Combining two antibiotics to treat Staphylococcus aureus bacteremia

Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia (CERT)

This study is testing if using two antibiotics together can help adults with Staphylococcus aureus bacteremia get better faster than the usual treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (Academic / other)
• Locations: 5 sites (Calgary, Alberta and 4 other locations)
• Trial ID: NCT04886284 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with recent methicillin-susceptible S. aureus bacteremia.

Not a fit: Patients who have already shown clinical improvement or have a known MRSA infection may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce mortality rates associated with S. aureus bacteremia.

How similar studies have performed: While there is no prior randomized controlled trial for this specific combination, existing observational data suggests potential benefits, indicating this approach is promising yet novel.

Eligibility criteria

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 this trial is running

Calgary, Alberta and 4 other locations

• Foothills Medical Centre — Calgary, Alberta, Canada (Recruiting)
• Hamilton Health Sciences (Hamilton General Hospital and Juravinski Hospital) — Hamilton, Ontario, Canada (Recruiting)
• Niagara Health - St. Catharines site — Saint Catharines, Ontario, Canada (Recruiting)
• Hospital de la Cité de la Sante — Laval, Quebec, Canada (Recruiting)
• McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital) — Montreal, 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

Conditions Staphylococcus Aureus Bacteremia; Staphylococcus Aureus Septicemia; Staphylococcal Sepsis; Staphylococcus Aureus Endocarditis; Staphylococcus aureus; Methicillin-susceptible; Bacteremia