Determining the Optimal Duration of Antibiotic Treatment in Older Adults Living with Frailty with Bloodstream Infection

The Canadian Federal Government, United States Centres for Disease Control and the World Health Organization, have all identified antimicrobial resistance as an urgent, global public health threat given rising rates of resistance among important bacterial pathogens and declining new antibiotic drug discovery. Antimicrobial resistance is being driven by high rates of inappropriate antimicrobial use, including unnecessarily prolonged antibiotic treatment courses. The older patient living with frailty population is particularly susceptible to both community- and hospital-acquired infections, and to the untoward effects of factors prolonging lengths of stay in hospital.

About the Project

Bloodstream infections affect more than 40,000 Canadians per year, and are associated with high morbidity, mortality and healthcare costs.  At the same time, antibiotic overuse is 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, prolonged hospital stays and spiralling antibiotic resistance rates.  The risks and benefits of antibiotic treatment are particularly difficult to balance in older patients living with frailty, given that they are at heightened risk of infection-related complications as well as antibiotic treatment-related complications.

Perhaps the best way to balance these benefits and risks is by optimizing duration of treatment.  Shorter duration treatment (= 7 days) is as effective as longer treatment for infectious diseases such as urinary tract infection and pneumonia, but this question has not been directly studied for bloodstream infection. Our team’s systematic review of the medical literature, national clinician survey, multicentre retrospective study, and pilot randomized controlled trial (RCT) all supported the need for a trial comparing shorter versus longer antibiotic treatment for bloodstream infections. To this end we have recently launched the Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) RCT, aiming to enroll 3600 critically ill patients with bloodstream infection; in this current application we seek to extend enrolments beyond the critical care unit to include all older patients living with frailty admitted to hospital with bloodstream infection.

Main objective of Ongoing BALANCE Trial:  To test whether shorter duration antibiotic treatment (7 days) for critically ill patients with bloodstream infection is associated with non-inferior survival rates (at 90 days) to those achieved with longer duration treatment (14 days). To expand BALANCE trial enrolments outside of the intensive care unit, to include all frail elderly patients admitted to the hospital with bloodstream infection.

The project will seek to expand hospital wide within 12 months.  Critical milestones will include: (1) research ethics board amendments at all participating hospitals, (2) run-in piloting of hospital-wide expansion at each site, (3) full active hospital-wide enrolment at each site.

Project Team

Principal Investigators:

Nick Daneman, MD, FRCPC, M.Sc., Scientist and Assistant Professor, Faculty of Medicine, Sunnybrook Health Sciences Centre

Robert Fowler, MD, MDCM, M.Sc., Scientist and Professor, Faculty of Medicine and and Critical Care Medicine, Sunnybrook Health Sciences Centre


Kenneth Rockwood, MD FRCPC FRCP, Professor, Divisionon of Geriatric Medicine, Dalhousie University

Barbara Liu, MD, Scientist and Associate Professor, Division of Geriatric Medicine, Sunnybrook Health Sciences Centre

Deborah Cook, MD, FRCPC, MSc(Epid), CRC, CAHS, FRS, Professor, Department of Medicine and Critical Care,  McMaster University

Bryan Coburn, MD, PhD, FRCPC, Clinician-Scientist in the Division of Infectious Diseases, University Health Network, University of Toronto

Project Contact: Nick Daneman —


Keywords: Bloodstream infection; bacteremia; frailty; antibiotic treatment; duration of therapy; mortality; antibiotic resistance; Clostridium difficile; adverse events; randomized controlled trial