Clinical Trial: Duration of Antibiotics for the Treatment of Gram-negative Bacilli Bacteremia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Duration of Antibiotics for the Treatment of Gram-negative Bacilli Bacteremia - a Randomized Controlled Trial

Brief Summary: 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.

Detailed Summary:
Sponsor: Rabin Medical Center

Current Primary Outcome:

  • composite of the following [ Time Frame: Until day 90 after randomization ]
    The primary outcome is a composite of the following outcome measures
  • All -cause mortality [ Time Frame: Until day 90 after randomization ]
    All- cause mortality
  • Treatment Failure [ Time Frame: Until day 90 after randomization ]

    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
  • Hospital re-admissions or extended hospitalization [ Time Frame: Until day 90 after randomization ]

    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 treatme

    Original Primary Outcome:

    • All -cause mortality [ Time Frame: Until day 90 after randomization ]
      All- cause mortality
    • Treatment Failure [ Time Frame: Until day 90 after randomization ]
      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
    • Infection caused by other than gram-negative bacteremia [ Time Frame: Until day 90 after randomization ]
      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


    Current Secondary Outcome:

    • Clostridium difficile associated diarrhea [ Time Frame: Until day 30 after randomization ]
      Clostridium difficile associated diarrhea
    • Development of Antibiotic resistance [ Time Frame: Until day 30 after randomization ]
      Development of resistance, defined as clinical isolates resistant to antibiotics previously used in the bacteremia episode. Surveillance sampling will not be conducted.
    • Carriage of carbapenem resistant Klebsiella pneumonia. [ Time Frame: Until day 30 after randomization ]
      Carriage of carbapenem resistant Klebsiella pneumonia (screened routinely)
    • Total in hospital days [ Time Frame: Until day 90 after randomization. ]
      Total in hospital days within 30 and 90 days
    • Total antibiotic days [ Time Frame: Until day 30 after randomization ]
      Total antibiotic days
    • Adverse events [ Time Frame: Until day 30 after randomization ]
      • 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
    • Infection caused by other than gram-negative bacteremia [ Time Frame: Until day 90 after randomization ]
      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
    • Number of hospital re-admissions [ Time Frame: Until day 90 after randomization ]
      Number of hospital re-admissions until day 90
    • Functional capacity and time to return to baseline activity [ Time Frame: Until day 30 after randomization ]
      Functional capacity and time to return to baseline activity


    Original Secondary Outcome:

    • Clostridium difficile associated diarrhea [ Time Frame: Until day 30 after randomization ]
      Clostridium difficile associated diarrhea
    • Hospital re-admissions [ Time Frame: Until day 90 after randomization ]
      Number of hospital re-admissions until day 90
    • Development of Antibiotic resistance [ Time Frame: Until day 30 after randomization ]
      Development of resistance, defined as clinical isolates resistant to antibiotics previously used in the bacteremia episode. Surveillance sampling will not be conducted.
    • Carriage of carbapenem resistant Klebsiella pneumonia. [ Time Frame: Until day 30 after randomization ]
      Carriage of carbapenem resistant Klebsiella pneumonia (screened routinely)
    • Total in hospital days [ Time Frame: Until day 30 after randomization. ]
      Total in hospital days
    • Total antibiotic days [ Time Frame: Until day 30 after randomization ]
      Total antibiotic days
    • Adverse events [ Time Frame: Until day 30 after randomization ]
      • 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


    Information By: Rabin Medical Center

    Dates:
    Date Received: November 14, 2012
    Date Started: January 2013
    Date Completion: July 2019
    Last Updated: August 8, 2016
    Last Verified: August 2016