ClinicalTrials.gg
Sign In
RecruitingNCT03671967PETERPENUpdated Aug 1, 2025

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

A Phase 4 interventional study of Piperacillin/tazobactam and Meropenem in Beta Lactam Resistant Bacterial Infection, Enterobacteriaceae Infections and Bacteremia, sponsored by Rambam Health Care Campus. Recruiting at 14 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-01.

Sponsored by Rambam Health Care Campus · Phase 4, Interventional, and Treatment

From the registry’s dates

  • Started May 2019; still recruiting 7 years 6 months later.
Phase
Phase 4
Study type
Interventional
Enrollment
1,084
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Beta Lactam Resistant Bacterial Infection
  • Enterobacteriaceae Infections
  • Bacteremia

Keywords

  • bacteremia
  • enterobacteriaceae
  • extended spectrum beta-lactamase
  • meropenem
  • piperacillin tazobactam
03

In context

Enterobacteriaceae Infections

59 studies on the registry are indexed under Enterobacteriaceae Infections; 14 are open to participants now.

This study's planned enrollment of 1,084 is above the median of 99 across 27 interventional studies indexed under Enterobacteriaceae Infections.

Browse Enterobacteriaceae Infections studies →

Lead sponsor

Rambam Health Care Campus is the lead sponsor of 466 studies on the registry; 34 are open to participants now.

Browse Rambam Health Care Campus studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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)
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,084 participants (estimated)

Study arms

  • Experimental
    piperacillin tazobactam

    Drug: Piperacillin/tazobactam

  • Active comparator
    meropenem

    Drug: Meropenem

Interventions

  • DrugPiperacillin/tazobactam

    4.5 grams QID

  • DrugMeropenem

    1 gram TID

06

What researchers measure

Primary outcomes

  1. All-cause mortality

    Time frame: 30 days from randomization

  2. Treatment failure

    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

    Time frame: 7 days from randomization

Secondary outcomes

  1. All-cause mortality

    Time frame: 14 and 90 days from randomization

  2. Treatment failure

    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

    Time frame: 14 days and 30 days from randomization

  3. Microbiological failure

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

    Time frame: 7 days and 14 days from randomization

  4. Recurrent positive blood cultures (relapse)

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

    Time frame: 30 days and 90 days from randomization

  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

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

    Time frame: 90 days from randomization

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

    detected by weekly rectal surveillance of carriage while in-hospital

    Time frame: 90 days from randomization

  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

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

    Time frame: 30 days from randomization

07

Study locations

14 of 14 sites recruiting
08

References and documents

Publications

  • Bitterman R, Koppel F, Mussini C, Geffen Y, Chowers M, Rahav G, Nesher L, Ben-Ami R, Turjeman A, Huberman Samuel M, Cheng MP, Lee TC, Leibovici L, Yahav D, Paul M. Piperacillin-tazobactam versus meropenem for treatment of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacteriaceae: a study protocol for a non-inferiority open-label randomised controlled trial (PeterPen). BMJ Open. 2021 Feb 8;11(2):e040210. doi: 10.1136/bmjopen-2020-040210. PubMed 33558347 ↗

Individual participant data

Plan to share: Yes — De-identified individual patient data collected during the trial will be made available for an unlimited time period following publication of trial results. Data will be available for researchers who provide a methodologically sound proposal and contingent on both the researchers' and our ethics committee approval and the signing of a data sharing agreement.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code

Time frame: following publication and for unlimited time

Access criteria: proposals should be sent to the principal investigator at ro_oren@rambam.health.gov.il

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 1, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03671967
Lead sponsor
Rambam Health Care Campus
Collaborators
Rabin Medical Center, University of Modena and Reggio Emilia, Tel Aviv Medical Center, Meir Medical Center, Soroka University Medical Center, The Chaim Sheba Medical Center, McGill University Health Centre/Research Institute of the McGill University Health Centre, Jewish General Hospital, Canadian Institutes of Health Research (CIHR), Hadassah Medical Organization
Responsible party
Sponsor
First posted
Sep 14, 2018
Start date
May 1, 2019
Primary completion
Jan 1, 2027 (estimated)
Completion
Apr 1, 2027 (estimated)
Last update
Aug 1, 2025

Study contacts

Mical Paul, MD
Contact
m_paul@rambam.health.gov.il
972-4-7772991
Roni Bitterman, MD
Contact
ro_oren@rambam.health.gov.il
972-4-7772991
Roni Bitterman, MD
principal investigator · Rambam Health Care Campus
Mical Paul, MD
study director · Rambam Health Care Campus
Leonard Leibovici, MD
study director · Rabin Medical Center
Cristina Mussini, MD
study director · University of Modena and Reggio Emilia
Noa Eliakim-Raz, MD
study director · Rabin Medical Center, Beilinson Campus

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Enterobacteriaceae Infections →

Other studies from this sponsor

Rambam Health Care Campus →

Start the discussion