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.

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Key information

Conditions

Staphylococcal Aureus Infection Staphylococcus Aureus Bacteraemia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for the present study: all patients included in the BACSAFO cohort, composed of all patients included in the intention-to-treat populations of the BACSARM and SAFO randomised clinical trials (RCT).

Inclusion criteria

for the BACSARM and SAFO RCTs:

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

Common exclusion criteria for the BACSARM and SAFO RCTs:

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
Pregnancy at the time of inclusion
Inclusion in another clinical trial

Particular exclusion criteria for the BACSARM RCT:

Diagnosis of MRSA pneumonia
Prior history of eosinophilic pneumonia
Use of additional antibiotic therapy with microbiological activity against MRSA

Particular exclusion criteria for the SAFO RCT:

Prior history of myasthenia gravis
Acute SARS-CoV2 infection

Treatment and study plan

Primary outcomes

All-cause mortality at 60 days

Time frame: At 60 days from randomisation

All-cause mortality at 60 days after randomisation

Secondary outcomes

All-cause mortality at 30 days

Time frame: At 30 days after randomisation

All-cause mortality at 30 days after randomisation
Treatment success at 8 weeks

Time frame: At 8 weeks after randomisation

Survival without clinical relapse and with resolution of symptoms at 8 weeks after randomisation

Sponsors and collaborators

Lead sponsor

Hospital Universitari de Bellvitge

Other

Collaborators

Hospital Universitario Virgen Macarena
Institut d'Investigació Biomèdica de Bellvitge
University of Barcelona
University of Seville

Registry information

Official study title

Subphenotype- and Complication-guided Adjunctive Fosfomycin Therapy for Staphylococcus Aureus Bacteraemia: Pooled Analysis of Two Randomised Trials

Important dates

Study start: 2025
Primary completion: 2025
Study completion: 2025
First posted: Sep 4, 2025
Registry last updated: Sep 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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