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

NCT07155590 | Active Not Recruiting

• 1 other identifier: FENAUREUS-BACSAFO
• Study Type: observational
• Target: 369
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Staphylococcal Aureus Infection; Staphylococcus Aureus Bacteraemia

Keywords

Staphylococcus aureus bacteraemia; Risk stratification; Clinical phenotypes; Subphenotypes; Monotherapy; Adjunctive therapy; Fosfomycin; Complicated bacteraemia; Randomised clinical trials

Outcome Measures

Primary Outcomes (1)

• All-cause mortality at 60 days

  All-cause mortality at 60 days after randomisation

  At 60 days from randomisation

Secondary Outcomes (2)

• All-cause mortality at 30 days

  At 30 days after randomisation

• Treatment success at 8 weeks

  At 8 weeks after randomisation

Study Arms (2)

Adjunctive fosfomycin therapy

Patients with Staphylococcus aureus bacteraemia from the BACSAFO cohort treated with any regimen including fosfomycin

Monotherapy

Patients with Staphylococcus aureus bacteraemia from the BACSAFO cohort treated with any regimen not containing fosfomycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The BACSAFO cohort pools individual participant data from two multicentre, randomised, superiority trials evaluating adjunctive fosfomycin for the treatment of SAB: BACSARM and SAFO. The BACSARM trial included 155 adult patients with methicillin-resistant (MRSA), randomised 1:1 to receive either daptomycin alone or daptomycin plus fosfomycin. The SAFO trial enrolled 214 adult patients with methicillin-susceptible (MSSA) bacteraemia, randomised to cloxacillin alone or cloxacillin plus fosfomycin.

You may qualify if:

• \> or = 18 years old
• Monomicrobial Staphylococcus aureus bacteraemia
• Evidence of active infection

You may not qualify if:

• Polymicrobial bacteraemia
• Severe clinical status with expected survival \< 24 hours
• Severe liver disease with Child-Pugh score class C
• Diagnosis of prosthetic infective endocarditis
• Allergy or known resistance to study drugs
• Diagnosis of MRSA pneumonia
• Prior history of eosinophilic pneumonia
• Use of additional antibiotic therapy with microbiological activity against MRSA
• Prior history of myasthenia gravis
• Acute SARS-CoV2 infection

Sponsors & Collaborators

• Hospital Universitari de Bellvitge: lead
• Institut d'Investigació Biomèdica de Bellvitge: collaborator
• University of Barcelona: collaborator
• Hospital Universitario Virgen Macarena: collaborator
• University of Seville: collaborator

Study Sites (2)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Hospital Universitario Virgen de Macarena

Seville, 41009, Spain

Location

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: September 4, 2025
• Study Start: July 21, 2025
• Primary Completion: August 4, 2025
• Study Completion: September 15, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

ES (2)