ofad546","article-title":"Comparison of blood-based shotgun and targeted metagenomic sequencing for microbiological diagnosis of infective endocarditis","volume":"10","author":"Flurin","year":"2023","journal-title":"Open Forum Infect Dis"},{"key":"2024072916052064700_ofae328-B29","doi-asserted-by":"crossref","first-page":"ofz090","DOI":"10.1093\/ofid\/ofz090","article-title":"Sustained circulating bacterial deoxyribonucleic acid is associated with complicated Staphylococcus aureus bacteremia","volume":"6","author":"Gutierrez","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2024072916052064700_ofae328-B30","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1093\/infdis\/jiad255","article-title":"Serial quantitation of plasma microbial cell-free DNA before and after diagnosis of pulmonary invasive mold infections in hematopoietic cell transplant recipients","volume":"229","author":"Heldman","year":"2023","journal-title":"J Infect Dis"},{"key":"2024072916052064700_ofae328-B31","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":"2024072916052064700_ofae328-B32"},{"key":"2024072916052064700_ofae328-B33","first-page":"231","article-title":"Budget impact of microbial cell-free DNA testing using the Karius\u00ae test as an alternative to invasive procedures in immunocompromised patients with suspected invasive fungal infections","volume":"2","author":"MacIntyre","year":"2020","journal-title":"Appl Health Econ Health Policy"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofae328\/58271390\/ofae328.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/11\/7\/ofae328\/58650903\/ofae328.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/11\/7\/ofae328\/58650903\/ofae328.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:04:24Z","timestamp":1722297864000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofae328\/7695719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,18]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,6,28]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofae328","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,6,18]]},"article-number":"ofae328"}}