Staphylococcus aureus infections in New Zealand: A clinical and molecular epidemiological study

Abstract

Staphylococcus aureus is the leading bacterial cause of morbidity and mortality in New Zealand. Diseases caused by S. aureus range from extremely common, relatively minor skin and soft tissue infections such as folliculitis and impetigo (school sores), through to less common, but potentially life threatening infections, such as osteomyelitis and endocarditis. This thesis describes the epidemiology of skin infections caused by S. aureus in New Zealand, with particular emphasis on the relationships between ethnicity and the incidence of disease. It also outlines the recent evolution of S. aureus in New Zealand, focusing on the emergence and dissemination of methicillin resistant S. aureus (MRSA) clones, and clones resistant to topical antimicrobials. In summary, the thesis provides a contemporary overview of key aspects of S. aureus skin disease in New Zealand. The first part of the thesis systematically describes the epidemiology of S. aureus disease in New Zealand, and focuses on a significant increase in S. aureus skin infections, with the greatest burden of disease in Māori and Pacific children. The second part of the thesis examines the possible microbiological reasons for the high rates of S. aureus skin infections in Māori and Pacific children, with particular focus on the prevalence of S. aureus colonisation, and the S. aureus clonal complexes circulating in this demographic group. This work demonstrates that the prevalence of S. aureus colonisation in Māori and Pacific children in Auckland, and the S. aureus clonal complexes that colonise these children, are similar to those found in other parts of the world. However, the thesis documents (i) the high rate of fusidic acid resistance in S. aureus isolates, particularly from Māori and Pacific children, and (ii) the emergence of a fusidic acid-resistant, methicillin-resistant sequence type 5 (ST5) S. aureus clone, which has swept aside other major MRSA clones to become the dominant MRSA in New Zealand. Finally, the thesis explores the possible reasons for the high rate of fusidic acid resistance in S. aureus in New Zealand. This work points to the significant increase in topical fusidic acid usage in New Zealand, particularly in Māori and Pacific children, as the likely cause of a concurrent increase in fusidic acid resistance, due to the emergence of fusidic acid-resistant S. aureus clones. Genomic analysis of the dominant methicillin susceptible CC1 clone and the methicillin resistant CC5 clone demonstrates the presence of mobile genetic elements harbouring the acquired fusC gene, with considerable genetic similarity between these elements across different S. aureus clones. Of most concern is the co-location of the fusC gene and the mecA gene (responsible for methicillin resistance) on the same mobile genetic elements, meaning that selection of fusidic acid resistant strains by high population usage of this topical antimicrobial was likely also co-selecting for MRSA. This work therefore provides an underlying genomic explanation for the dramatic emergence of fusidic acid-resistant ST5 MRSA in New Zealand over the past decade.