Recruiting

PipEracillin & MERoPENem

Sponsor:

Rambam Health Care Campus

Code:

NCT03671967

Conditions

Beta Lactam Resistant Bacterial Infection

Enterobacteriaceae Infections

Bacteremia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Piperacillin/tazobactam

Meropenem

Study Details

Brief summary:

Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae blood-stream infection are lacking. Observational studies show conflicting results when comparing treatment with combination beta-lactam-beta-lactamase inhibitor and carbapenems. The investigators aim to evaluate the effect of definitive treatment with meropenem vs. piperacillin-tazobactam on the outcome of patients with bacteremia due to cephalosporin-non-susceptible Enterobacteriaceae. The investigators hypothesize that piperacillin-tazobactam is non-inferior to meropenem.

Conditions

Beta Lactam Resistant Bacterial Infection

Enterobacteriaceae Infections

Bacteremia

Study ID

NCT03671967

Start date

May 1, 2019

Status verified date

Jul, 2025

Completion date

Apr 1, 2027

Anticipated

Primary completion date

Jan 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

1084 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: piperacillin tazobactam

active comparator: meropenem

Interventions

Piperacillin/tazobactam

4.5 grams QID

Meropenem

1 gram TID

Primary outcome measure

  • All-cause mortality [ Time Frame: 30 days from randomization ]
  • Treatment failure [ Time Frame: 7 days from randomization ]

Central Contacts and Locations

Locations

University of Calgary, Cumming School of Medicine, O'Brien Institute for Public Health

Recruiting

Calgary, Alberta, Canada, T2N 4Z6

Contacts

John Conly, MD

jconly@ucalgary.ca

Principal Investigator:

John Conly, MD

Surrey Memorial Hospital - Fraser Health Authority

Recruiting

Surrey, British Columbia, Canada

Contacts

Principal Investigator:

Kevin Afra, MD

Eastern Health

Recruiting

St. John's, Newfoundland and Labrador, Canada

Contacts

Peter Daley, MD

pkd336@mun.ca

Principal Investigator:

Peter Daley, MD

Kingston General Hospital

Recruiting

Kingston, Ontario, Canada

Contacts

Barbara Antuna Puente, MD

Barbarbara.antunapuente@queensu.ca

Jewish Genral Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Contacts

McGill University Health Centre

Recruiting

Montreal, Quebec, Canada

Contacts

Principal Investigator:

Todd Lee, MD

More Information

Sponsor

Rambam Health Care Campus

Last update posted

Aug 1, 2025

Last verified

Jul, 2025

Keywords

  • bacteremia
  • enterobacteriaceae
  • extended spectrum beta-lactamase
  • meropenem
  • piperacillin tazobactam

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Rambam Health Care Campus on 2025-08-01.