Cefazolin is licenced in Canada for the management of infections due to susceptible Staphylococcus aureus, including bacteremia. It has been commonly used for decades in this disease and, when compared in observational studies to anti-staphylococcal penicillins, has demonstrated reduced mortality.

Nevertheless, in the treatment of methicillin-susceptible S. aureus (MSSA) bacteremia, there remains significant opportunities to improve clinical outcomes. Indeed, S. aureus bacteremia kills more Canadians annually than myeloma, melanoma, renal, ovarian or stomach cancers. Overall mortality approached 18% in a recent Canadian clinical trial performed by our group. The duration of bacteremia, particularly after antibiotherapy is recognized as a major risk factor for mortality. Interventions which reduce the duration of bacteremia, without increasing the frequency of renal failure like gentamicin did, are among the most promising candidates for larger phase 3 studies designed to impact patient mortality.

Ertapenem is a commonly used antibiotic which has been on the Canadian market for more than 15 years. It is most commonly used in patients with infections caused by extended-spectrum beta-lactamase producing Enterobacteraciae; however, it has a broad spectrum of activity including Gram-positive bacteria such as S. aureus. Indeed, the drug is licenced in Canada for the treatment of complicated skin and soft tissue infections commonly caused by S. aureus.

The study population will be adult patients presenting with MSSA bacteremia.

Inclusion Criteria:

1. Adult >=18 years old

‍2. S. aureus bacteremia within the past 48 hours: a) with any unknown MRSA status (in centres with <15% prevalence of MRSA in their annual blood cultures) or known negative MRSA screening swab within 90 days or b) which has already been shown to be MSSA by the approved laboratory policy

3. Current receipt of cefazolin monotherapy or clinically appropriate (according to treating ID specialist) to switch to cefazolin monotherapy as the backbone therapy (open label, non-study drug). 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 prior to final identification.

‍

Exclusion Criteria: 

Clinical:

1. At the time of screening, patient has already clinically improved with at least one subsequent negative culture at >24 hours incubation
2. Hypersensitivity/anaphylaxis to any beta-lactam antibiotic (and any allergy to ertapenem) or component of the formulation
3. Polymicrobial bacteremia (not including skin commensals) defined as more than one organism [at species level] in blood cultures reported between collection of the index blood culture and eligibility assessment, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician.
4. Known seizure disorder
5. Any receipt of valproic acid
6. Expected mortality within 48 hours according to treating team
7. Need for critical care resources but “do not resuscitate” status precludes ICU admission
8. Refusal of healthcare team to participate
9. Known positive blood culture for S. aureus (PSSA/MSSA) between 72 hours and 180 days prior to the time of eligibility assessment
10. Patient has died since the collection of the index blood culture
11. Patient is receiving palliative care where antibiotic treatment is not appropriate.

Administrative:

1. No reliable means of outpatient contact (telephone/email/text)
2. Previously enrolled
3. Patients whose isolate is identified as MRSA post-enrollment will be subsequently excluded (see below).
4. Unable to provide informed consent and no available healthcare proxy (where ethics approval has not been obtained for deferred consent or patient is not eligible for deferred consent)
5. Refusal to provide informed consent

We will compare the addition of ertapenem 1g IV DIE given as a 2-hour infusion (with renal adjustment) or placebo to a backbone of cefazolin therapy in MSSA bacteremia.

The duration of therapy will be the shortest of: death, discharge from hospital, clinical success on 2 consecutive days, or 5 total days of therapy.

For anyquestions about this analysis, please reach out using the contact detailsbelow.

Name: A/Prof Todd C Lee

Institution: McGill University, Canada

Email: todd.lee@mcgill.ca

This nested trial is registered on ClinicalTrials.gov: NCT04886284