|Author:||Chan, Sze-yeung Anthony|
|Title:||Can resistance develop in further vancomycin exposure of previously vancomycin non-susceptible strains which have reverted to susceptible?|
Hong Kong Polytechnic University -- Dissertations
|Department:||Department of Health Technology and Informatics|
|Pages:||81 leaves : ill. ; 30 cm.|
|Abstract:||MRSA is a common pathogen associated with nosocomial and community acquired infections⁽⁹⁾. To treat MRSA, vancomycin remains the drug of choice. Since the first report of VISA/hVISA in Japan in 1997⁽³⁰⁾, the prevalence of reduced vancomycin susceptibility is increasing worldwide. Vancomycin treatment failure has become a problem in medical communities⁽²¹⁾. Vancomycin inhibits cell wall synthesis in Staphylococcus aureus. Cell wall thickening is a major feature of VISA, the thickened cell wall slow down the diffusion of vancomycin molecule to its active site in the cytoplasmic membrane of division septum resulting in decreased potency of the vancomycin. ⁽¹⁸⁾ The two component system, vraSR and graSR, has been associated with glycopeptide resistance in MRSA. Over-expression of vraSR and graSR increases cell wall thickness and raises the vancomycin MIC. Single point mutations in vraSR and graSR genes may contribute to cell wall thickening and loss of vancomycin susceptibility⁽⁶' ⁸' ¹⁴⁾. In this project, six strains of MRSA previously induced to VISA which had reverted to VSSA were exposed to vancomycin again. The MIC trend was monitored and the genetic changes in vraS and graR gene during development and loss of vancomycin non susceptibility were tracked. Results showed that these VSSA strains can be induced to VISA or resistant strain again when re-exposed to vancomycin. Genetic analysis revealed that several mutations caused amino acids change and presence of stop codon in vraS and graR gene during development and loss of vancomycin non susceptibility. All these results suggested that to prevent treatment failure, it is important to monitor the MIC changes during vancomycin therapy.|
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