Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia

There is a variety of in vitro, in vivo (animal model), and human case series data which suggests that the addition of ertapenem to cefazolin could improve outcomes in methicillin-susceptible S. aureus bacteremia. No randomized controlled trial has been performed. This study is an approved sub-study of The Staphylococcus aureus Network Adaptive Platform (SNAP) trial (NCT05137119)

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 \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.