Clinical Subphenotypes of Staphylococcus aureus Bacteremia.

Area of Science:

• Infectious Diseases
• Clinical Microbiology
• Translational Medicine

Background:

• Staphylococcus aureus bacteremia (SAB) is a heterogeneous infection requiring better patient stratification.
• Identifying distinct patient subgroups (subphenotypes) is crucial for tailored clinical management and research.
• Current approaches lack reproducible methods for classifying SAB patients.

Purpose of the Study:

• To test the hypothesis that clinically relevant subphenotypes can be reproducibly identified in patients with SAB.
• To establish a foundation for patient stratification in clinical trials and management of SAB.
• To explore potential differential treatment effects based on identified subphenotypes.

Main Methods:

• Latent class analysis was applied to clinical data from three independent adult monomicrobial SAB cohorts (n=1430).
• Subphenotypes were identified without using outcome data, ensuring objective classification.
• Mortality and microbiologic outcomes were subsequently compared across the identified subphenotypes.

Main Results:

• Five reproducible clinical subphenotypes of SAB were identified: (A) older patients with comorbidities, (B) younger patients with catheter-associated SAB, (C) community-acquired metastatic SAB, (D) SAB with chronic kidney disease, and (E) SAB with injection drug use.
• Significant differences in survival and microbiologic outcomes were observed between subphenotypes.
• Mortality was highest in subphenotype A and lowest in B and E; microbiologic outcomes were poorest in subphenotype C.

Conclusions:

• Reproducible and clinically relevant subphenotypes for Staphylococcus aureus bacteremia have been identified.
• These subphenotypes demonstrate differential outcomes and potential for varied treatment responses.
• The identified subphenotypes offer a pathway towards personalized medicine for SAB through clinical trial enrichment and patient stratification.