A study led by researchers from the Infectious Diseases Service of the Bellvitge University Hospital (HUB), the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Barcelona (UB) shows for the first time that a combination of antibiotics can significantly improve the prognosis of patients with high-risk Staphylococcus aureus bacteriemia, if it is applied selectively and in a personalized way.
The article has been published in The Lancet Regional Health—Europe and is the result of the collaboration of a dozen Spanish hospitals within the framework of the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC) of the Instituto de Salud Carlos III.
The work, with Dr. Francesc Escrihuela-Vidal (HUB, IDIBELL) as first author, has been led by Dr. Jordi Carratalà (HUB, IDIBELL, UB) together with Dr. Belén Gutiérrez-Gutiérrez (Hospital Universitario Virgen Macarena and Instituto de Biomedicina de Sevilla).
A reanalysis that redefines the strategy against bacteriemia
Bacteremia for S. aureus (i.e., the presence of bacteria in the blood) is a frequent and serious infection, with mortality reaching 30%. Its management requires prolonged intravenous antibiotherapy, the removal of possible infected devices and a thorough evaluation to rule out complications such as endocarditis or metastatic focus. In recent years, several clinical trials evaluating the combination of antibiotics had failed to demonstrate clear benefits in the global set of patients, a fact that the authors of the present study attributed to the lack of stratification according to risk.
For this reason, the study has carried out a reanalysis of the individualized data of two previously performed randomized clinical trials, differentiating patients according to their risk profile. This stratification was done through the FEN-AUREUS classification—a recently developed clinical tool that allows estimating the risk of mortality with information available during the first 24 hours of evolution—and the complication criteria of the Infectious Diseases Society of America (IDSA).
A personalized medicine according to individual risk
The re-evaluated trials include, on the one hand, a study with 155 patients from 18 Spanish hospitals that compared the use of daptomycin with the combination of daptomycin and phosphomycin; and, on the other, a study with 215 patients from 19 hospitals that compared cloxacillin in monotherapy with the combination of cloxacillin and phosphomycin. In both cases, the initial conclusions had shown no significant benefits of combined therapy in the overall set of patients, beyond a reduction in the duration of bacteriemia in patients treated with phosphomycin.
After the new risk group analysis, the work shows that low-risk and uncomplicated patients do not obtain significant benefits from combined therapy. On the other hand, high-risk patients showed remarkable therapeutic success at eight weeks (69.2% vs. 25.8%) and lower mortality at 60 days (23.1% vs. 45.2%).
According to Dr. Escrihuela-Vidal, “The integration of risk and complications criteria can help identify patients who can really benefit from combined therapy.”
Dr. Carratalà points out, “The results represent a real paradigm shift in the approach to this infection: we move from a uniform strategy for all patients to a precision medicine based on individual risk.”
In addition, the findings highlight that this approach avoids unnecessary intensive treatments in low-risk patients and will contribute to improving the design of future clinical trials.
More information
Francesc Escrihuela-Vidal et al, Subphenotype- and complication-guided adjunctive fosfomycin versus standard monotherapy in Staphylococcus aureus bacteraemia: pooled analysis of two randomised trials, The Lancet Regional Health – Europe (2026). DOI: 10.1016/j.lanepe.2026.101611
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