Comparing two antibiotics for treating bloodstream infections from resistant bacteria
Piperacillin Tazobactam Versus Meropenem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae- a Non-inferiority Randomized Controlled Trial
This study is testing if a new antibiotic called piperacillin-tazobactam works as well as meropenem for treating bloodstream infections caused by resistant bacteria in adults.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 1084 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Rambam Health Care Campus Academic / other |
| Locations | 14 sites (Calgary, Alberta and 13 other locations) |
| Trial ID | NCT03671967 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the effectiveness of piperacillin-tazobactam compared to meropenem in treating bloodstream infections caused by cephalosporin-resistant Enterobacteriaceae. The study focuses on adult patients with new onset bacteremia due to E. coli or Klebsiella spp. and aims to determine if piperacillin-tazobactam is as effective as meropenem. Participants will be monitored for treatment outcomes to assess the non-inferiority of piperacillin-tazobactam. The trial includes both community and hospital-acquired infections.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with bloodstream infections caused by E. coli or Klebsiella spp. that are resistant to third-generation cephalosporins.
Not a fit: Patients with polymicrobial bacteremia or those who have had more than 72 hours since their initial blood culture may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide an effective alternative treatment option for patients with resistant bacterial infections.
How similar studies have performed: Other studies have shown mixed results when comparing similar antibiotic treatments, making this approach both relevant and necessary.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Adults (age ≥ 18 years) 2. New onset BSI due to E. coli or Klebsiella spp. in one or more blood cultures associated with evidence of infection. 3. The microorganism will have to be non-susceptible to third generation cephalosporins (ceftriaxone and ceftazidime) and susceptible to both PTZ and meropenem (see microbiological methods). 4. Both community and hospital-acquired bacteremias will be included. 5. We will permit the inclusion of bacteremias due to E. coli or Klebsiella spp. with concomitant growth in blood of skin commensals considered as contaminants. Exclusion Criteria: 1. More than 72 hr. elapsed since initial blood culture taken, regardless of the time covering antibiotics were started (up to 72 hrs.). 2. Polymicrobial bacteremia. Polymicrobial bacteremia will be defined as either growth of two or more different species of microorganisms in the same blood culture, or growth of different species in two or more separate blood cultures within the same episode. 3. Patients with prior bacteremia or infection that have not completed antimicrobial therapy for the previous infectious episode. 4. Patients with septic shock at the time of enrollment and randomization, defined as at least 2 measurements of systolic blood pressure \< 90 mmHg and/or use of vasopressors (dopamine\>15μg/kg/min, adrenalin\>0.1μg/kg/min, noradrenalin\>0.1μg/kg/min, vasopressin any dose) in the 12 hours prior to randomization. In the absence of the use of vasopressors, a systolic blood pressure \<90 would need to represent a deviation for the patient's known normal blood pressure. 5. BSI due to specific infections known at the time of randomization: 1. Endocarditis / endovascular infections 2. Osteomyelitis (not resected) 3. Central nervous system infections 6. Allergy to any of the study drugs confirmed by history taken by the investigator 7. Previous enrollment in this trial 8. Concurrent participation in another interventional clinical trial 9. Imminent death (researcher's assessment of expected death within 48 hrs. of recruitment)
Where this trial is running
Calgary, Alberta and 13 other locations
- University of Calgary, Cumming School of Medicine, O'Brien Institute for Public Health — Calgary, Alberta, Canada (Recruiting)
- Surrey Memorial Hospital - Fraser Health Authority — Surrey, British Columbia, Canada (Recruiting)
- Eastern Health — St. John's, Newfoundland and Labrador, Canada (Recruiting)
- Kingston General Hospital — Kingston, Ontario, Canada (Recruiting)
- Jewish Genral Hospital — Montreal, Quebec, Canada (Recruiting)
- McGill University Health Centre — Montreal, Quebec, Canada (Recruiting)
- Rambam Health Care Campus — Haifa, Israel, Israel (Recruiting)
- Soroka Medical Center — Beersheba, Israel (Recruiting)
- Hadassah Medical Center — Jerusalem, Israel (Recruiting)
- Meir Medical Center — Kfar Saba, Israel (Recruiting)
- Sanz Medical Center-Laniado Hospital — Netanya, Israel (Recruiting)
- Rabin Medical Center, Beilinson Campus — Petah Tikva, Israel (Recruiting)
- Sheba Medical Center (Tel HaShomer) — Tel Aviv, Israel (Recruiting)
- Sourasky Medical Center — Tel Aviv, Israel (Recruiting)
Study contacts
- Principal investigator: Roni Bitterman, MD — Rambam Health Care Campus
- Study coordinator: Mical Paul, MD
- Email: m_paul@rambam.health.gov.il
- Phone: 972-4-7772991
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.