{"doi":"10.1093/cid/ciaf655","title":"Reproducible Identification of <i>Staphylococcus aureus</i> Bacteremia Clinical Subphenotypes","abstract":"BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.","journal":"Clinical Infectious Diseases","year":2025,"id":548981,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1214524,"name":"Zsuzsa Bakk","orcid":"0000-0001-9352-4812","position":1,"is_corresponding":false},{"id":1030794,"name":"Annette C. Westgeest","orcid":"0000-0002-0648-3555","position":2,"is_corresponding":false},{"id":37805,"name":"Felicia Ruffin","orcid":"0000-0003-2176-6462","position":3,"is_corresponding":false},{"id":1095985,"name":"Rachel E. Korn","orcid":"0009-0007-2239-0870","position":4,"is_corresponding":false},{"id":1442651,"name":"Jean-Francois Jabbour","orcid":"0000-0002-0214-8290","position":5,"is_corresponding":false},{"id":1441674,"name":"Priscilla La","orcid":"0009-0005-7724-4753","position":6,"is_corresponding":false},{"id":1214526,"name":"Luke Tysall","orcid":"0000-0002-0966-3877","position":7,"is_corresponding":false},{"id":1215166,"name":"Simon Dewar","orcid":null,"position":8,"is_corresponding":false},{"id":1442652,"name":"Rebecca Sutherland","orcid":"0000-0001-5214-9630","position":9,"is_corresponding":false},{"id":1030798,"name":"Mark de Boer","orcid":"0000-0002-5009-6499","position":10,"is_corresponding":false},{"id":480484,"name":"Geert H. 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Veenstra","orcid":"0000-0002-2783-0018","position":20,"is_corresponding":false},{"id":863070,"name":"Bjorn L. Herpers","orcid":"0000-0003-1632-8302","position":21,"is_corresponding":false},{"id":1443130,"name":"Wouter Rozemeijer","orcid":null,"position":22,"is_corresponding":false},{"id":1443131,"name":"Rogier R. Jansen","orcid":null,"position":23,"is_corresponding":false},{"id":88037,"name":"Marc J. M. Bonten","orcid":"0000-0002-9095-9201","position":24,"is_corresponding":false},{"id":940684,"name":"Jan T. M. van der Meer","orcid":null,"position":25,"is_corresponding":false},{"id":1214523,"name":"Maaike Swets","orcid":"0000-0003-0901-9560","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41307923","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}