Original Investigation
Fast Antimicrobial Susceptibility Testing for Gram-Negative Bacteremia: The FAST Randomized Clinical Trial
Ritu Banerjee, Lauren Komarow, Yixuan Li, et al
JAMA Published Online: April 18, 2026
doi: 10.1001/jama.2026.5487
Key Points
Question Does use of rapid antimicrobial susceptibility testing directly from blood culture bottles positive for gram-negative bacteria improve clinical outcomes compared with standard care?
Findings In this randomized clinical trial of 850 patients with gram-negative bloodstream infections performed in 4 countries with high levels of antimicrobial resistance, the probability of a more desirable outcome at day 30 in the rapid blood culture antimicrobial susceptibility testing group compared with the standard testing group was 48.8%, which did not achieve the prespecified criterion for superiority.
Meaning Rapid blood culture antimicrobial susceptibility testing for gram-negative bacteremia was not superior to standard testing in achieving a more desirable outcome at day 30.
Importance Novel blood culture diagnostics provide rapid antimicrobial susceptibility testing (AST) results for bacteria causing bloodstream infections (BSIs) but have unclear clinical impact.
Objective To evaluate clinical outcomes of blood culture testing using a rapid AST method compared with standard AST in patients with BSIs caused by gram-negative bacilli in regions with high prevalence of antimicrobial resistance.
Design, Setting, and Participants Open-label randomized clinical trial that enrolled participants from December 2023 to May 2025 (final follow-up, June 18, 2025) at 7 medical centers in Greece (n = 2), India (n = 1), Israel (n = 3), and Spain (n = 1). Hospitalized patients (adults and children) with BSIs caused by gram-negative bacilli were eligible. Statistical analysis was conducted from August 2025 to January 2026.
Intervention Patients were randomized to undergo blood culture evaluation using rapid, phenotypic AST directly from positive blood cultures plus standard susceptibility testing (n = 413) vs standard susceptibility testing alone (n = 437). Local antimicrobial stewardship teams reviewed all patients and provided treatment recommendations.
Main Outcomes and Measures The primary outcome was a desirability of outcome ranking (DOOR) at day 30, with 3 categories (alive without deleterious events, alive with deleterious events, and death). The difference between rapid and standard testing was summarized as the probability that the DOOR outcomes were more desirable in the rapid testing group. Superiority was concluded if the lower limit of the 95% CI exceeded 50%. Secondary outcomes included 30-day mortality, length of hospitalization, intensive care unit admission, acquisition of hospital-acquired infections, time to effective antibiotic therapy within 3 days, and time to antibiotic escalation or deescalation within 3 days.
Results Of the 899 patients randomized, 850 were included in the primary outcome analysis (median [IQR] age, 72 [21] years; 43% female). The probability that DOOR outcomes were more favorable in the rapid testing group was 48.8% (95% CI, 45.3%-52.4%). Median time to effective antibiotic therapy was not different between the groups in the as-randomized population. Median time to antibiotic escalation or deescalation was faster in the rapid testing group by 14 hours (95% CI, 6-22) in the as-randomized population. There were no differences between the groups in other secondary outcomes. In the prespecified subgroup with carbapenem-resistant infections, median time to effective therapy was 9.5 hours in the rapid testing group vs 28 hours in the standard testing group (difference, −18 hours [95% CI, −42 to 6]).
Conclusions and Relevance Among patients with gram-negative bacilli BSIs, rapid blood culture AST was not superior to standard testing by DOOR. When considered with other efficacy and safety outcomes, these findings may help inform the use of rapid susceptibility testing in clinical practice.
Trial Registration ClinicalTrials.gov Identifier: NCT06174649
