Beta Lactam Resistant Bacterial InfectionPhase 4SPICE-MNCT05355350

PipEracillin/Tazobactam Versus mERoPENem for Treatment of AmpC Producing Blood Stream Infections

A Phase 4 study testing Piperacillin / Tazobactam Injection and Meropenem in people with Beta Lactam Resistant Bacterial Infection and Enterobacteriaceae Infections, run by Rambam Health Care Campus at 4 sites in Israel.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 to 120 years
Conditions the study is for: Beta Lactam Resistant Bacterial Infection, Enterobacteriaceae Infections, Bacteremia
What is being tested?: Piperacillin / Tazobactam Injection and Meropenem
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 4 sitesIsrael
Study dates: 1 Jul 2022to 21 Jul 2025
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 120 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults (age ≥ 18 years)
New onset BSI due to Serratia marcescens, Providencia spp., Morganella morganii, Citrobacter freundii, and Enterobacter 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 study pathogens with concomitant growth in blood of skin commensals considered as contaminants.

Who cannot join

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

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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) or patient in palliative care

Trial locations and contacts

4 sites in 1 country.

Israel4 sites

Rambam Health Care Campus
Haifa
Hadassah Medical Center
Jerusalem
Rabin Medical Center, Beilinson Hospital
Petah Tikva
Sheba Tel HaShomer Medical Campus
Ramat Gan

Other trials in Israel

About this study

Official title: PipEracillin/Tazobactam vs mERoPENem for Treatment of AmpC-producing Bloodstream Infections: an Extension of the Original PETERPEN Trial

Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacterales bloodstream 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.

Read the detailed description

PeterPen-SPICE-M will expland the PeterPen trial. In PeterPen we recruit patients with bacteremia caused by 3rd generation cephalosporin-resistant E. coli or Klebsiella pneumoniae. In SPICE-M we will recruit also patients with bacteremia caused by 3rd generation cephalosporin-resistant Serratia marcescens, Providencia stuartii \& rettgeri, Indole positive Proteus spp. (Proteus vulgaris), Citrobacter freundii, Enterobacter cloacae, Klebsiella aerogenes and Morganella morganii. In both trials patients will be allocated within 72 hours of blood culture taking to piperacillin-tazobactam vs. meropenem to complete at least 7 days of covering antibiotic therapy.

Conditions: Beta Lactam Resistant Bacterial Infection, Enterobacteriaceae Infections, Bacteremia
Being tested: Piperacillin / Tazobactam Injection, Meropenem
Keywords: bacteremia, enterobacteriaceae, extended spectrum beta-lactamase, meropenem, piperacillin tazobactam
Medical subject headings: Enterobacteriaceae Infections, Bacteremia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Piperacillin / Tazobactam InjectionDrug
4.5 grams QID
MeropenemDrug
1 gram TID

Study groups in NCT05355350
Study group	Role	What they receive
piperacillin tazobactam	Experimental	Not described Receives: Drug: Piperacillin / Tazobactam Injection
meropenem	Active comparator	Not described Receives: Drug: Meropenem

What is being measured

The primary outcome is the main question the study is designed to answer.

All-cause mortality
Primary Outcome Measure
Measured: 30 days from randomization
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
Measured: 7 days from randomization]

Secondary outcomes (12)

All-cause mortality
Number of deceased patients
Measured: 14 and 90 days from randomization]
Number of participants with 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
Measured: 14 days and 30 days from randomization
Number of participants with microbiological failure
Repeat positive blood cultures with index pathogen on day 4 or later from randomization
Measured: 7 days and 14 days from randomization
Number of participants with recurrent positive blood cultures (relapse)
recurrent positive blood cultures with the index pathogen after prior sterilization of blood cultures or after end of treatment
Measured: 30 days and 90 days from randomization
Number of participants with Clostridium difficile associated diarrhea
Diarrhea with positive Clostridium difficile toxin test
Measured: 90 days from randomization
Secondary bacterial infections
Number of participants with a new clinically-significant infection, with or without microbiological documentation. Defined using NHSN criteria for healthcare-associated infections.
Measured: 90 days from randomization
Number of participants with hospital re-admissions
Hospital re-admission, excluding index hospitalization
Measured: 90 days from randomization
Number of participants with development of antimicrobial resistance
clinical isolates resistant to piperacillin/tazobactam and meropenem and any carbapenem-resistant bacteria
Measured: 90 days from randomization
Carriage of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae in-hospital detected by weekly rectal surveillance of carriage while in-hospital
New acquisition of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae, detected through rectal surveillance or clinical cultures
Measured: 90 days from randomization
Total in-hospital days
Total of in-hospital days per participant, including all admissions
Measured: 30 days and 90 days from randomization
Total antibiotic days
Total antibiotic days per participant within all admissions
Measured: 30 days and 90 days from randomization
Adverse events
diarrhea, liver function test abnormalities, antibiotic rash or other immediate-type allergy, acute kidney injury defined according to RIFLE criteria
Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 202221 Jul 2025

First posted2 May 2022
Study start1 Jul 2022
Primary completion21 Jul 2025
Study completion21 Jul 2025

Why it stopped: No eligible patients

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Beta Lactam Resistant Bacterial InfectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05355350
Sponsor's protocol ID: 0295-18-RMB
Acronym: SPICE-M
Status last verified: Jul 2025
First submitted: 4 Apr 2022
Last updated: 24 Jul 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Diagnostic Performance and Acceptability of Rectal Swab for Screening of ESBL Enterobacterales
Enterobacteriaceae, Swabs
RecruitingObservational study
Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa
Pseudomonas Infections, Pseudomonas Aeruginosa
Not yet recruitingObservational study
Prevalence of Carriage of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacteria in Preterm Premature Rupture of Membranes : A French Multicenter Cohort Study
Premature Rupture of Membranes, Enterobacteriaceae
RecruitingPhase 4
PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)
Beta Lactam Resistant Bacterial Infection, Enterobacteriaceae Infections

All Beta Lactam Resistant Bacterial Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: PipEracillin/Tazobactam vs mERoPENem for Treatment of AmpC-producing Bloodstream Infections: an Extension of the Original PETERPEN Trial
ClinicalTrials.gov ID: NCT05355350
Acronym / sponsor ID: SPICE-M / 0295-18-RMB
Conditions: Beta Lactam Resistant Bacterial Infection, Enterobacteriaceae Infections, Bacteremia
Keywords: bacteremia, enterobacteriaceae, extended spectrum beta-lactamase, meropenem, piperacillin tazobactam
Phase: Phase 4
Study type: Interventional
Recruitment status: WithdrawnReason stopped: No eligible patients
Enrolment: 0 participants (actual)
Lead sponsor: Rambam Health Care CampusUniversity, hospital or other
Collaborators: The Chaim Sheba Medical Center, Rabin Medical Center, Hadassah Medical Organization
Study start: 1 Jul 2022 (actual)
Primary completion: 21 Jul 2025 (actual)
Study completion: 21 Jul 2025 (actual)
First posted: 2 May 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
piperacillin tazobactam	Experimental	Drug: Piperacillin / Tazobactam Injection
meropenem	Active comparator	Drug: Meropenem

Who may qualify

Ages: 18 to 120 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Adults (age ≥ 18 years)
New onset BSI due to Serratia marcescens, Providencia spp., Morganella morganii, Citrobacter freundii, and Enterobacter 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 study pathogens with concomitant growth in blood of skin commensals considered as contaminants.

Key exclusion criteria (12 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Piperacillin / Tazobactam Injection4.5 grams QID	Drug	piperacillin tazobactam
Meropenem1 gram TID	Drug	meropenem

Primary outcome

All-cause mortality
Time frame: 30 days from randomization
Primary Outcome Measure
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

12 secondary outcomes

All-cause mortality
Time frame: 14 and 90 days from randomization]
Number of participants with treatment failure
Time frame: 14 days and 30 days from randomization
Number of participants with microbiological failure
Time frame: 7 days and 14 days from randomization
Number of participants with recurrent positive blood cultures (relapse)
Time frame: 30 days and 90 days from randomization
Number of participants with Clostridium difficile associated diarrhea
Time frame: 90 days from randomization
Secondary bacterial infections
Time frame: 90 days from randomization
Number of participants with hospital re-admissions
Time frame: 90 days from randomization
Number of participants with development of antimicrobial resistance
Time frame: 90 days from randomization
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
Total in-hospital days
Time frame: 30 days and 90 days from randomization
Total antibiotic days
Time frame: 30 days and 90 days from randomization
Adverse events
Time frame: 30 days

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2025.
Individual participant dataSharing planned: 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.

Related trials for Beta Lactam Resistant Bacterial Infection

Active, not recruiting
Diagnostic Performance and Acceptability of Rectal Swab for Screening of ESBL Enterobacterales
Enterobacteriaceae, Swabs
RecruitingObservational study
Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa
Pseudomonas Infections, Pseudomonas Aeruginosa
Not yet recruitingObservational study
Prevalence of Carriage of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacteria in Preterm Premature Rupture of Membranes : A French Multicenter Cohort Study
Premature Rupture of Membranes, Enterobacteriaceae
RecruitingPhase 4
PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)
Beta Lactam Resistant Bacterial Infection, Enterobacteriaceae Infections

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mical Paul, MD principal investigator

Rambam Health Care Campus

Dafna Yahav, MD principal investigator

Sheba Tel HaShomer Medical Campus

Alaa Atamna, MD principal investigator

Rabin Medical Center, Beilinson Campus

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 24 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-cause mortality (time frame: 30 days from randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05355350.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2025.