{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:57:41Z","timestamp":1785848261917,"version":"3.56.0"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>Determination of pathogen-specific bacterial DNA load (BDL) in blood has been shown to be directly correlated with severity of infection in patients with bacteremia. In the diagnostic work-up of patients with <jats:italic>Staphylococcus aureus<\/jats:italic> bacteremia (SAB), determination of the primary focus is imperative, because of implications for treatment duration, and ultimately prognosis. Here we investigate whether measurement of BDL in patients with SAB can distinguish between intravascular and extravascular foci of infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In a consecutive cohort of 43 patients with positive blood cultures with <jats:italic>Staphylococcus aureus<\/jats:italic>, we performed a quantitative PCR on whole blood to detect the bacterial DNA load. Infections were classified into 3 categories: i) soft tissue infections and phlebitis, ii) deep-seated infections and iii) endocarditis and other intravascular infections. Bacterial DNA loads and inflammatory parameters in the three categories were analyzed and compared.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Median BDL in patients with endocarditis and other intravascular infections was 1015 cfu\/ml, significantly higher than BDL in the other two categories (28 and 31 cfu\/ml respectively). In contrast, CRP and leukocytes were not significantly different between the three patient categories. BDL could be detected in all patients with intravascular causes and levels were generally 10\u201330 times higher than in the other infection categories. Median BDL in non-survivors was 85 cfu\/ml, which was higher than in survivors with a median BDL of 29 cfu\/ml, although not significant.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In <jats:italic>Staphylococcus aureus<\/jats:italic> bacteremia pathogen-specific BDL is distinctly higher in patients with intravascular infections compared to extravascular origins. As measurement of BDL by PCR can easily be implemented in routine diagnostics, it can improve the diagnostic work-up of SAB by rapidly identifying the subset of patients who need higher dosages of antibiotics and additional measures to improve outcome.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0266869","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T17:34:19Z","timestamp":1650476059000},"page":"e0266869","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bacterial DNA load in Staphylococcus aureus bacteremia is significantly higher in intravascular infections"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-5248","authenticated-orcid":true,"given":"An-Emmie","family":"Nieman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Rozemeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H. M.","family":"Savelkoul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier P.","family":"Schade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"pone.0266869.ref001","article-title":"[Evaluation of diagnosis and therapy of Staphylococcus aureus bacteraemia: recommended minimum treatment duration of 2 weeks not always met].","author":"GWD Landman","year":"2011","journal-title":"Ned Tijdschr Geneeskd."},{"key":"pone.0266869.ref002","article-title":"SWAB guidelines for Antibacterial therapy of adult patients with Sepsis.","volume":"49","author":"SWAB","year":"2010","journal-title":"Sticht Werkgr Antibiot"},{"key":"pone.0266869.ref003","first-page":"1","article-title":"Clinical Practice Guidlines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America","volume":"49","author":"NPO Grady","year":"2014","journal-title":"Clin Infect Dis"},{"key":"pone.0266869.ref004","author":"D Society","year":"2018","journal-title":"SWAB guidelines for the antimicrobial treatment of infective endocarditis"},{"key":"pone.0266869.ref005","article-title":"2015 ESC guidelines for the management of infective endocarditis: The task force for the management of infective endocarditis of the European society of cardiology (ESC): Endorsed by: European association for cardio-thoracic surgery (EACTS), the European.","author":"G Habib","year":"2016","journal-title":"Russian Journal of Cardiology."},{"key":"pone.0266869.ref006","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1001\/archinte.163.17.2066","article-title":"Clinical Identifiers of Complicated S. aureus bacteremia","volume":"163","author":"VG Fowler","year":"2003","journal-title":"Arch Intern Med"},{"key":"pone.0266869.ref007","author":"A Wang","year":"2018","journal-title":"Management Considerations in Infective Endocarditis A Review"},{"key":"pone.0266869.ref008","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1086\/432472","article-title":"Time to positivity in Staphylococcus aureus bacteremia: Possible correlation with the source and outcome of infection","volume":"41","author":"R Khatib","year":"2005","journal-title":"Clin Infect Dis"},{"key":"pone.0266869.ref009","article-title":"Time to blood culture positivity in Staphylococcus aureus bacteraemia to determine risk of infective endocarditis","author":"F Kahn","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"pone.0266869.ref010","article-title":"Evaluation of a real-time PCR assay for detection and quantification of bacterial DNA directly in blood of preterm neonates with suspected late-onset sepsis","author":"M van den Brand","year":"2018","journal-title":"Crit Care"},{"key":"pone.0266869.ref011","article-title":"Severity of pneumococcal pneumonia associated with genomic bacterial load.","author":"J Rello","year":"2009","journal-title":"Chest"},{"key":"pone.0266869.ref012","article-title":"Severity of Meningococcal Disease Associated with Genomic Bacterial Load","author":"T Darton","year":"2009","journal-title":"Clin Infect Dis"},{"key":"pone.0266869.ref013","article-title":"High pneumococcal DNA load, procalcitonin and suPAR levels correlate to severe disease development in patients with pneumococcal pneumonia","author":"AJM Loonen","year":"2017","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"pone.0266869.ref014","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1128\/JCM.01197-08","article-title":"High levels of mecA DNA detected by a quantitative real-time PCR assay are associated with mortality in patients with methicillin-resistant Staphylococcus aureus bacteremia","volume":"47","author":"YC Ho","year":"2009","journal-title":"J Clin Microbiol"},{"key":"pone.0266869.ref015","article-title":"Time to blood culture positivity as a predictor of clinical outcome of Staphylococcus aureus bloodstream infection","author":"AR Marra","year":"2006","journal-title":"J Clin Microbiol"},{"key":"pone.0266869.ref016","article-title":"Thirty-day mortality in UK patients with community-onset and hospital-acquired meticillin-susceptible Staphylococcus aureus bacteraemia.","author":"M Melzer","year":"2013","journal-title":"J Hosp Infect."},{"key":"pone.0266869.ref017","article-title":"Resilience of the Pitt Bacteremia Score: Three Decades and Counting","author":"MN Al-Hasan","year":"2019","journal-title":"Clin Infect Dis"},{"key":"pone.0266869.ref018","article-title":"Proposed Modifications to the Duke Criteria for the Diagnosis of Infective Endocarditis","author":"JS Li","year":"2002","journal-title":"Clin Infect Dis"},{"key":"pone.0266869.ref019","article-title":"Species-specific and ubiquitous-DNA-based assays for rapid identification of Staphylococcus aureus","author":"F Martineau","year":"1998","journal-title":"J Clin Microbiol"},{"key":"pone.0266869.ref020","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/23744235.2018.1562205","article-title":"High nuc DNA load in whole blood is associated with sepsis, mortality and immune dysregulation in Staphylococcus aureus bacteraemia.","volume":"51","author":"I Ziegler","year":"2019","journal-title":"Infect Dis (Auckl)."},{"key":"pone.0266869.ref021","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ofid\/ofz126","article-title":"Prognostic power of pathogen cell-free DNA in staphylococcus aureus bacteremia","volume":"6","author":"AO Guimaraes","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"pone.0266869.ref022","doi-asserted-by":"crossref","first-page":"e72349","DOI":"10.1371\/journal.pone.0072349","article-title":"Comparison of pathogen DNA isolation methods from large volumes of whole blood to improve molecular diagnosis of bloodstream infections","volume":"8","author":"AJM Loonen","year":"2013","journal-title":"PLoS One"},{"key":"pone.0266869.ref023","article-title":"A nanoparticle-based method for culture-free bacterial DNA enrichment from whole blood","author":"MM Hassan","year":"2018","journal-title":"Biosens Bioelectron"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T17:34:38Z","timestamp":1650476078000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266869"}},"subtitle":[],"editor":[{"given":"Adriana","family":"Calderaro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0266869","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}