Linezolid Plus Standard of Care

Staphylococcus aureus (S. aureus) is one of the deadliest bacterial pathogens, especially in high-income countries, and causes bloodstream infections (bacteraemia) in 20-30 per 100,000 people annually. Despite widely available antibiotic treatments, the 90-day mortality rate remains high at 20-30%, and complications such as organ damage, relapses, and long-term impairment affect many survivors. Existing treatments have failed to improve survival rates highlighting the urgent need for novel therapeutic strategies.

Virulence factors produced by S. aureus facilitate bacterial persistence and spread, and tissue damage. Preclinical research suggests that inhibiting the production of virulence factors may improve patient outcomes. While some clinical guidelines recommend this approach for toxin-mediated infections, randomized controlled trials (RCTs) evaluating this approach in S. aureus bacteraemia have not yet been conducted.

Linezolid, an antibiotic commonly used for pneumonia and complicated skin and soft-tissue infections, has shown strong inhibition of the expression of S. aureus virulence factors in preclinical studies. Studies in animal models demonstrated that linezolid, when combined with other antibiotics, enhances treatment efficacy and reduces bacterial toxin production. Observational studies suggest that early initiation of linezolid may lead to better patient outcomes, but no RCT has tested this approach in S. aureus bacteraemia.

This placebo-controlled trial will evaluate whether adding a 5-day course of linezolid to standard antibiotic therapy improves clinical outcomes in patients with S. aureus bacteraemia.

• All-cause mortality [Срок оценки: From randomisation (day 1) until day 90]
• Time to death [Срок оценки: From randomisation (day 1) until day 90]
• Level of function [Срок оценки: From randomisation (day 1) until day 90]
• Number of participants with microbiological failure leading to treatment change [Срок оценки: From day 14 to day 90 (randomisation = day 1)]
• Number of participants with early microbiological failure leading to treatment change [Срок оценки: From day 5 to day 13 (randomisation = day 1)]
• Number of participants with clinical failure leading to treatment change [Срок оценки: From day 14 to day 90 (randomisation = day 1)]
• Number of participants with early clinical failure leading to treatment change [Срок оценки: From day 5 to day 13 (randomisation = day 1)]
• Hospital length of stay [Срок оценки: From randomisation (day 1) until day 90]
• Time to being discharged alive [Срок оценки: From randomisation (day 1) until day 90]
• Days alive without being on the Intensive Care Unit (ICU) [Срок оценки: From randomisation (day 1) until day 90]
• Days alive without antibiotics [Срок оценки: From randomisation (day 1) until day 90]
• Mental health [Срок оценки: At day 90 (randomisation = day 1)]