Non-inferiority Trial Comparing Cloxacillin vs Cefazolin in Methicillin-susceptible Staphylococcus Aureus Bacteremia

• Status: Recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: All

Summary

"Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia remains a major cause of community- or hospital-acquired bloodstream infections with an overall mortality estimated around 25%. Anti-staphylococcal penicillins (APs) such as oxacillin or cloxacillin are recommended as first-line agents. With the exception of first-generation cephalosporin (1GC) such as cefazolin, no alternative has yet proven a similar efficacy. Due to an unfavourable safety profile for high doses used in severe infection, an uneasy dosing schedule in patients with renal failure and possible recurrent stock-out events for APs, alternative to APs are needed. This led to propose an open-label, randomized, controlled parallel groups, phase IV, non-inferiority trial comparing the efficacy, the safety, and the ecological impact of cefazolin versus cloxacillin for the treatment of MSSA bacteremia in adults.

The primary objective is to compare the therapeutic efficacy of cefazolin vs cloxacillin at day 90 after the inclusion. "

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Cefazolin; Cloxacillin; Methicillin

Criteria

Inclusion Criteria:

1. Age above 18 years

2. Blood culture positive to MSSA identified by standard bacteriologic techniques or by GeneXpert PCR

Exclusion Criteria:

1. Previous type 1 or grade 3 - 4 according to CTCAE hypersensitivity reaction to beta-lactams

2. Known pregnancy or breastfeeding women

3. Parenteral antimicrobial therapy active against MSSA for more than 72 hours after the positive SA blood culture ponction

4. Chronic renal failure defined by a glomerular filtration rate estimated < 30 mL/min/1,73m².

5. Presence of an intra-vascular implant (vascular or valvular prosthesis or cardiovascular implantable electronic device)

6. Patient with implanted material considered to be infected by SAMS and whose antibiotic treatment is longer than 70 days

7. New cerebro-spinal signs in the preceding month

8. Clinical examination compatible with recent stroke (<1 month), brain abscess or meningitis

9. Current other antibiotic therapy which cannot be ceased or substituted by study treatment

10. Mixed blood culture with more than one pathogen (excluding contaminants:

Corynebacterium sp., Propionibacterium sp., Coagulase-Negative Staphylococci)

11. coagulapthy with TP< 50% (excepted for patients under avk anticoagulant treatment)

12. Absence of written informed consent from the patient

13. Limitation of care with expected life duration below 90 days

14. Patient under guardianship or trusteeship

15. No affiliation to social security (beneficiary or assignee)

16. Subject already involved in another interventional clinical research evaluating a medicinal product

Secondary exclusion criteria:

1. Diagnosis of meningitis made after randomisation

2. Diagnosis of brain abscess made after randomisation

3. Diagnosis of multiple infection made after randomisation