TL;DR: 🟢 Positive (noninferiority) — 7-day antibiotics were noninferior to 14 days for bloodstream infections (90-day mortality 14.5% vs 16.1%), point estimate favored the shorter course.
1. Publication
- Title: Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections
- Acronym: BALANCE
- Year & Journal: New England Journal of Medicine, published November 20, 2024 (print: 2025;392:1065-1078)
- Citation: The BALANCE Investigators, for the Canadian Critical Care Trials Group et al. N Engl J Med. 2025;392:1065-1078. doi:10.1056/NEJMoa2404991
2. Context & Rationale
Background: Bloodstream infections (BSI) carry substantial morbidity/mortality; early appropriate antibiotics are essential but optimal duration was uncertain, with 14-day courses conventional despite limited evidence.
Research Question/Hypothesis: In hospitalized patients (including ICU) with BSI, is 7 days of antibiotic treatment noninferior to 14 days with respect to 90-day all-cause mortality?
3. Design & Methods
- Study Type: Multicenter, noninferiority RCT
- Setting & Centers: 74 hospitals, 7 countries (Canadian Critical Care Trials Group, AMMI Canada, ANZICS CTG, Australasian Society for Infectious Diseases)
- Population: Hospitalized patients (ward and ICU) with bloodstream infection
- Intervention: 7 days of antibiotic treatment (agent/dosing/route at treating team discretion)
- Comparator: 14 days of antibiotic treatment
- Randomization: 3608 patients
- Statistical Power & Follow-Up: Primary: death from any cause by 90 days; noninferiority margin 4 percentage points.
4. Key Results
3608 patients across 74 hospitals.
Outcome | 7-Day Treatment | 14-Day Treatment | Effect Size | 95% CI | Notes |
90-day all-cause mortality (primary) | 14.5% | 16.1% | Diff −1.6pp | 95.7% CI −4 to 0.8 | Noninferiority met; point estimate favored shorter course |
5. Internal Validity Assessment
Large (3608-patient), multinational, well-conducted noninferiority trial with appropriate margin. Overall: Strong — the point estimate for 90-day mortality actually favored the shorter course, providing reassurance rather than borderline noninferiority.
6. External Validity Assessment
Broad, multinational (7-country), mixed ward/ICU BSI population — among the most generalizable antibiotic-duration trials to date, though not powered to examine specific BSI sources separately.
7. Strengths & Limitations
Strengths: Large, multinational, well-executed noninferiority design; inclusion of both ward and ICU patients increases generalizability; clear, statistically robust result.
Limitations: Not powered for BSI-source-specific subgroup analysis; heterogeneous population (ward inclusion increases generalizability but also case-mix heterogeneity).
8. Interpretation & Practice Impact
Supports 7-day antibiotic courses as sufficient for most bloodstream infections — reducing healthcare costs, antibiotic exposure, and resistance risk without compromising survival.
9. Controversies & Subsequent Evidence
Aligns directly with ADAPT-Sepsis (this handbook) in supporting shorter antibiotic courses; together the two trials represent a significant 2024 evidence push toward antimicrobial stewardship through duration reduction rather than agent selection alone.
10. Summary & Executive Takeaway
Summary: BALANCE randomized 3608 hospitalized patients with bloodstream infection across 74 hospitals in 7 countries to 7 or 14 days of antibiotics. 90-day mortality was 14.5% vs 16.1% (noninferiority met, margin 4pp).
Overall Takeaway: A 7-day antibiotic course is sufficient for most bloodstream infections — a well-powered, generalizable trial supporting shorter-duration therapy as a default antimicrobial stewardship strategy.
11. Bibliography
- ADAPT-Sepsis Collaborators. Biomarker-Guided Antibiotic Duration for Suspected Sepsis. JAMA 2024 (this handbook).