{
  "abstract": "Introduction Staphylococcus aureus (S. aureus) bacteraemia is a common and severe infection. With mortality rates ranging from 20–30% and long-term impairments in over a third of survivors, better treatments are urgently needed. Linezolid, a well-established treatment for pneumonia and complicated skin infections, has been shown in preclinical studies to strongly suppress S. aureus virulence factors critical to bacterial persistence and tissue damage. Hence, we aim to investigate whether the addition of linezolid to standard therapy in patients with S. aureus bacteraemia leads to an overall improvement in patient-relevant outcomes.Methods and analysis We will conduct a two-arm, parallel-group, multicentre, randomised controlled trial (Linezolid Plus Standard of Care) in 12 hospitals in Switzerland with blinded treating physicians, patients and outcome assessors. Hospitalised patients aged ≥18 years with S. aureus bacteraemia will be eligible. Patients will receive standard antibiotic treatment as prescribed by the treating physician. Within 72 hours of collection of the blood sample yielding the first positive blood culture, patients will be enrolled and randomised 1:1 to receive either adjunctive linezolid (600 mg orally two times per day for 5 days) or placebo. To determine patient-relevant outcomes, we implemented a comprehensive patient-representative consultation process. Consequently, we will use the desirability of outcome ranking (DOOR) established for S. aureus bacteraemia as the primary outcome at 90 days. The hierarchical composite DOOR outcome includes the following four components, ranked from most to least important: (1) survival, (2) return to level of function before S. aureus infection, (3) complications leading to treatment changes and serious adverse reactions; and (4) hospital length of stay. This approach will allow us to analyse the win ratio, that is, whether patients receiving linezolid have a better DOOR rank compared to patients in the placebo group. We calculated a target sample size of 606 patients providing 90% power at a two-sided significance level of 0.05.Ethics and dissemination Ethical approval was received from the Ethics committee for Northern and Central Switzerland (BASEC number 2025-00655). Eligible patients will be informed about the study by the local study team and asked for written consent if they wish to participate. For patients unable to provide informed consent, an appropriate substitute (ie, a close relative or a physician not involved in the research project) may make decisions based on the presumed wishes and the best interest of the patient. The patient’s own consent will be obtained as soon as their condition permits. Results will be published in peer-reviewed journals and in laymen's terms through various channels (social media, Swiss national portal HumRes).Trial registration number NCT06958835.",
  "authors": [
    {
      "affiliations": [
        "Division of Infectious Diseases, University Hospital Basel, Basel, Switzerland",
        "Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland"
      ],
      "name": "Natalie Rose"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Nadine S Bernasconi"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Michaela Schumacher"
    },
    {
      "affiliations": [
        "Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland"
      ],
      "name": "Laura Werlen"
    },
    {
      "affiliations": [
        "Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland"
      ],
      "name": "David Büchel"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Maja Weisser"
    },
    {
      "affiliations": [
        "Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland",
        "Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Severin B Vogt"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Claraspital Basel, Basel, Switzerland"
      ],
      "name": "Elisabeth Wehrle-Wieland"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases and Infection Prevention, Cantonal Hospital Aarau, Aarau, Switzerland"
      ],
      "name": "Anna Conen"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, University Hospital Inselspital and University of Bern, Bern, Switzerland"
      ],
      "name": "Maria C Thurnheer"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, University Hospital Inselspital and University of Bern, Bern, Switzerland"
      ],
      "name": "Yonas Martin"
    },
    {
      "affiliations": [
        "Department of General Internal Medicine / Infectious Diseases, Hôpital du Jura, Delémont, Switzerland"
      ],
      "name": "Michèle Birrer"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Ente Ospedaliero Cantonale, Lugano, Switzerland"
      ],
      "name": "Marco Bongiovanni"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Infection Prevention and Travel Medicine, HOCH Health Ostschweiz, Cantonal Hospital St. Gallen, St. Gallen, Switzerland"
      ],
      "name": "Werner C Albrich"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Department of Medicine, Cantonal Hospital Winterthur, Winterthur, Switzerland"
      ],
      "name": "Urs Karrer"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases and Infection Prevention, Stadtspital Zürich, Zürich, Switzerland"
      ],
      "name": "Adrian Schibli"
    },
    {
      "affiliations": [
        "Infection Control Program and World Health Organization Collaborating Centre, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland"
      ],
      "name": "Stephan Harbarth"
    },
    {
      "affiliations": [
        "Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"
      ],
      "name": "Matthaios Papadimitriou-Olivgeris"
    },
    {
      "affiliations": [
        "CLEAR-Methods Center, Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland"
      ],
      "name": "Matthias Briel"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zürich, Switzerland"
      ],
      "name": "Barbara Hasse"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Nina Khanna"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Richard Kuehl"
    },
    {
      "affiliations": [
        "CLEAR-Methods Center, Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland"
      ],
      "name": "Benjamin Speich"
    }
  ],
  "title": "Linezolid in addition to standard antibiotic treatment for Staphylococcus aureus bacteraemia: study protocol for a randomised, placebo-controlled trial",
  "uid": "892349cc-83c2-5594-9a3e-81a5351d9b74"
}