Time to Effective Antibiotic Therapy and Clinical Outcomes in Bloodstream Infections With ESBL-Producing Enterobacterales: A Retrospective Multicenter Cohort Study

Abstract

Abstract Background Patients with bloodstream infections (BSIs) with antimicrobial resistant bacteria often receive ineffective empirical therapy (IET). The implications are still uncertain. Methods We performed a retrospective, multicenter, study of patients with BSIs caused by extended-spectrum β-lactamase (ESBL)-producing gram-negative bacteria in southern Sweden from 2013 to 2022. Patients were categorized based on time to effective therapy: ≤24 hours (EET) and >24 hours (IET). Therapy was considered effective if the agent was active in susceptibility testing and administered intravenously at an appropriate dose. The primary outcome was 30-day mortality. Secondary outcomes were ICU admission and hospital length of stay. Results A total of 289/644 (44.9%) patients received IET within the first 24 hours after the index blood culture collection. No significant impact of IET on 30-day mortality was found in univariable (Hazard ratio 0.66; P = .15) or multivariable Cox regression analysis (Hazard ratio 0.64; P = .13). Patients receiving EET were more likely to receive intensive care (Odds ratio 0.38; P = .008), but the association was nonsignificant after adjusting for severity of illness and comorbidities. IET was not associated with a longer hospital stay in Fine–Gray competing risks regression analysis (univariable: sHR 1.15; P = .082; multivariable: sHR 1.11; P = .20). Conclusions IET was not associated with 30-day mortality, in patients with BSIs with ESBL-producing Enterobacterales. If confirmed in prospective studies, our findings could support antimicrobial stewardship efforts by reducing unnecessary empirical carbapenem use without compromising short-term clinical outcomes, particularly in low-prevalence settings.