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Genotyping of Staphylococcus aureus by Ribosomal Spacer PCR RS-PCR
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Reproducible Identification of Staphylococcus aureus Bacteremia Clinical Subphenotypes.

Maaike C Swets1,2, Zsuzsa Bakk3, Annette C Westgeest1

  • 1Department of Infectious Diseases, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|November 27, 2025
PubMed
Summary

Five distinct Staphylococcus aureus bacteremia (SAB) subphenotypes were identified across diverse patient groups. These reproducible findings help explain SAB

Keywords:
Staphylococcus aureusMRSAbacteremiapatient stratificationsubphenotypes

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Area of Science:

  • Clinical microbiology and infectious diseases.
  • Epidemiology of bacterial infections.
  • Patient stratification and personalized medicine.

Background:

  • Staphylococcus aureus bacteremia (SAB) exhibits significant clinical heterogeneity, complicating management and research.
  • Previous work identified five SAB subphenotypes linked to outcomes and rifampicin response.
  • This study aimed to validate these subphenotypes in diverse international cohorts, including those with high rates of methicillin-resistant S. aureus (MRSA).

Purpose of the Study:

  • To identify and validate five distinct clinical subphenotypes of Staphylococcus aureus bacteremia (SAB) in geographically diverse observational cohorts.
  • To assess the reproducibility of these subphenotypes across different patient populations, including those with a high prevalence of MRSA and the USA300 clone.

Main Methods:

  • Analysis of three adult SAB cohorts: UK (n=463), Netherlands (n=490), and USA (n=755).
  • Latent class analysis applied to routinely collected clinical data to identify subphenotypes.
  • Inclusion of data on patient demographics, acquisition source, comorbidities, and bacterial genotypes.

Main Results:

  • Five reproducible clinical subphenotypes were identified in all cohorts: (A) older, cardio-metabolic issues; (B) nosocomial, catheter-related; (C) community-acquired, metastatic infection; (D) chronic kidney disease; (E) younger, injection drug use, metastatic infection.
  • The USA cohort showed higher multimorbidity and MRSA (40.2%), including USA300 (14.7%).
  • Subphenotype A had the highest 90-day mortality; subphenotypes C and E experienced persistent bacteremia.

Conclusions:

  • Five clinical subphenotypes of SAB are robustly reproducible across diverse observational cohorts, including those with high MRSA and USA300 prevalence.
  • These identified subphenotypes offer a framework for understanding and managing the inherent clinical heterogeneity of SAB.
  • The findings support the use of these subphenotypes for stratifying patients in future clinical trials and management strategies.