Molecular Epidemiology of Staphylococcus aureus and Newer Treatment Strategies

Abstract

Staphylococcus aureus stands out as the most prevalent bacteria causing bloodstream infection (BSI). This formidable pathogen demonstrates its severity by claiming the lives of over one in four individuals within three months of a BSI. S. aureus includes penicillin-susceptible S. aureus (PSSA), methicillin-susceptible S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA). These strains exhibit differences in geographic distribution, molecular epidemiology, and antibiotic susceptibility. Despite these distinctions, all three variants induce a comparable spectrum of illness and share a similar fatality rate in cases of BSI.

Bacterial typing of both MSSA and MRSA has revealed the presence of numerous sub-clones. Notably, MSSA exhibits a more diverse clonal population compared to MRSA. The predominant clones may vary from country to country, but successful clones have demonstrated the capacity to spread internationally.

Over the past 10-15 years, the epidemiology of S. aureus has undergone significant changes. MRSA rates have declined, while the proportion of S. aureus isolated from blood cultures identified as PSSA has increased. Despite these changes, the case fatality rates in S. aureus BSI have not altered. The disease continues to pose a significant threat and remains deadly.

We hypothesised that monitoring S. aureus in both sterile and non-sterile sites could offer insights into their population dynamics. Our aim was to identify potential hospital-acquired (HA) MSSA clones in the same way that there are particular clones of MRSA that are associated with hospital acquisition (HA-MRSA). By gaining a more comprehensive understanding of S. aureus epidemiology, carriage patterns, and pathogenesis, our goal was to identify potential therapeutic gaps. These findings could then be explored further to improve treatment outcomes.

This thesis is presented as a combination of published papers (Chapters 4, 5, 9, and 10) and unpublished work (Chapters 1-3, and 6-8).