Combining two antibiotics to treat Staphylococcus aureus bacteremia

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial investigates the effectiveness of combining cefazolin with ertapenem for treating methicillin-susceptible Staphylococcus aureus bacteremia. The study aims to determine if this combination can reduce the duration of bacteremia and improve patient outcomes compared to standard treatment. Participants must be adults diagnosed with S. aureus bacteremia within the last 48 hours and currently receiving cefazolin. The trial is part of a larger adaptive platform study focused on improving treatment for S. aureus infections.

Why it matters

Who can join: the full rules

The participant must fulfil all inclusion and exclusion criteria for the SNAP Platform (NCT05137119) and also the following inclusion and exclusion criteria to be eligible for this sub-study:

Inclusion Criteria:

1. Adult \>=18 years old
2. S. aureus bacteremia within the past 48 hours:

   * with any unknown MRSA status (in centers with \<15% prevalence of MRSA in their annual blood cultures) or known negative MRSA screening swab within 90 days OR
   * which has already been shown to be MSSA
3. Current receipt of cefazolin or where it would be clinically appropriate (according to treating ID specialist) to switch to cefazolin as the backbone therapy (open label, non-study drug).

NOTE: Up to an additional 12-24 hours of open label non-study VANCOMYCIN, LINEZOLID or DAPTOMYCIN may be allowed if there is sepsis and clinical concern for MRSA has not been excluded.

Exclusion Criteria:

Clinical:

1. At time of recruitment, the patient has already clinically improved with at least one subsequent negative culture at \>24 hours incubation
2. Anaphylaxis to any beta-lactam antibiotic (and any allergy to ertapenem) Polymicrobial bacteremia (not including skin commensals)
3. Known seizure disorder
4. Any receipt of valproic acid
5. Expected mortality within 48 hours
6. Need for critical care resources but "do not resuscitate" status precludes the receipt of critical care
7. Unable to provide informed consent and no available healthcare proxy (with ethics approval for deferred consent in cases of severe illness)

Administrative:

1. Refusal to provide informed consent
2. Refusal of healthcare team to participate
3. No reliable means of outpatient contact (telephone/email/text)
4. Previously enrolled
5. Patients whose isolate is identified as MRSA post-enrollment will be subsequently excluded (see below).

Note that because MSSA is much more common than MRSA in Canada (90% of all S. aureus bacteremia at MUHC, for example, are MSSA and in the presence of a negative MRSA screening swab or unknown MRSA status, this means that the risk of MRSA is less than 5%). We believe time to combination therapy is likely linked to benefit, therefore we will recruit the patients as soon as S. aureus is identified but potentially prior to confirmation the organism is MSSA. Where possible, rapid MRSA detection techniques will be deployed; however with conventional screening this will mean approximately a 12-24 hours delay. Organisms subsequently identified as MRSA will be excluded from the intention to treat analysis and the sample size will be adjusted accordingly to ensure the total enrollment meets study goals.

Where it's running

• Foothills Medical Centre
  Calgary, Alberta, Canada Recruiting
• Surrey Memorial Hospital
  Surrey, British Columbia, Canada Recruiting
• Hamilton Health Sciences (Hamilton General Hospital and Juravinski Hospital)
  Hamilton, Ontario, Canada Recruiting
• The Ottawa Hospital - General Campus
  Ottawa, Ontario, Canada Recruiting
• Niagara Health - St. Catharines site
  Saint Catharines, Ontario, Canada Recruiting
• Hospital de la Cité de la Sante
  Laval, Quebec, Canada Recruiting

Study contacts

• Principal investigator: Todd C Lee, MD MPH FIDSA — Research Institute of the McGill University Health Centre
• Study coordinator: Lina Petrella
• Email: lina.petrella@muhc.mcgill.ca
• Phone: 514-934-1934

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Switching to dabigatran versus staying on apixaban/edoxaban/rivaroxaban for S. aureus bloodstream infection

  This trial will try whether switching people with S. aureus bloodstream infection who are already taking apixaban, edoxaban, or rivaroxaban to dabigatran leads to better outcomes.

  Recruiting at 3 sites Phase 4 McGill University Health Centre/Research Institute of the McGill University Health Centre · St. John's, Newfoundland and Labrador and 2 other locations · NCT06650501

• Comparing Daptomycin and Vancomycin for MRSA Bloodstream Infections

  This study is testing whether daptomycin or vancomycin works better for treating bloodstream infections caused by MRSA in patients.

  Recruiting at 20 sites Phase 4 McGill University Health Centre/Research Institute of the McGill University Health Centre · Blacktown, New South Wales and 19 other locations · NCT06637332

• Clopidogrel versus aspirin to lower cardiovascular and infection complications in people with Staphylococcus aureus bloodstream infection

  This will try switching people with Staphylococcus aureus bloodstream infection who are already taking aspirin for heart protection to clopidogrel to see if it improves infection outcomes.

  Recruiting at 3 sites Phase 4 McGill University Health Centre/Research Institute of the McGill University Health Centre · St. John's, Newfoundland and Labrador and 2 other locations · NCT06650488

• Combination Antibiotics for Staphylococcus aureus Bacteremia in adults

  This study tests whether using two antibiotics together for adults with Staphylococcus aureus in the blood works better than a single antibiotic.

  Recruiting at 13 sites Phase 4 Intermountain Health Care, Inc. · Brighton, Colorado and 12 other locations · NCT07376889

• Evaluating treatments for Staphylococcus aureus bloodstream infections

  This study is testing different treatments for people with Staphylococcus aureus bloodstream infections to find out which ones work best to help them recover and live longer.

  Recruiting at 126 sites Phase 4 University of Melbourne · Houston, Texas and 160 other locations · NCT05137119

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.