The BALANCE trial suggests that shorter treatment durations may reduce healthcare costs, antibiotic exposure, and antimicrobial resistance risk, providing an alternative for critically ill patients.
Nick Daneman, MD, FRCPC, MSc.
Image credits: University of Toronto
A large randomized controlled trial has found that 7 days of antibiotic treatment for bloodstream infections is noninferior to the standard 14-day regimen. The BALANCE trial, published in The New England Journal of Medicine, involved 3,608 hospitalized patients across 74 hospitals in seven countries. By 90 days, 14.5% of patients in the 7-day group had died, compared to 16.1% in the 14-day group , a difference of 1.6 percentage points (95.7% CI, −4 to 0.8). These findings suggest that shorter antibiotic courses may be a viable option for many patients, especially those who are critically ill.1
The trial included a diverse range of hospitalized patients with bloodstream infections, 75.4% of which were community-acquired, and 42.2% originated from the urinary tract. Over half (55%) of participants were critically ill and in the ICU. The trial also showed consistent results across secondary outcomes, including rates of C difficile infections and antibiotic-resistant bacterial colonization. Importantly, the trial excluded severely immunosuppressed patients and those with Staphylococcus aureus infections, which generally require longer treatment.1
In an exclusive interview with Nick Daneman, MD, FRCPC, MSc, one of The BALANCE trials lead investigators, he explained the trial's exclusion criteria. “We included most immunosuppressed patients, and only excluded patients with neutropenia and transplantation.” He continued, “S aureus has many surface molecules that enable it to bind to a range of tissues including bones, joints, and heart valves among others, and so it commonly causes metastatic infection. Therefore, it theoretically requires a longer duration of treatment. Observational studies suggest higher failure rates with shortened treatment. A randomized clinical trial is needed to evaluate Staphylococcus aureus treatment duration but the treatment arms would likely be longer than 7 days in such a trial.”
The shorter 7-day regimen offers both patient-level and public health benefits. Reducing antibiotic exposure could help curb antimicrobial resistance, while potentially lowering healthcare costs by avoiding prolonged treatment. Despite concerns about long-term resistance risks, Daneman pointed out that, “Our primary outcome (death at 90 days) is patient important and is a relatively long-term outcome from the onset of infection. We found a strong signal of non-inferiority of shorter duration treatment. In fact, the point estimate for 90-day death rate was lower in those receiving 7-day treatment. Therefore, we do not have concerns that shorter duration treatment could result in worse outcomes.”
The BALANCE trial found that a 7-day antibiotic regimen for bloodstream infections is as effective as the traditional 14-day course, with no significant difference in 90-day mortality.
The study demonstrated that a shorter treatment duration is viable for critically ill patients, with 55% of participants being in the ICU.
Shortening antibiotic courses can reduce healthcare costs and help combat antimicrobial resistance, aligning with broader antibiotic stewardship goals.
Regarding antimicrobial resistance, Daneman stated, “There are strong theoretical reasons why shorter duration treatment should cause less ecologic harms of antimicrobial resistance than longer duration treatment. Even though we were unable to demonstrate a reduction in resistance with shorter treatment in this study, we think it is very unlikely that resistance would be higher with reduced durations.”
Despite some non-adherence in the trial, with 23.1% of patients in the 7-day group and 10.7% in the 14-day group receiving longer treatment, Daneman provided guidance on safely implementing a 7-day regimen in practice, especially for critically ill patients. He explained, “Our results clearly indicate that a strategy of planning for 7 days of treatment is non-inferior to a strategy of committing all patients to 14 days of treatment. Some patients might require prolongation of treatment beyond 7 days, and that will require clinical judgement. However, randomization to a 7-day strategy was clearly non-inferior to a 14-day strategy even in critically ill patients enrolled in intensive care units.”
These findings align with the CDC’s focus on preventing healthcare-associated infections and minimizing unnecessary antibiotic use. As highlighted in the CDC’s 2023 National and State HAI Progress Report, healthcare-associated infections, particularly those caused by resistant bacteria like MRSA and C difficile, continue to pose significant challenges.2 Reducing unnecessary antibiotic use, as suggested by the BALANCE trial, could help mitigate the spread of resistant infections and improve patient outcomes.
In conclusion, the BALANCE trial suggests that 7-day antibiotic courses may be a viable alternative to the standard 14-day treatment for bloodstream infections, offering benefits in patient outcomes and reducing unnecessary antibiotic use. These findings support broader efforts to reduce antimicrobial resistance and improve infection prevention practices in healthcare.
