552. Within-Host Evaluation of Colonization During Active Methicillin-Resistant S. aureus Bacteremia

Abstract Background Staphylococcus aureus is a common commensal pathogen and a frequent cause of bacteremia, with nasal and blood isolates from single patients matching >80% of the time. Based on our prior work on paired single-patient isolates,1 our aim was to collect a contemporary set of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections (BSIs), evaluate the within-host diversity by whole-genome sequencing (WGS), and detail the clinical features linked to colonization. Methods Adult patients with MRSA BSIs were screened for MRSA in the anterior nares from July 2018 to March 2019. Blood isolates underwent WGS, and spa and agr function screens were performed on three unique nasal isolates per patient. Clinical data from the electronic medical records underwent uni- and multivariate analyses on clinical features and outcomes. Results Of 55 unique patients with MRSA BSIs, screening of 45 subjects revealed that 67% were colonized with MRSA. The majority (64%) were males, 32% had prior colonization, and the most common infection sources were vascular access (27%), skin (24%), and unknown (24%). For those with nasal colonization, blood isolates were composed of 57% clonal complex (CC)5/t002, 33% CC8/t008, and 10% other. 81% of nasal isolates matched the blood, with 20% of nasal isolates harboring diverse spa types and 23% carried agr mutants. During this time frame, WGS found one transmission event involving a colonized subject. Colonization was associated with male gender (OR=4.52 95% CI [1.05–19.49]; P = 0.04) and prior hospital admission within the last 3 months (OR=6.12 95% CI [1.44–26.09]; P = 0.01) in multivariate analysis, with no differences in outcomes. Conclusion Colonization is an important component of invasive MRSA disease, and we found high rates of colonization with a predominance of the CC5. We also noted significant diversity and high proportion of agr mutants. At-risk groups included males and those with prior hospitalization. Combined molecular and clinical analyses can define the intrahost and interhost transmission dynamics of MRSA, and enables the development of targeted approaches in order to curtail disease. 1. Altman, D. R. et al. Genome Plasticity of agr-defective Staphylococcus aureus during clinical infection. Infect. Immun.(2018). Disclosures All authors: No reported disclosures.