ArticleEClinicalMedicine2025
Identification and validation of clinical phenotypes in
Article in EClinicalMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Article
- Rationalizing Heterogeneity in Staphylococcus aureus Bacteremia: Current Progress and Future Goals.The Journal of infectious diseases · 2026Review
- Empirical Antibiotic Activity and Outcomes in Pediatric Gram-negative Bloodstream Infections: A Rank-based Composite Outcome Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Impact of Methicillin Resistance on Outcomes ofOpen forum infectious diseases · 2026Article
- Reproducible Identification of Staphylococcus aureus Bacteremia Clinical Subphenotypes.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Observational
- Subphenotype- and complication-guided adjunctive fosfomycin versus standard monotherapy inThe Lancet regional health. Europe · 2026Article
- [Staphylococcus aureus bacteremia: the long road to adequate therapy : Recent studies].Innere Medizin (Heidelberg, Germany) · 2026Review
- Analysis of Clinical Subphenotypes in Methicillin-ResistantOpen forum infectious diseases · 2025Article
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Authors and funding
29 authors.
Funding
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Abstract
Background: Methods: Phenotypes were derived using two-stage cluster analysis of 2128 patients from the ISAC cohort (recruited between 2013 and 2015), analysing 62 variables. Cox regression assessed phenotype-mortality associations. Logistic regression was employed to develop a simplified probabilistic model for sub-phenotype allocation, validated in two external international cohorts: INSTINCT (1217 patients, recruited between 2006 and 2011) and FEN-AUREUS (1185 patients, recruited between January 2021 and October 2024). The association between sub-phenotypes and 30-day mortality in the validation cohorts was also assessed. Findings: Cluster analysis identified three clinical phenotypes based on the probable portal of entry: A (skin and soft tissues), 458 cases; B (vascular device-associated), 573 cases; and C (other portals of entry or unknown), 1097 cases. Their 30-day mortality was significantly different (13·1%, 18·2% and 25·3%, respectively, p < 0·001). Each phenotype contained two sub-phenotypes with differing characteristics and mortality risks. Also, three phenotypes were found in the INSTINCT cohort, which clustered on the same portals of entry, with two sub-phenotypes in each. When the simplified probabilistic model was applied, the sub-phenotypes showed significant associations with 30-day mortality in both validation cohorts. In INSTINCT, the aHRs were 1·93 (A2 vs A1), 3·40 (B2 vs B1), and 3·04 (C2 vs C1). In FEN-AUREUS, the aHRs were 2·02 (A2 vs A1), 2·11 (B2 vs B1), and 2·44 (C2 vs C1). Interpretation: Patients with SAB can be classified into phenotypes and sub-phenotypes, each exhibiting considerable variations in mortality rates. To facilitate clinical application, a validated open-access algorithm and calculator for phenotype and sub-phenotype assignment have been developed, enabling their use at the time of SAB confirmation. This tool aims to support timely and personalised patient care. Funding: Instituto de Salud Carlos III, Spanish Ministry of Science, Innovation and Universities (PI21/01801).
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