Antibiotic Treatment for 7 days is Noninferior to 14 days in Patients with Uncomplicated Bacteremia

Clinical question: Is seven days of antibiotic treatment for bloodstream infections noninferior to 14 days of treatment?

Background: Bloodstream infections are very common, can originate from a variety of infectious foci, and are highly lethal. Randomized controlled trials have shown that shorter courses of antibiotics for infections such as pneumonia, pyelonephritis, and cellulitis are noninferior compared to longer durations of treatment. However, these results cannot be extrapolated to the treatment of bacteremia due to prior exclusion criteria or the limited size of the studies. Therefore, the treatment duration of bacteremia remains highly variable. 

Study design: Multicenter, randomized, controlled, noninferiority study

Setting: 74 hospitals across Australia, Canada, Israel, Saudi Arabia, New Zealand, Switzerland, and the U.S.

Synopsis: The study enrolled 3,608 hospitalized patients with a positive blood culture during admission and randomized them to seven or 14 days of antibiotic treatment. Exclusion criteria included severely immunocompromised status, presence of prosthetic heart valves or endovascular grafts, infections requiring prolonged treatment (e.g., endocarditis, osteomyelitis), Staphylococcus aureus and Staphylococcus lugdunensis bacteremia, and fungemia. Clinicians determined the antibiotic selection, dose, and method of delivery. The primary outcome was all-cause mortality 90 days after bacteremia diagnosis, with a non-inferiority margin of 4%. Intention-to-treat analysis found that seven days of treatment was non-inferior to 14 days (difference, –1.6%; confidence interval [CI], -4.0 to 0.8). There were no significant differences in the secondary outcomes regarding death in intensive care (-0.6%; CI, –3.2 to 1.9), death in the hospital (-1.0%; CI, -2.9 to 0.9), or relapsed bacteremia (0.4%; CI, –0.6 to 1.4).

Limitations of this work include the inability of noninferiority trials to prove identical outcomes between groups. Additionally, this study was underpowered to assess whether the longer course of antibiotics would confer a potential benefit to subgroups.

Bottom line: In hospitalized patients with uncomplicated bloodstream infections with important exclusions (e.g., S. aureus, S. lugdunensis, and fungemia), a clinician-driven strategy of seven days of antibiotic treatment is non-inferior to 14 days of treatment.

Citation: Daneman N, et al; Antibiotic treatment for 7 versus 14 days in patients with bloodstream infections. N Engl J Med. 2025;392(11):1065-1078. doi: 10.1056/NEJMoa2404991.

Dr. Tsui is a fourth-year resident in internal medicine and pediatrics at Maine Medical Center-Tufts University School of Medicine in Portland, Maine.