Clinical tools for the prediction of antimicrobial resistance have been derived and validated without examination of their implementation in clinical practice. This study examined the impact of utilization of the extended-spectrum beta-lactamase (ESBL) prediction score on the time to initiation of appropriate antimicrobial therapy for bloodstream infection (BSI). The quasi-experimental cohort study included hospitalized adults with BSI due to ceftriaxone-resistant (CRO-R)Enterobacteralesat three community hospitals in Columbia, South Carolina, USA before (January 2010 to December 2013) and after (January 2014 to December 2019) implementation of an antimicrobial stewardship intervention. In total, 45 and 101 patients with BSI due to CRO-REnterobacteraleswere included before and after the intervention, respectively. Overall, the median age was 66 years, 85 (58%) were men, and 86 (59%) had a urinary source of infection. The mean time to appropriate antimicrobial therapy was 78 h before and 46 h after implementation of the antimicrobial stewardship intervention (p= 0.04). Application of the ESBL prediction score as part of an antimicrobial stewardship intervention was associated with a significant reduction in time to appropriate antimicrobial therapy in patients with BSI due to CRO-REnterobacterales. Utilization of advanced rapid diagnostics may be necessary for a further reduction in time to appropriate antimicrobial therapy in this population.