Subphenotype- and Complication-guided Adjunctive Fosfomycin Therapy for Staphylococcus Aureus Bacteraemia

Staphylococcus aureus bacteraemia (SAB) is a major global cause of sepsis-related mortality. Randomised trials of adjunctive antibiotics, including fosfomycin, have not shown consistent benefit, possibly due to inclusion of unselected SAB populations. The FEN-AUREUS classification enables early risk stratification based on clinical subphenotypes. The investigators aim to validate this framework in a pooled trial cohort and assess whether combining subphenotypes with IDSA-defined complicated SAB could identify patients most likely to benefit from adjunctive fosfomycin. The investigators will conduct a post-hoc analysis of individual-level data from two multicentre randomised trials-BACSARM and SAFO-evaluating fosfomycin in SAB. Participants will be classified using FEN-AUREUS into source phenotypes (A, B and C) and risk subphenotypes (1 = low-risk, 2 = high-risk). Associations between subphenotype, treatment arm, and outcomes (30/60-day mortality, 8-week treatment success) will be assessed using multivariable models. Monte Carlo simulations will explore power by subgroup. FEN-AUREUS subphenotypes combined with complication status have the potential to identify patients with SAB that could likely benefit form combination therapy with fosfomycin.

NCT Number	NCT07155590
Lead Sponsor	Hospital Universitari de Bellvitge Collaborators: Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, Hospital Universitario Virgen Macarena, University of Seville
Conditions	Staphylococcal Aureus Infection, Staphylococcus Aureus Bacteraemia
Enrollment	369 participants
Start Date	2025-07-21
Primary Completion	2025-08-04 (estimated)
Study Completion	2025-09-15 (estimated)
Updated on ClinicalTrials.gov	2025-09-11