Clinical question: Is a seven-day course of antibiotics noninferior to a 14-day course for adults with Gram-negative bloodstream infections?
Background: Traditionally, the standard duration of therapy for Gram-negative bacteremia has been 14 days. However, recent randomized trials suggest shorter courses may be sufficient and could reduce adverse effects, antimicrobial resistance, and complications associated with prolonged antibiotic use.
Study design: Systematic review and Bayesian meta-analysis of randomized controlled trials
Setting: Multicenter randomized trials conducted in hospitals in Israel, Italy, Switzerland, Spain, Canada, Australia, New Zealand, Saudi Arabia, and the U.S.
Synopsis: This systematic review and meta-analysis included four randomized controlled trials with 3,729 adults hospitalized with Gram-negative bloodstream infections randomized to receive either seven or 14 days of antibiotics. Most infections were caused by Enterobacterales species, and urinary sources were common.
In the intention-to-treat analysis, the risk ratio (RR) for 90-day mortality with seven versus 14 days of therapy was 0.91 (95% credible interval [CrI], 0.69–1.22), corresponding to a 97.8% probability of noninferiority using a predefined margin of RR up to 1.25. In the per-protocol analysis, the RR was 0.93 (95% CrI, 0.68–1.32), with a 95.1% probability of noninferiority. Mortality occurred in 12.0% of the seven-day group and 13.7% of the 14-day group. Evidence certainty was graded as high. Limitations include the small number of trials, underrepresentation of immunocompromised patients, and predominance of Enterobacterales infections.
Bottom line: Seven days of antibiotics is likely noninferior to 14 days for uncomplicated Gram-negative bloodstream infections with adequate source control.
Citation: Lee TC, et al. Seven vs fourteen days of antibiotics for Gram-Negative bloodstream infection: a systematic review and noninferiority meta-analysis. JAMA Netw Open. 2025;8(3):e251421. doi:10.1001/jamanetworkopen.2025.1421.
Dr. Chatterjee
Dr. Chatterjee is a hospitalist and associate professor of internal medicine and pediatrics at the University of North Carolina in Chapel Hill, N.C.