Author: Zhang, Ming
Title: Epidemiology and molecular characteristics of staphylococcus aureus and coagulase-negative staphylococci with reduced antiseptic susceptibility in Hong Kong
Degree: Ph.D.
Year: 2013
Subject: Drug resistance in microorganisms -- Genetic aspects.
Staphylococcal infections.
Hong Kong Polytechnic University -- Dissertations
Department: Department of Health Technology and Informatics
Pages: xl, 395 p. : col. ill. ; 30 cm.
Language: English
Abstract: Over the past decade, there has been increasing efforts aimed at the prevention of hospital infections caused by methicillin-resistant Staphylococcus aureus (MRSA). One of the main preventive measures has been the use of antiseptic agents for decontamination of surfaces and hand hygiene. Guidelines recommend using antiseptics for decolonization of high risk groups and routine cleansing of all patients when basic interventions have failed to reduce rates of MRSA infection to acceptable levels. Frequently touched surfaces should also be decontaminated with disinfectant. However, recently there has been increasing concern that increased use of biocides may contribute to the emergence and/or selection of resistant pathogens. Staphylococcal strains harboring genes coding for increased resistance to quaternary ammonium compounds (QACs) and other disinfectants (qac genes) as demonstrated by increased minimum bactericidal concentrations (MBCs) to antiseptics as described in several studies and there is evidence that carriage of these genes may be increasing. Widespread use of biocides may impose selective pressure and contribute to the emergence of bacteria with decreased antiseptic susceptibility. In addition, there is evidence that use of biocides may contribute to the emergence of cross-resistance and co-resistance between widely used biocides and antibiotics. However, the distribution of qac genes in S. aureus and CNS has only been investigated in clinical isolates, with most focus on MRSA, and little is known about the frequency of qac genes in colonizing strains in the population and the environment. There is a need for more studies to determine colonization and contamination rates with strains harbouring qac genes in various populations and locations as well as for evidence for the development of cross-resistance to methicillin and non-beta-lactam antibiotics. Residues of biocides increase bacterial exposure, which may lead to selection of mutant strains possessing broad spectrum efflux pumps displaying reduced susceptibility to both biocides and antibiotics. Determination of reduced susceptibility to biocides is somewhat difficult as a convenient gradient method for MIC determination had not been developed for antiseptics. Spiral gradient endpoint (SGE) technique, is a gradient method for MIC determination which is simple, rapid and cost-effective and has been shown to be suitable to determine antibiotic MICs for fastidious organisms and for determination of vancomycin resistance. SGE has the advantages of employing a concentration gradient and is suitable for a wide range of substances and overcomes the problem of large increments experienced in conventional dilution methods. The purpose of this research was to provide significant and original contributions to the knowledge base of antiseptic resistance genotypes in S. aureus and coagulase-negative staphylococci in selected populations and environments in Hong Kong. The need for an accurate and simple method for determination of antiseptic MICs was addressed by development and evaluation of SGE for these agents. Finally, it aimed to determine the effects of increased and prolonged exposure to disinfectants on levels of antiseptic resistance. Overall, this provided a framework for effective detection of reduced antiseptic susceptibility, guidance for antimicrobial selection in treatment of S. aureus and MRSA carrying antiseptic resistant genes, improving infection control, and contributing to better clinical outcomes.
This is the first study of qac gene prevalence in staphylococci in Hong Kong. It examined a wide variety isolates including colonizing strains from nurses, the general population, and the elderly residents in both nursing homes and the community as well as clinical isolates and those contaminating the public environment and hospital surfaces. The study aimed to determine if the health care environment increased risk of strains carrying antiseptic resistance genes. The increased proportion of antiseptic resistance gene positivity in mecA positive isolates suggests co-selection of these genes, contributing to survival of MRSA in community and health care facilities including hospital and nursing homes. Use of antiseptics may be selecting for antibiotic-resistant strains and assisting their survival in the environment. In order to carry out further studies on increasing biocide resistance, a simple, flexible test for determining the MIC of a biocide or biocide mix is needed. This study evaluated SGE for determination of MICs of antiseptics and showed that SGE offers a precise and accurate method for biocide MIC measurement. The induction study demonstrated that biocide exposure could indeed select for strains with increased tolerance at sub-MIC concentrations, being disinfectant reduced susceptibility isolates. In conclusion, this study has demonstrated the wide dissemination of strains carrying antiseptic resistance genes in both the community and healthcare facilities in Hong Kong. Rates of carriage of these genes were higher in healthcare settings possibly reflecting increased disinfectant exposure. There is a need for further investigation of the importance of reduced antiseptic susceptibility and its relevance in infection control.
Rights: All rights reserved
Access: open access

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