PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)

Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorRambam Health Care Campus

About this trial

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.

Eligibility criteria

Qualifiers

Adults (age ≥ 18 years)

New onset BSI due to E. coli or Klebsiella spp. in one or more blood cultures associated with evidence of infection.

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).

Both community and hospital-acquired bacteremias will be included.

Disqualifiers

More than 72 hr. elapsed since initial blood culture taken, regardless of the time covering antibiotics were started (up to 72 hrs.).

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.

Patients with prior bacteremia or infection that have not completed antimicrobial therapy for the previous infectious episode.

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.

Trial design

Treatments tested in this trial

  • Piperacillin/tazobactam
  • Meropenem

Treatment groups

1,084 Participants
are divided into 2 treatment groups

Sponsors and collaborators

Rambam Health Care Campus

Lead sponsor

Rabin Medical Center

Collaborator

University of Modena and Reggio Emilia

Collaborator

Tel Aviv Medical Center

Collaborator

Meir Medical Center

Collaborator

Soroka University Medical Center

Collaborator

The Chaim Sheba Medical Center

Collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Jewish General Hospital

Collaborator

Canadian Institutes of Health Research (CIHR)

Collaborator

Hadassah Medical Organization

Collaborator