Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia (CERT)
Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Septicemia, Staphylococcal Sepsis
About this trial
This is an interventional treatment trial for Staphylococcus Aureus Bacteremia focused on measuring Staphylococcus aureus, Methicillin-susceptible, Bacteremia
Eligibility Criteria
Inclusion Criteria:
- Adult >=18 years old
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
- 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:
- At time of recruitment, the patient has already clinically improved with at least one subsequent negative culture at >24 hours incubation
- Anaphylaxis to any beta-lactam antibiotic (and any allergy to ertapenem) Polymicrobial bacteremia (not including skin commensals)
- Known seizure disorder
- Any receipt of valproic acid
- Expected mortality within 48 hours
- Need for critical care resources but "do not resuscitate" status precludes the receipt of critical care
- Unable to provide informed consent and no available healthcare proxy (with ethics approval for deferred consent in cases of severe illness)
Administrative:
- Refusal to provide informed consent
- Refusal of healthcare team to participate
- No reliable means of outpatient contact (telephone/email/text)
- Previously enrolled
- 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.
Sites / Locations
- McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital)
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Ertapenem
Placebo
Ertapenem 1g IV daily infused over 2 hours x 5 days
Saline placebo infused daily over 2 hours x 5 days