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

NCT ID: NCT05355350

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2025-07-21

Brief Summary

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

piperacillin tazobactam

Group Type: EXPERIMENTAL

Piperacillin / Tazobactam Injection

Intervention Type: DRUG

4.5 grams QID

meropenem

Group Type: ACTIVE_COMPARATOR

Meropenem

Intervention Type: DRUG

1 gram TID

Interventions

Piperacillin / Tazobactam Injection

4.5 grams QID

Intervention Type: DRUG

Meropenem

1 gram TID

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adults (age ≥ 18 years)

2. 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.

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 study pathogens 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) or patient in palliative care

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Chaim Sheba Medical Center

OTHER

Sponsor Role: collaborator

Rabin Medical Center

OTHER

Sponsor Role: collaborator

Hadassah Medical Organization

OTHER

Sponsor Role: collaborator

Rambam Health Care Campus

OTHER

Sponsor Role: lead

Responsible Party

MICHAL PAUL md

Prof. Mical Paul, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mical Paul, MD

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus

Dafna Yahav, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Tel HaShomer Medical Campus

Alaa Atamna, MD

Role: PRINCIPAL_INVESTIGATOR

Rabin Medical Center, Beilinson Campus

Roni Bitterman, MD

Role: STUDY_DIRECTOR

Rambam Health Care Campus

Noa Eliakim-Raz, MD

Role: STUDY_DIRECTOR

Rabin Medical Center, Beilinson Campus

Locations

Rambam Health Care Campus

Haifa, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Rabin Medical Center, Beilinson Hospital

Petah Tikva, , Israel

Sheba Tel HaShomer Medical Campus

Ramat Gan, , Israel

Countries

Israel

Other Identifiers

0295-18-RMB

Identifier Type: -

Identifier Source: org_study_id