Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT
Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT
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
Inclusion Criteria:

 -  Patient is in the ICU at time the blood culture result reported as positive AND

 -  Patient has a positive blood culture with pathogenic bacteria.

 Exclusion Criteria:

 -  Patient already enrolled in the trial

 -  Patient has severe immune system compromise, as defined by: absolute neutrophil count
 <0.5x109/L; or is receiving immunosuppressive treatment for solid organ or bone marrow
 or stem cell transplant

 -  Patient has syndrome with well-defined requirement for prolonged treatment:

 -  infective endocarditis

 -  osteomyelitis/septic arthritis

 -  undrainable/undrained abscess

 -  unremovable/unremoved prosthetic-associated infection

 -  Patient has a single positive blood culture with a common contaminant organism
 according to Clinical Laboratory & Standards Institute (CLSI) Guidelines: coagulase
 negative staphylococci; or Bacillus spp.; or Corynebacterium spp.; or
 Propionobacterium spp.; or Aerococcus spp.; or Micrococcus spp.

 -  Patient has a positive blood culture with Staphylococcus aureus.

 -  Patient has a positive blood culture with Candida spp. or other fungal species.