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Background Guidelines recommend immediate empiric broad-spectrum antibiotics for all patients with suspected sepsis. Understanding the epidemiology of antibiotic-resistant pathogens and empiric treatment patterns in sepsis could inform improvements in antibiotic utilization and outcomes. Methods We identified adults admitted during 2009–2015 to 104 US hospitals in the Cerner HealthFacts dataset who met CDC Adult Sepsis Event criteria and had positive clinical cultures within 2 days of admission. We characterized prevalence and empiric treatment rates for methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococcus (VRE), ceftriaxone-resistant Gram-negative organisms (CRO) (including P. aeruginosa), and extended-spectrum β-lactamase Gram-negative organisms (ESBL). We evaluated associations between in-hospital mortality and either inappropriate empiric therapy (antibiotics inactive against any isolated pathogen) or excessively broad therapy (empiric MRSA or VRE coverage, extended spectrum β-lactam, or carbapenem therapy when targeted organisms were absent), adjusting for baseline characteristics and severity-of-illness. Results The cohort included 17,962 patients with culture-positive sepsis; 2,965 (16.5%) died in-hospital. The most common culture-positive sites were urine (51.2%), blood (41.8%), and respiratory (16.5%). The most common pathogens were E. coli (33.0%), S. aureus (20.9%), and Streptococcus (13.2%) (Figure 1). Most (81.6%) patients received empiric antibiotics active against all isolated pathogens. Empiric therapy was directed at resistant organisms in 67.5% of cases (primarily vancomycin and extended spectrum β-lactams, Figure 2), but resistant organisms were isolated in only 25.2% (MRSA 11.5%, CRO 12.9%, VRE 2.0%, ESBL 0.8%). Both inappropriate empiric therapy and excessively broad empiric therapy were associated with higher mortality on multivariate analysis (OR 1.30, 95% CI 1.14–1.48 and OR 1.20, 95% CI 1.05–1.38, respectively). Conclusion Most patients with community-onset sepsis do not have resistant pathogens, yet empiric broad-spectrum antibiotics are frequently prescribed. Both inappropriate empiric therapy and excessively broad therapy are associated with worse outcomes. Disclosures All authors: No reported disclosures.

2297. Epidemiology of Antibiotic-resistant Pathogens and Empiric Treatment Patterns in Community-Onset Sepsis