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臨床重要細菌的抗藥性及流行病學研究

Study on antibiotic resistance and epidemiology of clinically important bacteria

臨床重要細菌的抗藥性及流行病學研究



蕭樑基
Leung-Kei Siu

研究員 Investigator
Phone: (037) 246-166 ext. 35506
Fax: (037) 586-457 
E-mail: lksiu@nhri.org.tw

 

 

I have been a clinical microbiologist since the graduation from Ph.D. program in the department of Clinical Microbiology, University of Hong Kong and became a postdoctoral fellow thereafter. During the postdoctoral fellowship, he was mainly working on the Helicobacter pylori study as well as antibiotic resistant mechanism. He joined the division of Clinical Research, National Health Research Institutes (NHRI) in 1998 and major in antibiotic resistance and specific infectious diseases in Taiwan.

 

Research Interests

Therapeutic control of antibiotic resistance bacteria has been a major clinical problem for the past 40 years.  Bacteria are most often resistant to antibiotics as a result of acquisition of resistant gene or gene mutation.  Studies showed that newly developed antibiotics will shortly fail to be active against the bacteria because of the emergence of resistance.  Some resistant bacteria have been found to exist even before the antibiotic was developed.  The inappropriate use of new extended spectrum antibiotics complicated the problem even more.  Since resistance is a largely unavoidable consequence of widespread utilization, it would seem prudent to ensure that the use of drugs is selective by exercising prudent judgment and not excessive.  Conspicuously, the actual prevalence of resistance should be monitored continuously year by year.  Direct extrapolation of study results from other geographic areas should be avoided since the local prevalence of resistance is unlikely to be identical to that reported elsewhere.  If such information is available, it can help to design strategies for maximizing the therapeutic usefulness of drugs and minimizing the emergence of resistance. Although we have yet to reach such a worst-case scenario in antibiotics resistance, we cannot just simply ignore the problem or wait until it is uncontrollable.  If we ignore, single drug therapy will simply become obsolete.

 

 

Control of multiple resistant bacteria has been a major clinical problem for the past 40 years. Bacteria are often extended their resistance to antibiotics as a result of the acquisition of resistant genes or through the mutation of target gene binding. Our results showed that newly developed antibiotics are shortly failed to be active against the bacteria because of the emergence of resistance. Some resistant bacteria have been found to exit even before the antibiotic was used in our locality. In our bβ-lactam resistance study, different bβ-lactamases including some novel bβ-lactamases described above in our finished projects differ in their substrate or inhibition profiles through specific point of gene mutation. The inappropriate use of new developed cephalosporins complicated the problem even more. The finished projects described above highlighted the importance of antibiotic usage for the severe illnesses as well as the importance of control resistance spreading. Once a new resistance mechanism is discovered, it becomes possible to predict the likelihood and probable targets of spread, and the potential for further mutations. In the studies described above which included ongoing projects, sequencing data revealed that a single base of nucleotide change is already sufficient for novel resistance to emerge. Thus once a spontaneous mutation appears in resistant gene mediating a particular type of resistance, subsequent use of the same antibiotic would exert a selective pressure for those bacteria with the advantage of resistance. Eventually, an explosive increase in the population of the resistant phenotype will occur. Our results showed that direct extrapolation of the experience or the guidelines from other geographic regions should be avoided, since the local prevalence of resistance is unlikely to be identical to that reported elsewhere. The use of antibiotics should be evaluated periodically to avoid the selective pressure. Furthermore, accurate detection of resistance will enable our exercising prudent judgment and will discourage excessive use of antibiotics. Briefly combine all the information that I have described above, my collaborators and I have refined the routine susceptibility testing method, with regard to their performance and result interpretation, taking into account of the prudent use of antibiotics, the evolution of antibiotic resistance. Finally, in depth study on the mechanisms of resistance has lead to the rational design of new drugs and avoidance of the inappropriate use of drugs resulting in the emergence of novel resistant mechanism. In summary, the more we understand, the easier it is to control. It is anticipated that the future work will be difficult but rewarding.

 

Selected Publications

1.      Kuo-Ming Yeh, Jung-Chung Lin, Fon-Yi Yin, Chang-Phone Fung, Han-Chang Hung, Leung-Kei Siu, and Feng-Yee Chang. Revisit of an Important Virulence Determinant, magA, and Its Surrounding Genes for Pyrogenic Liver Abscess: the Exact Role in Klebsiella pneumoniae Serotype K1 Capsule Formation. J Infect Dis. 2009. (Accepted) *Corresponding author

 

2.      Ma L, Lin CJ, Chen JH, Fung CP, Chang FY, Lai YK, Lin JC, Siu LK*; the participating hospitals of Taiwan Surveillance of Antimicrobial Resistance (TSAR). Widespread Dissemination of Aminoglycoside Resistance armA or rmtB Genes in CTX-M Type Extended Spectrum {beta}-lactamase-Producing Klebsiella pneumoniae in Taiwan. Antimicrob Agents Chemother. 2009. 53:104-11. *Corresponding author

3.      Lu PL, Tsai JC, Chiu YW, Chang FY, Chen YW, Hsiao CF, Siu LK. Methicillin-Resistant Staphylococcus Aureus Carriage, Infection and Transmission in Dialysis Patients, Healthcare Workers and their Family Members. 2008. Nephrol Dial Transplant. 23(5):1659-65. * Corresponding author

4.      Fung-CP and L. K. Siu*. Virulence of Klebsiella pneumoniae serotype K2 should not be underestimated in K. pneumoniae liver abscess. Clin Infect Dis. 2007. 45(11):1530-1. *Corresponding author

 

5.      Kuo-Ming Yeh, Feng-Yee Chang, Chang-Phone Fung, Jung-Chung Lin, L. K. Siu*. 2006. Serotype K1 capsule rather than magA per se is really the virulence factor in Klebsiella pneumoniae strains causing primary pyogenic liver abscess. J Infect Dis. 194(3):403-4. *Corresponding author

 

6.      Jung-Chung Lin, L. K. Siu, Chang-Phone Fung, Hsiao-Hui Tsou, Jaang-Jiun Wang, Chiung-Tong Chen, Shu-Chuan Wang, and Feng-Yee Chang*. 2006. Impaired Phagocytosis of Capsular Serotypes K1 or K2 Klebsiella pneumoniae in Type 2 Diabetes Mellitus patients with Poor-Glycemic Control. J Clin Endocr Metab. 91(8):3084-7. Contributed equally.

 

7.      Ling Ma, Jimena Alba, Feng-Yee Chang, Masaji Ishiguro, Keizo Yamaguchi, L. K. Siu*, and Yoshikazu Ishii. 2005. A Novel SHV-Derived Extended-Spectrum b-Lactamase (SHV-57) That Confers Resistance to Ceftazidime But Not Cefazolin. Antimicrob. Agents Chemother. 49(2):600-5.   *Corresponding author

 

 

 

 


 

 


 

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