Seven versus fourteen days for resistant bloodstream infections: what do we actually know? A scoping review

Recent randomized trials have established that 7 days of antibiotic therapy is noninferior to 14 days for bloodstream infections (BSI) caused by susceptible organisms. Whether this conclusion extends to BSI caused by resistant pathogens is unclear. We aimed to map the available evidence on antibiotic duration for resistant BSI, by resistance category, and to identify the gaps that must be addressed before shorter courses can be recommended in this setting.

This scoping review was conducted following the Arksey and O'Malley framework and reported according to PRISMA-ScR guidelines. A search of PubMed was conducted through February 2026. We included RCTs, meta-analyses, and observational studies comparing antibiotic durations for BSI. Evidence was mapped across five resistance categories: ESBL-producing Enterobacterales, carbapenemase-producing Enterobacterales (CPE), MRSA, VRE, and MDR non-fermenting Gram-negatives.

We included 28 studies: 6 RCTs (5,182 patients, including the BALANCE pilot), 6 independent meta-analyses, 15 observational studies, and 1 post-hoc subgroup analysis of the BALANCE trial. All four definitive RCTs and all six meta-analyses confirmed noninferiority of 7-day therapy for susceptible BSI; none performed a resistance-stratified subgroup analysis for multidrug-resistant organisms (MROs). The only MRO-specific RCT (OPTIMISE, 2024) was halted after enrolling 103 of 382 planned patients. Observational data-including Le Berre et al. (379 ESBL-E BSI in ICU) (Le Berre et al. in Antibiotics (Basel) 14, 2025), Soto et al. (183 CRE BSI) (Soto et al. in Clin Infect Dis 78:27-30, 2024), Bahrs et al. (219 VRE BSI) (Bahrs et al. in Clin Microbiol Infect 29:200-207, 2023), and Gajdos et al. (EUROBACT-2, 550 hospital-acquired BSI) (Gajdos et al. in Intensive Care Med 51:518-528, 2025)-were consistent with no excess harm from shorter courses but were individually underpowered for noninferiority. For each of the five pre-specified resistance categories, evidence was either absent, insufficient for subgroup analysis, or derived from underpowered observational studies.

Current RCT and meta-analytic evidence consistently supports the noninferiority of 7-day therapy for uncomplicated BSI caused by susceptible organisms. For resistant BSI, preliminary observational data are reassuring but far from definitive. Resistance-stratified trials are needed; the BALANCE + platform and SHORTEN-2 trial offer the most promising paths forward.