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NCT Number: NCT03671967

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

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.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

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

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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

  • 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.
  • BSI due to specific infections known at the time of randomization:
  • Endocarditis / endovascular infections
  • Osteomyelitis (not resected)
  • Central nervous system infections
  • Allergy to any of the study drugs confirmed by history taken by the investigator
  • Previous enrollment in this trial
  • Concurrent participation in another interventional clinical trial
  • Imminent death (researcher's assessment of expected death within 48 hrs. of recruitment)

Treatment and study plan

Piperacillin/tazobactam

Drug

4.5 grams QID

Meropenem

Drug

1 gram TID

Primary outcomes

  1. All-cause mortality

    Time frame: 30 days from randomization

  2. Treatment failure

    Time frame: 7 days from randomization

    death OR fever > 38°C in the last 48 hours OR lack of resolution of symptoms attributed to the focus of infection OR Sequential Failure Organ Assessment (SOFA) score increasing OR positive blood cultures by the time point assessed

Secondary outcomes

  1. All-cause mortality

    Time frame: 14 and 90 days from randomization

  2. Treatment failure

    Time frame: 14 days and 30 days from randomization

    death OR fever > 38°C in the last 48 hours OR lack of resolution of symptoms attributed to the focus of infection OR Sequential Failure Organ Assessment (SOFA) score increasing OR positive blood cultures by the time point assessed

  3. Microbiological failure

    Time frame: 7 days and 14 days from randomization

    Repeat positive blood cultures with index pathogen on day 4 or later from randomization

  4. Recurrent positive blood cultures (relapse)

    Time frame: 30 days and 90 days from randomization

    recurrent positive blood cultures with the index pathogen after prior sterilization of blood cultures or after end of treatment

  5. Clostridium difficile associated diarrhea

    Time frame: 90 days from randomization

  6. Clinically or microbiologically documented infection other than Gram-negative bacteremia

    Time frame: 90 days from randomization

  7. Number of hospital re-admissions

    Time frame: 90 days from randomization

  8. Development of resistance

    Time frame: 90 days from randomization

    clinical isolates resistant to piperacillin/tazobactam and meropenem and any carbapenem-resistant bacteria

  9. Carriage of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae in-hospital

    Time frame: 90 days from randomization

    detected by weekly rectal surveillance of carriage while in-hospital

  10. Total in-hospital days

    Time frame: 30 days and 90 days from randomization

  11. Total antibiotic days

    Time frame: 30 days and 90 days from randomization

  12. Adverse events

    Time frame: 30 days from randomization

    diarrhea, liver function test abnormalities, antibiotic rash or other immediate-type allergy, acute kidney injury defined according to RIFLE criteria

Study contacts

Contact information is provided by the study sponsor or research team.

Mical Paul, MD

CONTACT

[email protected]

972-4-7772991

Roni Bitterman, MD

CONTACT

[email protected]

972-4-7772991

Sponsors and collaborators

Lead sponsor

Rambam Health Care Campus

Other

Collaborators

  • Canadian Institutes of Health Research (CIHR)
  • Hadassah Medical Organization
  • Jewish General Hospital
  • McGill University Health Centre/Research Institute of the McGill University Health Centre
  • Meir Medical Center
  • Rabin Medical Center
  • Soroka University Medical Center
  • Tel Aviv Medical Center
  • The Chaim Sheba Medical Center
  • University of Modena and Reggio Emilia

Registry information

Official study title

Piperacillin Tazobactam Versus Meropenem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae- a Non-inferiority Randomized Controlled Trial

Acronym: PETERPEN

Important dates

Study start
2019
Primary completion
2027
Study completion
2027
First posted
Sep 14, 2018
Registry last updated
Aug 1, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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