Grant: Operating Grant: Clinical Trials Projects

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 is comparing 7 versus 14 days of antibiotic treatment for bloodstream infection and has recruited nearly 3000 patients across 73 hospitals. BALANCE is the largest trial ever conducted among patients with bloodstream infection, and when it concludes next year will answer a fundamental treatment duration question. However, many crucial questions will remain. BALANCE+ will 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. This trial provides a platform upon which to answer three questions looking at best ways to 'de-escalate' and 'step-down' antibiotic treatment (going from a broad to more specific antibiotic). We will answer the question about what to do when the infection is caused by bacteria on an intravenous catheter - should we remove and replace the catheter or just treat with antibiotics. We will also answer some key antibiotic selection controversies for some difficult to treat 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. 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.