{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:45:47Z","timestamp":1789238747702,"version":"build-2803163510"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Edinburgh Clinical Academic Track"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["214178\/Z\/18\/Z"],"award-info":[{"award-number":["214178\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000589","name":"Chief Scientist Office","doi-asserted-by":"publisher","award":["PCL\/25\/21"],"award-info":[{"award-number":["PCL\/25\/21"]}],"id":[{"id":"10.13039\/501100000589","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012923","name":"Royal College of Physicians of Edinburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI165671"],"award-info":[{"award-number":["R01-AI165671"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020643","name":"MRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020643","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000317","name":"AMR","doi-asserted-by":"publisher","award":["MR\/NO2995X\/1"],"award-info":[{"award-number":["MR\/NO2995X\/1"]}],"id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clinical heterogeneity in Staphylococcus aureus bacteremia (SAB) complicates clinical management and research. We have previously identified 5 clinically distinct subphenotypes of SAB associated with differences in outcomes and response to adjunctive rifampicin. Here, we aimed to identify these subphenotypes in geographically diverse observational cohorts, including a higher prevalence of methicillin-resistant S. aureus (MRSA) bacteremia and the USA300 clone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied 3 cohorts of adults with SAB from observational studies: a UK retrospective study (Edinburgh cohort 2; n = 463); a Dutch prospective study (IDISA [Improved Diagnostic Strategies in Staphylococcus aureus bacteremia study]; n = 490); and a prospective US study (SABG-PCS [Staphylococcus aureus Bacteremia Group Prospective Cohort Study]; n = 755). Subphenotypes were identified from routinely available clinical data using latent class analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients from the SABG-PCS cohort had greater multimorbidity and more MRSA bacteremia (40.2% [303 of 755]), including infection with the USA300 clone (14.7% [111 of 755]). Five distinct subphenotypes were identified in each cohort: (1) older age and cardiometabolic multimorbidity; (2) nosocomial acquisition and intravenous catheter portal of entry; (3) community acquisition and metastatic infection; (4) chronic kidney disease; and (5) younger age, injection drug use, and metastatic infection. Bacterial genotypes varied substantially between the Edinburgh 2 and SABG-PCS cohorts but did not differ between subphenotypes within each cohort. 90-day mortality was highest in subphenotype A, and persistent bacteremia in subphenotypes C and E.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We have reproducibly identified 5 clinical subphenotypes of SAB in observational cohorts including diverse bacterial genetic lineages and a cohort with a high prevalence of MRSA and USA300 bacteremia. These robustly reproducible clinical subphenotypes provide a framework to rationalize the heterogeneity intrinsic to SAB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf655","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:29:47Z","timestamp":1764260987000},"page":"e643-e651","source":"Crossref","is-referenced-by-count":4,"title":["Reproducible Identification of\n                    <i>Staphylococcus aureus<\/i>\n                    Bacteremia Clinical Subphenotypes"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0901-9560","authenticated-orcid":false,"given":"Maaike C","family":"Swets","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Leiden University Medical Center, Leiden University , Leiden ,","place":["The Netherlands"]},{"name":"Department of Internal Medicine, Haaglanden Medical Center , The Hague ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsa","family":"Bakk","sequence":"additional","affiliation":[{"name":"Department of Methodology and Statistics, Leiden University , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0648-3555","authenticated-orcid":false,"given":"Annette C","family":"Westgeest","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Leiden University Medical Center, Leiden University , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2176-6462","authenticated-orcid":false,"given":"Felicia","family":"Ruffin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2239-0870","authenticated-orcid":false,"given":"Rachel","family":"Korn","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0214-8290","authenticated-orcid":false,"given":"Jean-Francois","family":"Jabbour","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7724-4753","authenticated-orcid":false,"given":"Priscilla","family":"La","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0966-3877","authenticated-orcid":false,"given":"Luke","family":"Tysall","sequence":"additional","affiliation":[{"name":"Medical Microbiology, Royal Infirmary of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Dewar","sequence":"additional","affiliation":[{"name":"Medical Microbiology, Royal Infirmary of Edinburgh , Edinburgh ,","place":["United Kingdom"]},{"name":"Clinical Infection Research Group, Western General Hospital , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca K","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Clinical Infection Research Group, Western General Hospital , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-6499","authenticated-orcid":false,"given":"Mark G J","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Leiden University Medical Center, Leiden University , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert H","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Leiden University Medical Center, Leiden University , Leiden ,","place":["The Netherlands"]},{"name":"Department of Internal Medicine-Acute Internal Medicine, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-4861","authenticated-orcid":false,"given":"David H","family":"Dockrell","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5873-0474","authenticated-orcid":false,"given":"Thomas W","family":"van der Vaart","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Amsterdam UMC, University of Amsterdam , Amsterdam, T","place":["he Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-0897","authenticated-orcid":false,"suffix":"Jr","given":"Vance G","family":"Fowler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]},{"name":"Infectious Diseases, Duke Clinical Research Institute , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-8243","authenticated-orcid":false,"given":"Clark D","family":"Russell","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"IDISA study team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M","family":"Prins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Soetekouw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte","family":"van Twillert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Veenstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn L","family":"Herpers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Rozemeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier R","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J M","family":"Bonten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan T M","family":"van der Meer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"2026043013095328600_ciaf655-B1","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1001\/jama.2025.4288","article-title":"Management of Staphylococcus aureus bacteremia: a review","volume":"334","author":"Tong","year":"2025","journal-title":"JAMA"},{"key":"2026043013095328600_ciaf655-B2","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0140-6736(22)02185-7","article-title":"Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"400","author":"GBD 2019 Antimicrobial Resistance Collaborators","year":"2022","journal-title":"Lancet"},{"key":"2026043013095328600_ciaf655-B3","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/cid\/ciae281","article-title":"Distinct clinical endpoints of Staphylococcus aureus bacteraemia complicate assessment of outcome","volume":"79","author":"Russell","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026043013095328600_ciaf655-B4","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1038\/s41591-023-02569-0","article-title":"Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial","volume":"29","author":"Grillo","year":"2023","journal-title":"Nat Med"},{"key":"2026043013095328600_ciaf655-B5","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/infdis\/jiac219","article-title":"Heterogeneity in Staphylococcus aureus bacteraemia clinical trials complicates interpretation of findings","volume":"226","author":"Dolby","year":"2022","journal-title":"J Infect Dis"},{"key":"2026043013095328600_ciaf655-B6","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1093\/cid\/ciae338","article-title":"Clinical sub-phenotypes of Staphylococcus aureus bacteraemia","volume":"79","author":"Swets","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026043013095328600_ciaf655-B7","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1007\/s00134-024-07665-4","article-title":"Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis","volume":"50","author":"Baillie","year":"2024","journal-title":"Intensive Care Med"},{"key":"2026043013095328600_ciaf655-B8","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S0140-6736(17)32456-X","article-title":"Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial","volume":"391","author":"Thwaites","year":"2018","journal-title":"Lancet"},{"key":"2026043013095328600_ciaf655-B9","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.cmi.2022.03.015","article-title":"Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis","volume":"28","author":"Bai","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"2026043013095328600_ciaf655-B10","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1093\/cid\/ciz112","article-title":"Changing characteristics of Staphylococcus aureus bacteremia: results from a 21-year, prospective, longitudinal study","volume":"69","author":"Souli","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2026043013095328600_ciaf655-B11","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.jinf.2010.09.021","article-title":"Association of methicillin-resistant Staphylococcus aureus (MRSA) USA300 genotype with mortality in MRSA bacteremia","volume":"61","author":"Kempker","year":"2010","journal-title":"J Infect"},{"key":"2026043013095328600_ciaf655-B12","doi-asserted-by":"crossref","first-page":"ofac653","DOI":"10.1093\/ofid\/ofac653","article-title":"All-cause and infection-related mortality in Staphylococcus aureus bacteremia, a multicenter prospective cohort study","volume":"9","author":"van der Vaart","year":"2022","journal-title":"Open Forum Infect Dis"},{"key":"2026043013095328600_ciaf655-B13","doi-asserted-by":"crossref","first-page":"791","DOI":"10.7326\/0003-4819-137-10-200211190-00007","article-title":"Health care\u2013associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections","volume":"137","author":"Friedman","year":"2002","journal-title":"Ann Intern Med"},{"key":"2026043013095328600_ciaf655-B14","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/S1473-3099(20)30447-3","article-title":"Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study","volume":"20","author":"Kuehl","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2026043013095328600_ciaf655-B15","volume-title":"Technical guide for latent GOLD 5.1: basic, advanced, and syntax","author":"Magdison","year":"2016"},{"key":"2026043013095328600_ciaf655-B16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1093\/pan\/mpq025","article-title":"Latent class modeling with covariates: two improved three-step approaches","volume":"18","author":"Vermunt","year":"2010","journal-title":"Polit Anal"},{"key":"2026043013095328600_ciaf655-B17","volume-title":"LG-syntax user's guide: manual for latent gold syntax module version 6.0","author":"Vermunt","year":"2021"},{"key":"2026043013095328600_ciaf655-B18","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s10096-019-03777-8","article-title":"Population-based risk factors for community-onset bloodstream infections","volume":"39","author":"Laupland","year":"2020","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2026043013095328600_ciaf655-B19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1053\/j.ackd.2019.01.004","article-title":"Immune dysfunction and risk of infection in chronic kidney disease","volume":"26","author":"Syed-Ahmed","year":"2019","journal-title":"Adv Chronic Kidney Dis"},{"key":"2026043013095328600_ciaf655-B20","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1159\/000330673","article-title":"Chronic kidney disease and risk of death from infection","volume":"34","author":"Wang","year":"2011","journal-title":"Am J Nephrol"},{"key":"2026043013095328600_ciaf655-B21","doi-asserted-by":"crossref","first-page":"10539","DOI":"10.1038\/srep10539","article-title":"Chronic kidney disease is associated with a higher 90-day mortality than other chronic medical conditions in patients with sepsis","volume":"5","author":"Mansur","year":"2015","journal-title":"Sci Rep"},{"key":"2026043013095328600_ciaf655-B22","doi-asserted-by":"crossref","first-page":"e209","DOI":"10.1016\/S1473-3099(24)00065-3","article-title":"Eligibility of patients with Staphylococcus aureus bacteraemia for early oral switch","volume":"24","author":"Cooper","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"2026043013095328600_ciaf655-B23","doi-asserted-by":"crossref","first-page":"103240","DOI":"10.1016\/j.eclinm.2025.103240","article-title":"Identification and validation of clinical phenotypes in Staphylococcus aureus bloodstream infection and their association with mortality (FEN-AUREUS study)","volume":"83","author":"Guti\u00e9rrez-Guti\u00e9rrez","year":"2025","journal-title":"eClinicalMedicine"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciaf655\/65573029\/ciaf655.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/82\/4\/e643\/65573029\/ciaf655.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/82\/4\/e643\/65573029\/ciaf655.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:10:00Z","timestamp":1777569000000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/82\/4\/e643\/8346134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,11,27]]},"published-print":{"date-parts":[[2026,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciaf655","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4,15]]},"published":{"date-parts":[[2025,11,27]]}}}