<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02261506</url>
  </required_header>
  <id_info>
    <org_study_id>187-2014</org_study_id>
    <nct_id>NCT02261506</nct_id>
  </id_info>
  <brief_title>Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT</brief_title>
  <acronym>BALANCE</acronym>
  <official_title>Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Queen's University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bacteremia is a leading cause of mortality and morbidity in critically ill adults. Although&#xD;
      bacteria in the bloodstream (bacteremia) may arise from variable infectious foci (most&#xD;
      commonly central vascular catheter related, lung, urinary tract, intra-abdominal, or skin and&#xD;
      soft tissue sources), because of the high attendant morbidity and mortality of bacteremia,&#xD;
      these patients collectively represent a critically important group to study.&#xD;
&#xD;
      The consequences of the excessive antimicrobial use for individual patients, range from rash,&#xD;
      gastrointestinal upset and diarrhea, to anaphylaxis, neutropenia, renal failure, toxic&#xD;
      epidermal necrolysis, death, and a marked increase in ICU and hospital drug costs. One&#xD;
      particularly concerning complication, Clostridium difficile infection, has increased in&#xD;
      incidence and severity over the past decade. Much of this burden could be prevented through&#xD;
      reduction in unnecessary antibiotic use.&#xD;
&#xD;
      Another major consequence of excessive antibiotic use is antimicrobial resistance. Antibiotic&#xD;
      resistance is not only a concern for the patient who receives antibiotics, but also for&#xD;
      neighbouring patients in the ICU, as well as future patients in the ICU and the hospital at&#xD;
      large - through patient-to-patient transmission, and environmental contamination.&#xD;
&#xD;
      No previous randomized controlled trials have directly compared shorter versus longer&#xD;
      durations of antimicrobial treatment in these patients. The investigators will conduct a&#xD;
      multi-center randomized concealed allocation trial of shorter duration (7 days) versus longer&#xD;
      duration (14 days) antibiotic treatment for critically ill patients with bacteremia admitted&#xD;
      to ICU. Eligible, patients will be randomized to either 7 days or 14 days of adequate&#xD;
      antimicrobial treatment. The selection of type, dose and route of antibiotics will be at the&#xD;
      discretion of the treating physicians, but the duration of treatment (7 versus 14 days) will&#xD;
      be determined by randomization group. The randomization assignment will not be communicated&#xD;
      to the study research coordinator, study critical care or infectious diseases investigators&#xD;
      or clinicians until day 8. The primary outcome for the main trial will be 90-day mortality.&#xD;
&#xD;
      The study will be initiated at Sunnybrook Health Sciences Centre in Toronto, Ontario, and&#xD;
      then rolled out to a second site at Kingston General Hospital in Kingston, Ontario. These&#xD;
      sites will be sufficient to meet the sample size goals for the pilot RCT, but if additional&#xD;
      funds are obtained the investigators will also roll out to the other Canadian ICUs listed&#xD;
      below. The goal of adding these additional sites will be to increase the generalizability of&#xD;
      the findings with respect to trial feasibility&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2014</start_date>
  <completion_date type="Actual">October 5, 2017</completion_date>
  <primary_completion_date type="Actual">August 30, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adherence to treatment duration protocol (proportion of treatment courses)</measure>
    <time_frame>15 days</time_frame>
    <description>We will consider the main trial to be feasible and worthy of embarking on a larger mortality-powered RCT if 90% of antibiotic treatment courses are within 7± 2 days in the shorter duration treatment arm or 14 ± 2 days in the longer duration treatment arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of recruitment (patients per site, per month)</measure>
    <time_frame>For up to 1 year</time_frame>
    <description>We will consider the main trial to be feasible if we achieve recruitment rates of at least 1 patient per 4 weeks, on average, per participating site.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ICU mortality</measure>
    <time_frame>Recorded as alive or dead at ICU discharge following index positive blood culture for an expected average of 2 weeks assesses upto one year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital mortality</measure>
    <time_frame>recorded as alive or dead at hospital discharge following index positive blood culture for an expected average of 4 weeks assesses upto one year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>90 day mortality</measure>
    <time_frame>Recorded as alive or dead at 90 days following index positive blood culture</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse rates of bacteremia</measure>
    <time_frame>Upto 30 days after adequate antibiotic treatment</time_frame>
    <description>Defined as the recurrence of bacteremia due to original infecting organism (same Genus and species) after documentation of negative blood cultures or clinical improvement and within 30 days after completing course of adequate antimicrobial therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic allergy</measure>
    <time_frame>Up to 30 days from start of antibiotic treatment.</time_frame>
    <description>Effect of medication on body that produces the allergic reaction to a medication like:&#xD;
Hives&#xD;
Itching of the skin or eyes&#xD;
Skin rash&#xD;
Swelling of the lips, tongue, or face&#xD;
Wheezing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anaphylaxis</measure>
    <time_frame>Up to 30 days from start of antibiotic treatment</time_frame>
    <description>To be considered anaphylaxis, the patient must have had &gt;=1 of the following 3 criteria that a medical team member attributed to an Antimicrobial&#xD;
Acute onset of skin or mucosal tissue changes (hives, itching/flush, lip/tongue/uvula swelling) over minutes/hours, accompanied by&#xD;
respiratory compromise (dyspnea, wheeze, stridor, hypoxemia), AND/OR&#xD;
reduced blood pressure or symptoms/signs of end organ dysfunction from shock&#xD;
Rapid onset of two or more of the following&#xD;
involvement of the skin-mucosa (hives, itch//flush, swollen lips/tongue/uvula)&#xD;
respiratory compromise&#xD;
reduced BP or associated symptoms/signs&#xD;
persistent gastrointestinal symptoms/signs (crampy abdominal pain, vomiting)&#xD;
Reduced blood pressure after exposure to a known allergen for that patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antimicrobial-related acute kidney injury</measure>
    <time_frame>Up to 30 days from start of antibiotic treatment</time_frame>
    <description>To be considered Antimicrobial-associated renal injury, a medical team member must have attributed the renal injury to the Antimicrobial, and the severity of the renal injury must meet one of these (RIFLE criteria):&#xD;
Risk: GFR decrease &gt;25%, serum creatinine increased 1.5 times or urine production of &lt;0.5 ml/kg/hr for 6 hours&#xD;
Injury: GFR decrease &gt;50%, doubling of creatinine or urine production &lt;0.5 ml/kg/hr for 12 hours&#xD;
Failure: GFR decrease &gt;75%, tripling of creatinine or creatinine &gt;355 μmol/l (with a rise of &gt;44) (&gt;4 mg/dl) OR urine output below 0.3 ml/kg/hr for 24 hours&#xD;
Loss: persistent AKI or complete loss of kidney function for more than 4 weeks&#xD;
End-stage renal disease: need for renal replacement therapy (RRT) for more than 3 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antimicrobial-related hepatitis</measure>
    <time_frame>Up to 30 days from start of antibiotic treatment</time_frame>
    <description>To be considered Antimicrobial-associated hepatitis, a medical team member must have attributed the hepatitis to the Antimicrobial, and the severity of the hepatitis must meet this FDA criteria for hepatic adverse events:&#xD;
o ALT&gt; 3x the upper limit of normal</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of Clostridium difficile infection in hospital</measure>
    <time_frame>Upto 30 days after index blood culture collection date</time_frame>
    <description>Defined as a positive PCR or ELISA test for Clostridium difficile toxin in the context of diarrhea within hospital of bacteremia diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of secondary nosocomial infection with antimicrobial resistant organisms in hospital</measure>
    <time_frame>Upto 30 days after index blood culture collection date</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU lengths of stay</measure>
    <time_frame>For the duration of ICU stay, expected for an average of 30 days assessed up to 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital lengths of stay</measure>
    <time_frame>For the duration of Hospital stay, expected for an average of 30 days assessed up to 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical ventilation duration</measure>
    <time_frame>For the duration of ICU and Hospital stay, expected for an average of 30 days</time_frame>
    <description>Defined as the number of consecutive days receiving invasive (via an endotracheal tube or tracheostomy), or non-invasive (via a facemask, nasal mask, or helmet) ventilation. Durations will be calculated for all patients then separately for patients who died within hospital and those who did not die.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vasopressor duration in ICU</measure>
    <time_frame>For the duration of ICU and Hospital stay, expected for an average of 30 days</time_frame>
    <description>Defined as the number of consecutive days receiving intravenous vasoactive medications (e.g. epinephrine, norepinephrine, vasopressin, dopamine, phenylephrine, dobutamine, milrinone). Durations will be calculated for all patients then separately for patients who died within hospital and those who did not die.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">115</enrollment>
  <condition>Bacteremia</condition>
  <arm_group>
    <arm_group_label>7 days</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only</description>
  </arm_group>
  <arm_group>
    <arm_group_label>14 days</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>7 days of adequate antibiotic treatment durations</intervention_name>
    <description>We will not be randomizing patients to any specific antibiotic regimen. Patients will be randomized to fixed durations of adequate treatment: 7 versus 14 days. The selection of antibiotic(s) will be at the discretion of the treating team, although the research team will check to ensure that the selected antibiotics have an 'adequate' spectrum of coverage for the bacterial pathogen(s) isolated in the blood culture.</description>
    <arm_group_label>7 days</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>14 days of adequate antibiotic treatment durations</intervention_name>
    <arm_group_label>14 days</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient is in the ICU at time the blood culture result reported as positive AND&#xD;
&#xD;
          -  Patient has a positive blood culture with pathogenic bacteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient already enrolled in the trial&#xD;
&#xD;
          -  Patient has severe immune system compromise, as defined by: absolute neutrophil count&#xD;
             &lt;0.5x109/L; or is receiving immunosuppressive treatment for solid organ or bone marrow&#xD;
             or stem cell transplant&#xD;
&#xD;
          -  Patient has syndrome with well-defined requirement for prolonged treatment:&#xD;
&#xD;
               -  infective endocarditis&#xD;
&#xD;
               -  osteomyelitis/septic arthritis&#xD;
&#xD;
               -  undrainable/undrained abscess&#xD;
&#xD;
               -  unremovable/unremoved prosthetic-associated infection&#xD;
&#xD;
          -  Patient has a single positive blood culture with a common contaminant organism&#xD;
             according to Clinical Laboratory &amp; Standards Institute (CLSI) Guidelines: coagulase&#xD;
             negative staphylococci; or Bacillus spp.; or Corynebacterium spp.; or&#xD;
             Propionobacterium spp.; or Aerococcus spp.; or Micrococcus spp.&#xD;
&#xD;
          -  Patient has a positive blood culture with Staphylococcus aureus.&#xD;
&#xD;
          -  Patient has a positive blood culture with Candida spp. or other fungal species.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nick Daneman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Foothills Hospital</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Columbian Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Paul's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Boniface Hospital</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth II Hospital</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kingston General Hospital</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Western Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUM</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Université de Sherbrooke</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier affilié universitaire de Québec</name>
      <address>
        <city>Quebec</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CSSS de Trois-Rivières</name>
      <address>
        <city>Quebec</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>December 14, 2017</last_update_submitted>
  <last_update_submitted_qc>December 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sunnybrook Health Sciences Centre</investigator_affiliation>
    <investigator_full_name>Dr. Nick Daneman</investigator_full_name>
    <investigator_title>Clinician Scientist</investigator_title>
  </responsible_party>
  <keyword>Intensive care</keyword>
  <keyword>bacteremia</keyword>
  <keyword>bloodstream infection</keyword>
  <keyword>antimicrobial</keyword>
  <keyword>mortality</keyword>
  <keyword>antimicrobial stewardship</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bacteremia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Antibiotics, Antitubercular</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02261506
org study id: 187-2014
nct id: NCT02261506
lead sponsor: 
collaborator: 
has dmc: No
Bacteremia is a leading cause of mortality and morbidity in critically ill adults. Although
      bacteria in the bloodstream (bacteremia) may arise from variable infectious foci (most
      commonly central vascular catheter related, lung, urinary tract, intra-abdominal, or skin and
      soft tissue sources), because of the high attendant morbidity and mortality of bacteremia,
      these patients collectively represent a critically important group to study.

      The consequences of the excessive antimicrobial use for individual patients, range from rash,
      gastrointestinal upset and diarrhea, to anaphylaxis, neutropenia, renal failure, toxic
      epidermal necrolysis, death, and a marked increase in ICU and hospital drug costs. One
      particularly concerning complication, Clostridium difficile infection, has increased in
      incidence and severity over the past decade. Much of this burden could be prevented through
      reduction in unnecessary antibiotic use.

      Another major consequence of excessive antibiotic use is antimicrobial resistance. Antibiotic
      resistance is not only a concern for the patient who receives antibiotics, but also for
      neighbouring patients in the ICU, as well as future patients in the ICU and the hospital at
      large - through patient-to-patient transmission, and environmental contamination.

      No previous randomized controlled trials have directly compared shorter versus longer
      durations of antimicrobial treatment in these patients. The investigators will conduct a
      multi-center randomized concealed allocation trial of shorter duration (7 days) versus longer
      duration (14 days) antibiotic treatment for critically ill patients with bacteremia admitted
      to ICU. Eligible, patients will be randomized to either 7 days or 14 days of adequate
      antimicrobial treatment. The selection of type, dose and route of antibiotics will be at the
      discretion of the treating physicians, but the duration of treatment (7 versus 14 days) will
      be determined by randomization group. The randomization assignment will not be communicated
      to the study research coordinator, study critical care or infectious diseases investigators
      or clinicians until day 8. The primary outcome for the main trial will be 90-day mortality.

      The study will be initiated at Sunnybrook Health Sciences Centre in Toronto, Ontario, and
      then rolled out to a second site at Kingston General Hospital in Kingston, Ontario. These
      sites will be sufficient to meet the sample size goals for the pilot RCT, but if additional
      funds are obtained the investigators will also roll out to the other Canadian ICUs listed
      below. The goal of adding these additional sites will be to increase the generalizability of
      the findings with respect to trial feasibility
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adherence to treatment duration protocol (proportion of treatment courses)
time frame: 15 days
description: We will consider the main trial to be feasible and worthy of embarking on a larger mortality-powered RCT if 90% of antibiotic treatment courses are within 7± 2 days in the shorter duration treatment arm or 14 ± 2 days in the longer duration treatment arm.
measure: Rate of recruitment (patients per site, per month)
time frame: For up to 1 year
description: We will consider the main trial to be feasible if we achieve recruitment rates of at least 1 patient per 4 weeks, on average, per participating site.
measure: ICU mortality
time frame: Recorded as alive or dead at ICU discharge following index positive blood culture for an expected average of 2 weeks assesses upto one year.
measure: Hospital mortality
time frame: recorded as alive or dead at hospital discharge following index positive blood culture for an expected average of 4 weeks assesses upto one year.
measure: 90 day mortality
time frame: Recorded as alive or dead at 90 days following index positive blood culture
measure: Relapse rates of bacteremia
time frame: Upto 30 days after adequate antibiotic treatment
description: Defined as the recurrence of bacteremia due to original infecting organism (same Genus and species) after documentation of negative blood cultures or clinical improvement and within 30 days after completing course of adequate antimicrobial therapy.
measure: Antibiotic allergy
time frame: Up to 30 days from start of antibiotic treatment.
description: Effect of medication on body that produces the allergic reaction to a medication like:
Hives
Itching of the skin or eyes
Skin rash
Swelling of the lips, tongue, or face
Wheezing
measure: Anaphylaxis
time frame: Up to 30 days from start of antibiotic treatment
description: To be considered anaphylaxis, the patient must have had >=1 of the following 3 criteria that a medical team member attributed to an Antimicrobial
Acute onset of skin or mucosal tissue changes (hives, itching/flush, lip/tongue/uvula swelling) over minutes/hours, accompanied by
respiratory compromise (dyspnea, wheeze, stridor, hypoxemia), AND/OR
reduced blood pressure or symptoms/signs of end organ dysfunction from shock
Rapid onset of two or more of the following
involvement of the skin-mucosa (hives, itch//flush, swollen lips/tongue/uvula)
respiratory compromise
reduced BP or associated symptoms/signs
persistent gastrointestinal symptoms/signs (crampy abdominal pain, vomiting)
Reduced blood pressure after exposure to a known allergen for that patient
measure: Antimicrobial-related acute kidney injury
time frame: Up to 30 days from start of antibiotic treatment
description: To be considered Antimicrobial-associated renal injury, a medical team member must have attributed the renal injury to the Antimicrobial, and the severity of the renal injury must meet one of these (RIFLE criteria):
Risk: GFR decrease >25%, serum creatinine increased 1.5 times or urine production of <0.5 ml/kg/hr for 6 hours
Injury: GFR decrease >50%, doubling of creatinine or urine production <0.5 ml/kg/hr for 12 hours
Failure: GFR decrease >75%, tripling of creatinine or creatinine >355 μmol/l (with a rise of >44) (>4 mg/dl) OR urine output below 0.3 ml/kg/hr for 24 hours
Loss: persistent AKI or complete loss of kidney function for more than 4 weeks
End-stage renal disease: need for renal replacement therapy (RRT) for more than 3 months
measure: Antimicrobial-related hepatitis
time frame: Up to 30 days from start of antibiotic treatment
description: To be considered Antimicrobial-associated hepatitis, a medical team member must have attributed the hepatitis to the Antimicrobial, and the severity of the hepatitis must meet this FDA criteria for hepatic adverse events:
o ALT> 3x the upper limit of normal
measure: Rates of Clostridium difficile infection in hospital
time frame: Upto 30 days after index blood culture collection date
description: Defined as a positive PCR or ELISA test for Clostridium difficile toxin in the context of diarrhea within hospital of bacteremia diagnosis.
measure: Rates of secondary nosocomial infection with antimicrobial resistant organisms in hospital
time frame: Upto 30 days after index blood culture collection date
measure: ICU lengths of stay
time frame: For the duration of ICU stay, expected for an average of 30 days assessed up to 1 year.
measure: Hospital lengths of stay
time frame: For the duration of Hospital stay, expected for an average of 30 days assessed up to 1 year.
measure: Mechanical ventilation duration
time frame: For the duration of ICU and Hospital stay, expected for an average of 30 days
description: Defined as the number of consecutive days receiving invasive (via an endotracheal tube or tracheostomy), or non-invasive (via a facemask, nasal mask, or helmet) ventilation. Durations will be calculated for all patients then separately for patients who died within hospital and those who did not die.
measure: Vasopressor duration in ICU
time frame: For the duration of ICU and Hospital stay, expected for an average of 30 days
description: Defined as the number of consecutive days receiving intravenous vasoactive medications (e.g. epinephrine, norepinephrine, vasopressin, dopamine, phenylephrine, dobutamine, milrinone). Durations will be calculated for all patients then separately for patients who died within hospital and those who did not die.
arm group label: 7 days
arm group type: Active Comparator
description: Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only
arm group label: 14 days
arm group type: Active Comparator
description: Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only
intervention type: Other
intervention name: 7 days of adequate antibiotic treatment durations
description: We will not be randomizing patients to any specific antibiotic regimen. Patients will be randomized to fixed durations of adequate treatment: 7 versus 14 days. The selection of antibiotic(s) will be at the discretion of the treating team, although the research team will check to ensure that the selected antibiotics have an 'adequate' spectrum of coverage for the bacterial pathogen(s) isolated in the blood culture.
arm group label: 7 days
intervention type: Other
intervention name: 14 days of adequate antibiotic treatment durations
arm group label: 14 days
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nick Daneman, MD
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre
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country: Canada
responsible party type: Principal Investigator
investigator affiliation: Sunnybrook Health Sciences Centre
investigator full name: Dr. Nick Daneman
investigator title: Clinician Scientist
mesh term: Bacteremia
mesh term: Anti-Bacterial Agents
mesh term: Antibiotics, Antitubercular