The BALANCE Trial
The trial comparing 7-day versus 14-day antibiotic duration in critically ill patients with bloodstream infections is the BALANCE trial (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness). 1
Trial Design and Population
The BALANCE trial was a multicenter, noninferiority randomized controlled trial conducted across 74 hospitals in seven countries, enrolling 3,608 hospitalized patients (including ICU patients) with bloodstream infections. 1
- 55.0% of enrolled patients were in the ICU at the time of enrollment 1
- 45.0% were on hospital wards 1
- The trial excluded patients with severe immunosuppression, infections requiring prolonged treatment (such as endocarditis), single cultures with possible contaminants, or cultures yielding Staphylococcus aureus 1
Key Findings
The trial demonstrated that 7 days of antibiotic treatment was noninferior to 14 days, with 90-day mortality of 14.5% in the 7-day group versus 16.1% in the 14-day group (difference -1.6 percentage points; 95.7% CI -4.0 to 0.8). 1
- The noninferiority margin was set at 4 percentage points 1
- These findings remained consistent across secondary clinical outcomes and across prespecified subgroups defined by patient, pathogen, and syndrome characteristics 1
- Per-protocol analysis also showed noninferiority (difference -2.0 percentage points; 95% CI -4.5 to 0.6) 1
Clinical Context
This trial built upon earlier work establishing equipoise for shorter antibiotic durations in critically ill patients:
- A 2018 pilot RCT (n=115) across 11 ICUs demonstrated feasibility of comparing 7 versus 14 days of treatment for bloodstream infections in critically ill patients, achieving 77% adherence to treatment duration protocols 2
- The pilot study excluded similar patient populations (severe immunosuppression, S. aureus, fungi) and showed complete ascertainment of outcomes at 90 days 2
Relationship to Other Critical Care Antibiotic Duration Studies
While the BALANCE trial focused on bloodstream infections, other landmark trials have addressed antibiotic duration in critical care:
- For ventilator-associated pneumonia (VAP), earlier studies compared 8-day versus 15-day regimens, finding no difference in mortality (18.8% vs. 17.2%) 3
- A 2015 Cochrane review of six studies (1,088 participants) concluded that 7-8 days of antibiotics for VAP was as effective as 10-15 days, except for cases due to non-fermenting Gram-negative bacilli where recurrence was higher with short-course therapy 4