Very Early Transition to Oral Antibiotics in Uncomplicated Enterobacterales Bloodstream Infections: Effectiveness and Impact on Carbon Footprint Saving

<b>Background/Objective</b>: This study aimed to evaluate the effectiveness of very early oral transition in Enterobacterales bloodstream infections (E-BSIs), identify factors associated with it, compare the effectiveness of different oral options, and assess its economic and ecological benefits. <b>Methods</b>: Retrospective, observational cohort study including monomicrobial E-BSI in clinically stable adult patients by day 3 of bacteremia with oral antibiotic options. Transition to oral antibiotics by day 3 or earlier (early oral (EO) group) was compared to later transition or remaining on intravenous therapy (nEO group). Early oral transition-associated factors were analyzed. Oral high-dose beta-lactams (BLs) were compared to quinolones (QLs) or trimethoprim/sulfamethoxazole (TS). Economic and ecological costs were assessed. <b>Results</b>: Of 345 E-BSI, 163 (47.2%) were in the EO group, characterized by more urinary tract infections (UTIs) and shorter hospital stays. The nEO group had higher Charlson Comorbidity Index (CCI), extended-spectrum beta-lactamase (ESBL) production, greater source control need, and longer time to clinical stability. There were no significant differences in mortality and relapse. UTIs were associated with early oral transition (OR 2.02, IC 95% 1.18-3.48), while higher CCI (0.85, 0.77-0.95), source control need (0.39, 0.19-0.85), longer time to clinical stability (0.51, 0.39-0.66), and ESBL isolates (0.39, 0.19-0.80) hindered this practice. High-dose BLs and QL/TS were equally effective. Early oral transition resulted in 38.794 KgCO₂eq reduction and EUR 269,557.99 savings. <b>Conclusions</b>: Very early oral transition at day 3 or before in stable E-BSI patients is effective, eco-sustainable, and cost-effective; UTI is related with the early oral switch, while comorbidities, ESBL production, source control need, or longer time to clinical stability hinder this practice.