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.
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.
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.
Parallel
Piperacillin/tazobactam
Drug4.5 grams QID
Meropenem
Drug1 gram TID
All-cause mortality
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
All-cause mortality
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
Microbiological failure
Repeat positive blood cultures with index pathogen on day 4 or later from randomization
Recurrent positive blood cultures (relapse)
recurrent positive blood cultures with the index pathogen after prior sterilization of blood cultures or after end of treatment
Click on the lead sponsor to view all of their trials.
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
