Grant: Project Grant

Bloodstream infections are a leading cause of death in Canada and worldwide, yet remain understudied, such that we do not know the best treatment strategies to be sure to cure the infection while minimizing harms of excess antibiotics causing antimicrobial resistance. Our Canadian Institutes of Health Research funded Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) Randomized Controlled Trial was the largest ever trial among patients with bloodstream infection, enrolling over 3600 patients across 74 sites in 7 countries. BALANCE confirmed that 7 days of antibiotics was as effective as 14 days, and set the paradigm for treatment duration. However, many crucial questions remain. BALANCE+ provides a platform to efficiently answer multiple next questions that are important for patients with the most common kind of bloodstream infections. All hospitalized adult patients with the most common kind of bloodstream infections - caused by "Gram negative" bacteria - will be eligible to participate. At launch this trial is addressing whether to repeat a blood culture to document clearance of infection, whether or not to 'de-escalate' (going from a broad to more specific antibiotic), the best oral antibiotics to use when switching from intravenous treatment, whether to replace or retain intravenous catheters, and specific antibiotic selection for a difficult to treat group ('AmpC') of pathogens. As each question is answered, optimal therapies will be adopted into usual care, and new questions will be introduced into the platform of the trial. In this proposal we ask for continuation funding to complete ongoing questions, and to add a new antibiotic duration question informed by BALANCE. The evidence generated by BALANCE+ will improve cure for this vulnerable patient population while decreasing potential harms from using too many antibiotics for too long.