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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,084
4.5 grams QID
1 gram TID
University of Calgary, Cumming School of Medicine, O'Brien Institute for Public Health
Calgary, Alberta, Canada
RECRUITINGSurrey Memorial Hospital - Fraser Health Authority
Surrey, British Columbia, Canada
RECRUITINGEastern Health
St. John's, Newfoundland and Labrador, Canada
RECRUITINGKingston General Hospital
Kingston, Ontario, Canada
RECRUITINGJewish Genral Hospital
Montreal, Quebec, Canada
RECRUITINGMcGill University Health Centre
Montreal, Quebec, Canada
RECRUITINGRambam Health Care Campus
Haifa, Israel, Israel
RECRUITINGSoroka Medical Center
Beersheba, Israel
RECRUITINGHadassah Medical Center
Jerusalem, Israel
RECRUITINGMeir Medical Center
Kfar Saba, Israel
RECRUITING...and 4 more locations
All-cause mortality
Time frame: 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
Time frame: 7 days from randomization
All-cause mortality
Time frame: 14 and 90 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
Time frame: 14 days and 30 days from randomization
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
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
Clostridium difficile associated diarrhea
Time frame: 90 days from randomization
Clinically or microbiologically documented infection other than Gram-negative bacteremia
Time frame: 90 days from randomization
Number of hospital re-admissions
Time frame: 90 days from randomization
Development of resistance
clinical isolates resistant to piperacillin/tazobactam and meropenem and any carbapenem-resistant bacteria
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
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
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