The investigators plan an open label randomized controlled trial to compare short-course antibiotic therapy (\<=7 days) versus longer treatment (\>7 days). The investigators will include hospitalized patients with gram-negative bacteremia. The investigators primary objective is to investigate the safety and efficacy of short-course antibiotics.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
604
On day 7 of appropriate intravenous or oral antibiotic treatment for the bacteremic episode (day 1 is the first day of appropriate antibiotic therapy), patients will be randomized to: 1. Intervention group - antibiotic treatment stopped on day 7 2. Control group - antibiotic treatment continued for 14 days according to accepted hospital local guidelines.
Rambam Health Care Center
Haifa, Israel
Rabin medical center, Beilinson Hospital
Petah Tikvah, Israel
Policlinico di Modena, Italy
Modena, Emilia-Romagna, Italy
composite of the following
The primary outcome is a composite of the following outcome measures
Time frame: Until day 90 after randomization
All -cause mortality
All- cause mortality
Time frame: Until day 90 after randomization
Treatment Failure
Failure including any of the following: 1. Relapse: a recurrent bacteraemia due to the same microorganism occurring from day of randomization and until day 9013 2. Local suppurative complication that was not present at infection onset (e.g. renal abscess in pyelonephritis, empyema in pneumonia) 3. Distant complications of initial infection, defined by growth of the same bacteria as in the initial bacteremia
Time frame: Until day 90 after randomization
Hospital re-admissions or extended hospitalization
We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome. We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome.
Time frame: Until day 90 after randomization
Clostridium difficile associated diarrhea
Clostridium difficile associated diarrhea
Time frame: Until day 30 after randomization
Development of Antibiotic resistance
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Development of resistance, defined as clinical isolates resistant to antibiotics previously used in the bacteremia episode. Surveillance sampling will not be conducted.
Time frame: Until day 30 after randomization
Carriage of carbapenem resistant Klebsiella pneumonia.
Carriage of carbapenem resistant Klebsiella pneumonia (screened routinely)
Time frame: Until day 30 after randomization
Total in hospital days
Total in hospital days within 30 and 90 days
Time frame: Until day 90 after randomization.
Total antibiotic days
Total antibiotic days
Time frame: Until day 30 after randomization
Adverse events
* Any diarrhea * Liver function test abnormalities, defined as elevated bilirubin x 1.5 of upper limit of normal or transaminases x 2.5 of upper limit of normal * Antibiotic rash * Acute kidney injury - defined according to RIFLE criteria as increased creatinine level x 1.5 from baseline or glomerular filtration rate (GFR) decrease \>25% or urine output of \<0.5 ml/kg/h for 6 hours22
Time frame: Until day 30 after randomization
Infection caused by other than gram-negative bacteremia
Development of either clinically or microbiologically documented infection other than gram-negative bacteremia. We will use the 2008 CDC/NHSN surveillance definitions of health-care associated infections for bacterial infections
Time frame: Until day 90 after randomization
Number of hospital re-admissions
Number of hospital re-admissions until day 90
Time frame: Until day 90 after randomization
Functional capacity and time to return to baseline activity
Functional capacity and time to return to baseline activity
Time frame: Until day 30 after randomization