Ceftolozane-tazobactam Versus Meropenem for ESBL and AmpC-producing Enterobacterales Bloodstream Infection

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether ceftolozane-tazobactam is as effective as meropenem with respect to 30 day mortality in the treatment of bloodstream infection due to third-generation cephalosporin non-susceptible Enterobacterales or a known chromosomal AmpC-producing Enterobacterales (Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Queensland
• Collaborators: Merck Sharp & Dohme (Australia) Pty Limited; Merck Sharp & Dohme Corp.
• Treatments: Ceftolozane; Ceftolozane, tazobactam drug combination; Cephalosporins; Meropenem; Penicillanic Acid; Tazobactam

Criteria

Inclusion Criteria:

• Bloodstream infection defined as presence in at least one peripheral blood culture draw demonstrating Enterobacterales with proven non-susceptibility to third generation cephalosporins or cephalosporin susceptible species known to harbour chromosomal AmpC-beta-lactamases (Enterobacter spp., Klebsiella aerogenes, Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens) during hospitalisation

• Patient is aged 18 years and over (21 and over in Singapore)

• The patient or approved proxy is able to provide informed consent

• ≤72 hours has elapsed since the first positive qualifying (index) blood culture collection

• Expected to receive IV therapy for ≥5 days

Exclusion Criteria:

• Known hypersensitivity to a cephalosporin or a carbapenem, or anaphylaxis to beta-lactam antibiotics

• Participant with significant polymicrobial bloodstream infection (i.e. not a contaminant)

• Treatment is not with the intent to cure the infection (i.e. palliative intent) or the expected survival is ≤4 days

• Participant is pregnant or breast-feeding (tested for in women of child-bearing age only)

• Use of concomitant antimicrobials with known activity against Gram-negative bacilli (except trimethoprim/sulfamethoxazole for Pneumocystis prophylaxis and when adding metronidazole for suspected IAI) in the first 5 days post-randomisation

• Participant with CrCl <15 mL/minute or on renal replacement therapy (in addition, participants will be withdrawn from the study if CrCl reaches this level)

• Previously randomised in the MERINO-3 trial or concurrently enrolled in another therapeutic antibiotic clinical trial

• Blood culture isolate with in-vitro resistance to either meropenem or ceftolozane-tazobactam (known either at time of enrolment or during the course of study treatment, in which case the participant will be withdrawn)