Combination Cefazolin with Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia

Launched by TODD C. LEE MD MPH FIDSA · May 10, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating whether combining two antibiotics, cefazolin and ertapenem, can improve treatment outcomes for patients with a type of blood infection caused by methicillin-susceptible Staphylococcus aureus (MSSA). Previous research has suggested that this combination might be more effective than using cefazolin alone, but this is the first time it is being tested in a randomized controlled trial setting.

To participate in this study, you need to be at least 18 years old and have been diagnosed with an MSSA blood infection within the last 48 hours. Eligible participants will be receiving cefazolin or will be switched to it based on their doctor’s recommendation. The trial is currently recruiting participants and aims to enroll patients quickly after their infection is identified. If you decide to participate, you will receive the combination treatment as part of your care, and your progress will be monitored closely by the research team. It's important to note that certain conditions, such as severe allergic reactions to specific antibiotics or critical health issues, may exclude you from participating.

Gender

ALL

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.