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Title: The pathogenesis of methicillin resistant staphylococcus aureus infection
Author: Alshami, Issam Abdulla
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2003
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Outbreaks with strains of methicillin resistant Staphylococcus aureus (MRSA) began in a London hospital in 1982 and continue to be associated with significant morbidity and mortality. These particular strains, termed epidemic methicillin resistant S. aureus (EMRSA), are recognised by their phage type and antibiogram. This study examined the ability of isolates representing EMRSA strains recovered from different outbreaks in England and Wales (EMRSA 1-16) to grow in escalating levels of vancomycin. A series of the EMRSA strains were subjected to passage-selection in vancomycin. Six strains became vancomycin resistant, three became vancomycin intermediate, and seven remained susceptible, which confirmed that EMRSA strains were able to develop resistance to vancomycin in vitro. The vancomycin MICs for the vancomycin-resistant derivatives ranged from 24 -32 ug/ml, were associated with decreased lysostaphin susceptibilities and increased cell wall thickness. The MICs of teicoplanin was also increased. Five of the six vancomycin-resistant derivatives became susceptible to methicillin with instability of the S. aureus mecA gene. There were no significant changes to other antimicrobial agents susceptibility, including Linezolid. During this study an attempt was made to elucidate the development of resistance to vancomycin by studying the heterogeneous phenotype of resistance. Population analysis profiles for the vancomycin-resistant derivatives demonstrated that four of them expressed a heterogeneous subpopulation. Bacteriophage typing failed to type vancomycin-resistant clones, while Pulsed-field gel electrophoresis (PFGE) gave good discrimination. In conclusion, we found that, although vancomycin is usually bactericidal against S. aureus, resistance can be common amongst MRSA isolates. Decreased susceptibility to vancomycin appeared to be a selective or inducible process that increased during persistent sublethal exposure to vancomycin. Thus, if this effect occurs in vivo, then not only is vancomycin therapy of serious EMRSA infection compromised, but the propensity to develop resistance may remain undetected by standard laboratory sensitivity testing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available