Factors Associated with Methicillin-Resistant Staphylococcus aureus Infection Among Patients with Sepsis Presenting to Emergency Departments: A Nationwide Multicenter Cohort Study

Background/Objectives: Prompt initiation of appropriate antibiotics is essential for sepsis management. While early anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy benefits confirmed cases, unnecessary use in low-risk patients promotes antimicrobial resistance. Current guidelines recommend risk-based empiric coverage, but specific predictors in the emergency department (ED) remain poorly defined. Therefore, this study aims to identify clinical factors independently associated with MRSA infection in ED patients with sepsis. Methods: This retrospective analysis used data from a prospective, nationwide, multicenter cohort in the Korean Sepsis Alliance registry. The study included 11,477 adults with sepsis from 16 tertiary or university-affiliated EDs between September 2019 and December 2022. Factors independently associated with MRSA infection were identified with multivariable logistic regression. Results: MRSA infection occurred in 189 of 11,477 patients (1.65%; 95% confidence interval [CI], 1.43–1.90%), representing 2.86% (95% CI, 2.49–3.29%) of patients with a microbiologically identified causative pathogen. Catheter-related infection showed the strongest association (odds ratio [OR], 5.98; 95% CI, 1.93–18.49). Other factors independently associated with MRSA included hospitalization within 90 days (OR, 1.65; 95% CI, 1.14–2.39) and elevated C-reactive protein ≥ 6 mg/dL (data-derived cutoff; OR, 2.18; 95% CI, 1.43–3.38). Conversely, abdominal (OR, 0.19; 95% CI, 0.09–0.43) and urinary (OR, 0.40; 95% CI, 0.21–0.77) sources were linked to significantly lower risk. Conclusions: MRSA infection was uncommon (1.65%) among ED patients with sepsis. Catheter-related infection was most strongly associated with MRSA, whereas abdominal and urinary sources were associated with lower odds. These findings may help inform risk stratification and support antimicrobial stewardship in the ED.