BALANCE on the Wards: A Pilot RCT
BALANCE on the Wards: A Pilot RCT
The burden of bloodstream infections is large and increasing over time. Antibiotic overuse
 continues to drive increased rates of antimicrobial-resistant pathogens across Canada.
 However, prospective audits have revealed that 30-50% of antibiotic utilization is
 unnecessary or inappropriate. If shorter duration therapy is as effective as longer duration
 therapy for these infections, antimicrobial consumption would be decreased. A pilot trial
 (approved by the Sunnybrook Research Ethics Board), is underway in critically ill patients at
 17 Canadian ICUs. Investigators have successfully demonstrated feasibility with respect to
 protocol adherence and recruitment rates in the ICU. Investigators now aim to conduct a
 similar pilot RCT among non-ICU patients admitted to hospital wards with bloodstream
 infections to determine feasibility and protocol adherence of the same trial protocol.
Bloodstream infections are a common and serious problem, and are associated with increased
 morbidity and mortality. At the same time, antibiotic overuse is also a common and serious
 problem, in that 30-50% of antibiotic use is unnecessary or inappropriate, and results in
 avoidable drug side effects such as kidney failure, Clostridium difficile infection,
 increased costs, and spiraling antibiotic resistance rates. The greatest contributor to
 antibiotic overuse is excessive durations of treatment.

 Extensive research has demonstrated that shorter duration antibiotic treatment (less or equal
 to 7 days) is as effective as longer duration treatment for a variety of infectious diseases,
 but this question has not been directly studied in the setting of bloodstream infection. Our
 team's systematic review of the medical literature, national survey of Canadian infectious
 diseases and critical care physicians, and multicentre retrospective study all support the
 need for a randomized controlled trial comparing shorter (7 days) versus longer (14 days)
 antibiotic therapy for bloodstream infections.

 Prior to performing the main trial, our pilot RCT in critically ill patients is
 near-completion.

 In order to increase the generalizability to non-critically ill patients, Investigators want
 to conduct a similar pilot RCT in non-critically ill patients (BALANCE on the Wards) to
 establish the feasibility of the research design, and to optimize the definitive trial.

 Investigators will conduct a randomized concealed allocation trial of shorter duration (7
 days) versus longer duration (14 days) antibiotic treatment for patients with bloodstream
 infections across all non-ICU hospital wards in Sunnybrook Hospital (BALANCE on the Wards).
 Our ongoing BALANCE pilot RCT in ICU is approved by the Sunnybrook REB (PIN: 187-2014). The
 BALANCE on Wards pilot trial will use the same protocol, informed consent form and the case
 report forms that are approved by the Sunnybrook REB with minimal changes to make it ward
 specific. If the investigators are able to achieve the primary outcome of this trial in
 Sunnybrook hospital, the main BALANCE trial will potentially involve enrolment of non-ICU
 patients at all (or a subset of) participating sites.

 If eligibility criteria and study procedures are substantially unchanged, results of the both
 the pilot BALANCE RCTs will be rolled into the dataset for the main BALANCE RCT.
Inclusion Criteria:

 1. Patient is in the hospital ward and not in the intensive care units at time the blood
 culture result reported as positive AND

 2. Patient has a positive blood culture with pathogenic bacteria

 Exclusion Criteria:

 1. Patient already enrolled in either of the BALANCE trials

 2. Patient is admitted in the ICU at the time of enrollment

 3. 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

 4. Patient has a prosthetic heart valve or synthetic endovascular graft

 5. Patient has documented or suspicion of syndrome with well-defined requirement for
 prolonged treatment:

 i) infective endocarditis; ii) osteomyelitis/septic arthritis; iii)
 undrainable/undrained abscess; iv) unremovable/unremoved prosthetic-associated
 infection

 6. 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.

 7. Patient has a positive blood culture with Staphylococcus aureus.

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