RecruitingPhase 2NCT04886284

Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia

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

Sponsor

Todd C. Lee MD MPH FIDSA

Enrollment

60 participants

Start Date

May 20, 2024

Study Type

INTERVENTIONAL

Conditions

Staphylococcus Aureus Bacteremia Staphylococcus Aureus Endocarditis Staphylococcus Aureus Septicemia Staphylococcal Sepsis

Summary

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)

Eligibility

Min Age: 18 YearsMax Age: 100 Years

Inclusion Criteria6

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 Criteria15

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.