| Summary: | 博士 === 長庚大學 === 臨床醫學研究所 === 96 === The worldwide emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains harboring a small staphylococcal cassette chromosome mec (SCCmec) element (type IV or V) and Panton-Valentine leukocidin (PVL) genes was one of the major concerns of S. aureus in the past decade. CA-MRSA was a group of evolutionally successful strains which replicated faster and appeared to be more virulent than did hospital-acquired (HA)-MRSA. In this thesis, we conducted related studies on children which clearly delineated the clinical features and molecular epidemiology of CA-MRSA diseases in northern Taiwan. MRSA was colonized in a substantial proportion of healthy children and accounted for greater than 50% of childhood CA S. aureus infections. Longitudinal study further demonstrated that the replacement of HA-MRSA strains with the CA-MRSA strains in a teaching hospital. Compared with those reported from the US and other countries, the CA isolates in northern Taiwan carried a type IV or VT SCCmec and were of multi-drug resistance. Skin and soft tissue remained the most common manifestations. Systemic infections involving bloodstream, bone/joint and lung were not uncommon and may resulted in death. Based on these findings, we suggested that the current strategy for the management of putative CA-S. aureus infections in Taiwan should be stratified according to the site and severity of disease entity and glycopeptides and/or linezolid should be used empirically in invasive or deep-seated infections.
Molecular evidences suggested that there were two major clones of CA-MRSA circulating in northern Taiwan. Both clones were belonged to sequence type (ST) 59 and carried PVL and SCCmec IV or VT in distinct frequencies. The genotype D carrying SCCmec VT and positive for PVL was more frequently identified in clinical isolates whereas genotype C carrying SCCmec IV and negative for PVL was more commonly associated with colonizing isolates. Comparative genomic study using microarray revealed that a bacteriophage (øSa3) carrying sak gene encoding staphylokinase may contributed to the greater colonizing ability of genotype C isolates. Conversely, the production of PVL and a group of novel virulence peptides, the phenol-soluble modulin (PSM), may explain in part the virulence of genotype D isolates. A further functional study is needed to explore the roles of øSa3 bacteriophage in CA-MRSA colonization and PVL and PSM in the pathogenesis of CA-MRSA diseases.
|
|---|
