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

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

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT07155590

Enrollment

369

Registered

2025-09-04

Start date

2025-07-21

Completion date

2025-09-15

Last updated

2025-09-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

OTHER

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
All-cause mortality at 60 days	At 60 days from randomisation	All-cause mortality at 60 days after randomisation

Secondary

Measure	Time frame	Description
All-cause mortality at 30 days	At 30 days after randomisation	All-cause mortality at 30 days after randomisation
Treatment success at 8 weeks	At 8 weeks after randomisation	Survival without clinical relapse and with resolution of symptoms at 8 weeks after randomisation

Countries

Spain

Outcome results