Year: 2025
Type: article
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.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciaf655
Authors: Maaike C Swets, Zsuzsa Bakk, Annette C Westgeest, Felicia Ruffin, Rachel Korn, Jean-Francois Jabbour, Priscilla La, Luke Tysall, Simon Dewar, Rebecca K Sutherland, Mark G J de Boer, Geert H Groeneveld, David H Dockrell, Thomas W van der Vaart, Vance G Fowler, Clark D Russell, IDISA study team, Jan M Prins, Robin Soetekouw, Gitte van Twillert, Jan Veenstra, Bjorn L Herpers, Wouter Rozemeijer, Rogier R Jansen, Marc J M Bonten, Jan T M van der Meer
Institutions: Leiden University Medical Center, Medisch Centrum Haaglanden, Stichting Haaglanden Medisch Centrum, Leiden University, Duke University, Duke Medical Center, Edinburgh Royal Infirmary, Western General Hospital, Centre for Inflammation Research, University of Edinburgh, Amsterdam University Medical Centers, University of Amsterdam
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
OpenAlex ID: W4416746732