Analysis of effects of cell wall active antibiotics towards development of vancomycin non-susceptibility in methicillin-resistance Staphylococcus aureus

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Analysis of effects of cell wall active antibiotics towards development of vancomycin non-susceptibility in methicillin-resistance Staphylococcus aureus

 

Author: Lam, Ka Wai Ricky
Title: Analysis of effects of cell wall active antibiotics towards development of vancomycin non-susceptibility in methicillin-resistance Staphylococcus aureus
Degree: M.Sc.
Year: 2012
Subject: Antibiotics.
Vancomycin resistance.
Methicillin resistance.
Staphylococcus aureus.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: xii, 120 leaves : ill. (some col.) ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2551485
URI: http://theses.lib.polyu.edu.hk/handle/200/6845
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a well known pathogen associated with hospital acquired and community infection. Vancomycin is the mainstay to treat MRSA infection, but non-susceptible strains have been reported since 1997 in Japan. Although having low prevalence, these resistant strains known as vancomycin intermediate S. aureus (VISA) and heterogeneous vancomycin intermediate S. aureus (h-VISA), were a problem for treatment and laboratory detection. There are many studies explaining the features of cell wall thickening and genetic mutations of two-component regulatory system (TCRS) vraSR and graRS, associated with VISA. Thickened cell wall causes the slowing of diffusion of the vancomycin molecule to the target site. Genetic mutation stimulates cell wall synthesis and is associated with the increase of vancomycin minimum inhibitory concentration. In this study, vancomycin non-susceptible S. aureus were induced under selection using a variety of cell wall active antibiotics. Sequencing of vraS and graR genes were compared with their susceptible parent strains for genome analysis. From the results, all antimicrobial agents used (vancomycin, cefotaxime, rifampin and ciprofloxacin) were found to show induced effect to vancomycin non-susceptibility. Non-cell wall active agent, Ciprofloxacin was found to show the lowest effect on vancomycin non-susceptibility and did not induce a VISA phenotype. Additionally, there was no significant change of Bacitracin susceptibility results demonstrated by all drug induced strains. Finally, we have identified vraS and graR mutations in the sequence of derived strains, respectively, were found to be associated with the development of vancomycin non-susceptibility in methicillin-resistance S. aureus. This suggests combine effect of vancomycin and other groups of antimicrobial agents have low likelihood to combat against MRSA infection.

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