Last updated on November 2019

Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness

Brief description of study

The World Health Organization, U.S. Centers for Disease Control and Prevention, Association of Medical Microbiology and Infectious Diseases (AMMI) Canada, and Health Canada have all declared antimicrobial resistance a global threat to health, based on rapidly increasing resistance rates and declining new drug development. Up to 30-50% of antibiotic use is inappropriate, and excessive durations of treatment are the greatest contributor to inappropriate use. Shorter duration treatment (7 days) has been shown in meta-analyses to be as effective as longer antibiotic treatment for a range of mild to moderate infections. A landmark trial in critically ill patients with ventilator-associated pneumonia showed that mortality and relapse rates were non-inferior in patients who received 8 vs 15 days of treatment. Similar randomized trial evidence is lacking for the treatment of patients with bloodstream infection, which affects 15% of critically ill patients, and an estimated 50,000 Canadians per year.

Detailed Study Description

Bloodstream infections are a common and serious problem, affecting 15% of critically ill patients, increasing length of hospital stay by 2-3 weeks, adding $25,000-40,000 in excess hospital costs, and tripling the risk of death. 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, multicentre retrospective study and BALANCE pilot RCT, 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, we completed a pilot trial to establish the feasibility of the research design, and to optimize the definitive trial. By defining the duration of treatment for bloodstream infections, our research program will help maximize the clinical cure of individual patients, while minimizing their risk of drug side effects, C. difficile, and antibiotic resistance. Since this intervention would require no new technology, and would reduce (rather than increase) health care costs, it would offer immediate benefits to patients and the healthcare system.

The BALANCE RCT will randomize critically ill patients with bloodstream infection to 7 versus 14 days of adequate antibiotic treatment; the antibiotic drugs, doses, routes and interval will be left to the discretion of the treating team. Although placebo controls are not feasible, prolonged allocation concealment to day 7 will be used to mitigate selection bias. The primary analysis will assess whether 7 days is associated with non-inferior 90 day survival as compared to 14 days of treatment. Patients from the vanguard BALANCE pilot RCT will be included in the BALANCE main RCT, and participating Canadian sites will continue to enrol patients (ultimately 20-25 Canadian sites will be included). BALANCE international collaborators in New Zealand, Australia, Saudi Arabia, the United States, France and Germany are working towards inclusion of sites, to facilitate target sample size recruitment within 5 years.

Clinical Study Identifier: NCT03005145

Find a site near you

Start Over

Cabrini Health

Melbourne, Australia
  Connect »

St. Paul's Hospital

Vancouver, BC Canada
  Connect »

Niagara Health System

St. Catharines, ON Canada
  Connect »

Middlemore Hospital

Auckland, New Zealand
  Connect »

Christchurch Hospital

Christchurch, New Zealand
  Connect »

Wellington Hospital

Wellington, New Zealand
  Connect »

NYU School of Medicine

New York, NY United States
  Connect »

Cleveland Clinic

Cleveland, OH United States
  Connect »

Waikato Hospital

Hamilton, New Zealand
  Connect »

Taranaki Hospital

New Plymouth, New Zealand
  Connect »

Rotorua Hospital

Rotorua, New Zealand
  Connect »