Linezolid Plus Standard of Care (LIPS)

University Hospital Basel

Status: Begins enrollment in 3 months

Conditions: Staphylococcus Aureus Bloodstream Infections (BSI; Bacteremia)

Treatments: Drug: Placebo; Drug: Linezolid 600 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT06958835

2025-00655 am23Khanna3;

Details and patient eligibility

About

The aim of the study is to assess whether targeting virulence factors by administering linezolid in addition to standard antibiotic treatment improves outcomes in patients with Staphylococcus aureus bacteraemia.

Full description

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.

Enrollment: 606 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Staphyloccus aureus (S. aureus) grown from at least one blood culture
• Hospitalised at a participating centre
• ≥18 years old
• Written informed consent

Exclusion criteria

• Administration of the initial drug treatment not feasible within 72 hours since the collection of the first positive blood culture with S. aureus
• Documented history of positive blood cultures for S. aureus occurring between 72 hours and 180 days prior to the eligibility assessment
• Necrotising fasciitis
• Currently receiving linezolid or clindamycin
• Previous type 1 hypersensitivity reaction to linezolid
• Current severe thrombocytopenia (i.e. <30 x 10^9/L)
• Application of study drug not possible (per mouth or per gastric tube)
• Local treating team believes that death is imminent and inevitable
• Patient is receiving end of life care and antibiotic treatment is not considered appropriate
• Local treating team believes that participation in the study is not in the best interest of the patient

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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606 participants in 2 patient groups, including a placebo group

Linezolid

Experimental group

Description:

600mg twice a day for 5 days (in addition to the standard antibiotic treatment)

Treatment:

Drug: Linezolid 600 mg

Placebo

Placebo Comparator group

Description:

oral placebo tablets twice a day for 5 days (in addition to the standard antibiotic treatment)

Treatment:

Drug: Placebo