Determination of fluoroquinolone MICs by spiral gradient endpoint technique and assessment of effects of an efflux pump inhibitor on MICs of resistant strains

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Determination of fluoroquinolone MICs by spiral gradient endpoint technique and assessment of effects of an efflux pump inhibitor on MICs of resistant strains

 

Author: Ip, Sze Yin Stella
Title: Determination of fluoroquinolone MICs by spiral gradient endpoint technique and assessment of effects of an efflux pump inhibitor on MICs of resistant strains
Degree: M.Sc.
Year: 2013
Subject: Quinoline.
Anti-infective agents.
Staphylococcus aureus.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: 67 leaves : ill. (some col.) ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2637219
URI: http://theses.lib.polyu.edu.hk/handle/200/7059
Abstract: Multidrug resistant (MDR) strains of Staphylococcus aureus cause serious problems worldwide. Methicillin-resistant S. aureus (MRSA) has been the most frequently reported MDR isolate for some years and more recently we have seen the development of MRSA which is also resistant to vancomycin known as Vancomycin intermediate resistant S. aureus (VISA). We need a rapid, inexpensive and reliable method for the detection of hVISA/VISA. Currently diagnostic routines in many laboratories focus on higher sensitivity and specificity but require 48 hours of incubation. However, all routine tests require overnight testing before results can be obtained. The E test is a simple rapid method for minimum inhibitory concentrations (MICs) determination of organism, but this method is quite expensive when several drugs are tested. SGE is highly sensitive and reproducible for MICs determinations by an agar gradient method. SGE techniques produce more powerful and precision results for antimicrobial compounds and their effects on organism growth. Fluoroquinolones are oral, broad-spectrum bactericidal agents widely used in both community and hospital settings. Fluoroquinolones interact with two essential bacterial enzymes, DNA gyrase and topoisomerase IV, for their bactericidal activity. The presence of multidrug resistant (MDR) efflux pumps lead to removal of a wide range of structurally compounds including antibiotics. The NorA protein of S. aureus is an active transporter and is responsible for the efflux of substances including ciprofloxacin. Antibacterial agents such as ciprofloxacin may be tested for their susceptibilities in multidrug resistant strains by SGE. Results of this study showed high level of resistance to ciprofloxacin and this resistance was due to mutations in gyrA and parC genes in addition to efflux mechanism. The MICs of ciprofloxacin against multidrug resistant isolates was reduced from >16 mg/L to 8mg/L when used in combination with 5'- methoxyhydnocarpin (5-MHC). This result indicates that 5-MHC is a potential efflux pump inhibitor for multidrug-resistant gram-positive organisms and warrants further investigation.

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