| Summary: | 碩士 === 臺北醫學大學 === 醫學研究所 === 94 === Infections caused by multidrug-resistant bacteria expressing extended -spectrum -lactamases (ESBLs) pose serious challenges to clinicians. Extended-spectrum -lactamases (ESBLs) are plasmid-mediated bacterial enzymes that confer resistance to a broad range of -lactams. Most ESBLs have evolved by genetic mutation from native -lactamases, such as TEM-1, TEM-2, and SHV-1. These parent enzymes are commonly found in Gram-negative bacteria, particularly enterobacteriaceae; they are highly active against penicillins and modestly active against early-generation cephalosporins.
The prevalence of infections caused by extended-spectrum -lactamase (ESBL)–producing Enterobacteriaceae is increasing worldwide. Because ESBL-producing strains are resistant to a wide variety of commonly used antimicrobials, their proliferation poses a serious global health concern that has complicated treatment strategies for a growing number of hospitalized patients. Although ESBLs have been reported most frequently in Escherichia coli and Klebsiella species , they have been found in other bacterial species as well, including Salmonella enterica, Pseudomonas aeruginosa, and Serratia marcescens .
Bacterial resistance to an increasing number of antimicrobial agents is a well-established problem. In recent years, a novel group of DNA elements able to incorporate antibiotic resistance genes by a site-specific recombination have been identified in Gram-negative bacteria. These elements have been termed integrons. Gene transfer into small genomes and into plasmids is via site-specific recombination. Integron act as reporters of antibiotic resistance cassettes. As such, integron-driven gene capture is likely to be an important factor in the more general process of horizontal gene transfer in the evolution of bacterial genomes.
An increase in the number of cases of ESBL has been observed over the past few years in the hospital of major medical center in Taiwan, and will be the great challenge to overcome this threatens. There are total 323 drug-resistant ESBL have collected, in which 223 clinical isolates are from the Taipei Medical University Hospital. Other 100 samples were kindly provided by Dr. P. R. Hsueh (NTU, School of Medicine) which collected from the major medical centers in Taiwan including north, central, south, and east regions. The objectives of this proposed project are (i) to investigate the molecular epidemiology of ESBL colonization and infection in the hospital, (ii) to evaluate the diffusion of integron types among clinical isolates of ESBL in Taiwan and to carry out a molecular characterization of their gene cassette arrays, (iii) to study the molecular epidemiology of ESBL antimicrobial resistance, (iv) to evaluate the contribution of integrons and efflux pump to the multiple antibiotic resistance and nosocomial spread of ESBL strains, and (v) to identify clinical and therapeutic factors contributing to the selection of multidrug-resistant ESBL in the hospital environment.
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