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April 2025
Shorter Antibiotic
Courses for Bacteremia?
Several small studies have suggested that shorter antibiotic courses for bacteremia are noninferior to the more standard 14-day course. Canadian researchers recently published the results of a larger study comparing 7-day vs 14-day courses of antibiotics for bacteremia (NEJM 2025).
The BALANCE trial was a multicenter, noninferiority trial that randomly assigned 3608 hospitalized patients who had bloodstream infections to receive antibiotic treatment for 7 days or 14 days. Patients with severe immunosuppression, foci requiring prolonged treatment, single cultures with possible contaminants, or cultures yielding Staphylococcus aureus were excluded. But, compared to some prior studies, patients in intensive care units were included (in fact, 55% of participants were in ICU’s). Antibiotic selection, dosing, and route were at the discretion of the treating team. The primary outcome was death from any cause by 90 days after diagnosis of the bloodstream infection, with a noninferiority margin of 4 percentage points.
75.4% of infections were acquired in the community, 13.4% on hospital wards, and 11.2% in ICU’s. Bacteremia most commonly originated from the urinary tract (42.2%), abdomen (18.8%), lung (13.0%), vascular catheters (6.3%), and skin or soft tissue (5.2%). More than 70% had gram negative bacteremia.
There are many theoretical advantages we might expect if such patients with bacteremia can be safely treated with these shorter courses of antibiotics. Reduced development of antibiotic resistance would be a potentially major benefit. But patients also might have fewer antibiotic-related side effects and might be less susceptible to developing C. diff infections. Shorter courses conceivably could also lead to shorter hospital lengths of stay and we are well aware that the risk of a patient safety event increases with each day in the hospital. However, in this study, secondary clinical outcomes including measures of length of stay, vasopressor use, and mechanical ventilation use, were similar in the two groups. Perhaps larger studies might clarify the impact of shorter courses on these theoretical advantages.
Note that the study did not include patients with Staph aureus bacteremia, which is one of the most serious types of bacteremia. Also, as pointed out in the accompanying editorial (Fowler 2025), US hospitals were underrepresented in the trial. Patients in both groups also sometimes received antibiotics for more days than they had been randomized to.
But, overall, this study is very reassuring and may well lead to a movement away from the more standard longer courses of antibiotic therapy.
References:
The BALANCE Investigators, for the Canadian Critical Care Trials Group, the Association of Medical Microbiology and Infectious Disease Canada Clinical Research Network, the Australian and New Zealand Intensive Care Society Clinical Trials Group, and the Australasian Society for Infectious Diseases Clinical Research Network. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med 2025; 392(11): 1065-1078 Published November 20, 2024
https://www.nejm.org/doi/full/10.1056/NEJMoa2404991?query=TOC
Fowler VG. Eight Days a Week — BALANCING Duration and Efficacy. N Engl J Med 2025; 392(11): 1136-1137 Published March 12, 2025
https://www.nejm.org/doi/full/10.1056/NEJMe2414037
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