{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:10:05Z","timestamp":1786641005156,"version":"build-2736575974"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"from Karius, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Staphylococcus aureus bacteremia in patients with cardiac implantable electronic devices (CIEDs) is often associated with infective endocarditis (CIED-IE). The CIED-IE diagnosis is syndromic. Diagnostic uncertainty is common. Frequently, these patients are classified as having possible CIED-IE, resulting in guideline-noncompliant treatment and heterogeneous outcomes. Improved outcomes require accurate diagnoses. In these patients, we evaluated whether metagenomic sequencing of microbial cell-free DNA (mcfDNA) in serial plasma specimens could improve diagnostic precision.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied 16 patients with staphylococcal bacteremia who were classified with definite or possible CIED-IE and recommended for device removal, if there was a positive blood culture within 7 days and no concurrent deep infection. Plasma specimens obtained at consent, before extraction, and during 96\u2005hours after extraction underwent metagenomic sequencing and quantification of staphylococcal mcfDNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 10 of 11 patients with definite CIED-IE, mcfDNA persisted during antibiotic therapy for prolonged durations (median, 11 days [interquartile range {IQR}, 7.5\u201315 days]). In these cases, mcfDNA concentration in plasma obtained early after lead extraction increased significantly and thereafter decreased rapidly. In 5 cases of possible CIED-IE, mcfDNA was undetectable after 6 days (IQR, 5.5\u20137.5 days) of antibiotic therapy and remained undetectable after CIED extraction. These mcfDNA patterns differ significantly (P = .001), suggesting 2 distinct patient populations: 1 with definite CIED-IE and 1 without lead infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>If confirmed, these mcfDNA patterns can serve as biomarkers, together with clinical features, to improve precision in diagnosing or rejecting S. aureus CIED-IE. Strategically timed mcfDNA testing before and after CIED extraction may aid in planning therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf113","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:15:53Z","timestamp":1741565753000},"page":"748-755","source":"Crossref","is-referenced-by-count":9,"title":["Quantitative Microbial Cell-Free DNA Sequencing From Plasma: A Potential Biomarker for the Diagnosis of Staphylococcal Infection of Cardiac Implantable Electronic Devices"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5113-6395","authenticated-orcid":false,"given":"Adolf W","family":"Karchmer","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0201-4266","authenticated-orcid":false,"given":"N Jenifer","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Y","family":"Park","sequence":"additional","affiliation":[{"name":"Medical Affairs, Karius, Inc , Redwood City, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronuk M","family":"Modi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7940-4320","authenticated-orcid":false,"given":"Ahmed","family":"Abdul-Azim","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Robert Wood Johnson University Hospital, Rutgers Robert Wood Johnson Medical School , New Brunswick, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polly","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Infectious Diseases, Pennsylvania Hospital, University of Pennsylvania School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D","family":"Matos","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4241-3586","authenticated-orcid":false,"given":"Daniel B","family":"Kramer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Zimetbaum","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"2025110901581097400_ciaf113-B1","doi-asserted-by":"crossref","first-page":"ofae515","DOI":"10.1093\/ofid\/ofae515","article-title":"Incidence of Staphylococcus aureus bacteremia in patients following implantation of cardiac implantable electronic devices: a Danish nationwide cohort study","volume":"11","author":"Bengtsen","year":"2024","journal-title":"Open Forum Infect Dis"},{"key":"2025110901581097400_ciaf113-B2","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1080\/23744235.2020.1799070","article-title":"Does extraction of cardiac implantable electronic devices improve outcome in patients with Staphylococcus aureus bacteraemia?","volume":"52","author":"Snygg-Martin","year":"2020","journal-title":"Infect Dis (Lond)"},{"key":"2025110901581097400_ciaf113-B3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1161\/CIRCEP.114.002199","article-title":"Predicting risk of endovascular device infection in patients with Staphylococcus aureus bacteremia (PREDICT-SAB)","volume":"8","author":"Sohail","year":"2015","journal-title":"Circ Arrhythm 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