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We contend that investigating SAB as a single disease is impeding the identification of beneficial therapeutic approaches. Recently, three data-driven approaches for patient stratification in SAB have been reported, using routinely available data to identify clinically distinct subphenotypes with differences in mortality, microbiologic outcomes, and response to adjunctive antimicrobial therapies (the Swets et al, FEN-AUREUS, and MRSA-GEIRAS-SEIMC studies). In this review, we compare the methodologies and findings from these studies, discuss their limitations, and identify goals for future research in this space. We expect that transformative advances in SAB management will only be achieved by addressing clinical and biological heterogeneity, enabling progress from observable clinical subphenotypes to mechanism-based endotypes defined by treatable traits.<\/jats:p>","DOI":"10.1093\/infdis\/jiag327","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:51:40Z","timestamp":1781869900000},"page":"e441-e451","source":"Crossref","is-referenced-by-count":1,"title":["Rationalizing Heterogeneity in\n                    <i>Staphylococcus aureus<\/i>\n                    Bacteremia: Current Progress and Future Goals"],"prefix":"10.1093","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-8243","authenticated-orcid":false,"given":"Clark D","family":"Russell","sequence":"first","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh ,","place":["United Kingdom"]},{"name":"Baillie Gifford Pandemic Science Hub, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh ,","place":["United Kingdom"]},{"name":"Clinical Infection Research Group Edinburgh, Western General Hospital , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1371-6417","authenticated-orcid":false,"given":"Sof\u00eda","family":"De La Villa","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid\/Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) , Madrid ,","place":["Spain"]},{"name":"Biomedical Research Networking Centre for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0901-9560","authenticated-orcid":false,"given":"Maaike C","family":"Swets","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Haaglanden Medical Center , The Hague ,","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":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden University , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Zumbo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Microbiology, Virgen Macarena University Hospital , Seville ,","place":["Spain"]},{"name":"Department of Medicine, University of Seville , Seville ,","place":["Spain"]},{"name":"Institute of Biomedicine of Seville (IBiS)\/CSIC , Seville ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-5583","authenticated-orcid":false,"given":"Patricia","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid\/Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) , Madrid ,","place":["Spain"]}],"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"]},{"name":"Clinical Infection Research Group Edinburgh, Western General Hospital , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9668-0770","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Guti\u00e9rrez-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III , Madrid ,","place":["Spain"]},{"name":"Division of Infectious Diseases and Microbiology, Virgen Macarena University Hospital , Seville ,","place":["Spain"]},{"name":"Department of Medicine, University of Seville , Seville 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