Multiple hypervirulent methicillin-sensitive Staphylococcus aureus lineages contribute towards poor patient outcomes in orthopedic device-related infections

Staphylococci are the most common cause of orthopedic device-related infections (ODRIs), with Staphylococcus aureus responsible for a third or more of cases. This prospective clinical and laboratory study investigated the association of genomic and phenotypic variation with treatment outcomes in ODRI isolates. Eighty-six invasive S. aureus isolates were collected from patients with ODRI, and clinical outcome was assessed after a follow-up examination of 24 months. Each patient was then considered to have been "cured" or "not cured" based on predefined clinical criteria. Whole genome sequencing and molecular characterization identified isolates belonging to globally circulating community- and hospital-acquired pandemic lineages. Most isolates were phenotypically susceptible to methicillin and lacked the SCCmec cassette (MSSA), but contained several (hyper) virulence genes, including toxins and biofilm genes. While recognizing the role of the host immune response, we identify characteristics of isolate genomes that, with larger datasets, could help contribute to infection severity or clinical outcome predictions. While this and several other studies reinforce the role antibiotic resistance (e.g., MRSA infection) has on treatment failure, it is important not to overlook MSSA that can cause equally destructive infections and lead to poor patient outcomes. ImportanceStaphylococcus aureus is a prominent cause of orthopedic device-associated infections, yet little is known about how the infecting pathogen, and specifically the repertoire of genome-encoded virulence factors can impact treatment outcome. Past studies have focused on distinguishing commensal from invasive S. aureus isolates but in this study, we aim to investigate traits in infecting isolates that influence patient outcomes. Invasive S. aureus isolates were collected from orthopedic-device related infection patients and categorized according to the success of subsequent treatment ("cured" /"not cured"), as determined following hospital discharge two years after initial presentation. Several MSSA hypervirulent clones were associated with a "not cured" clinical outcome. Improved understanding of the bacterial traits associated with treatment failure in ODRI will inform the risk assessment, prognosis, and therapy of these infections.