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博碩士論文 etd-0016114-153427 詳細資訊
Title page for etd-0016114-153427
論文名稱
Title
南臺灣困難梭狀芽孢桿菌之分子流行病學
Molecular epidemiology of Clostridium difficile in southern Taiwan
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
81
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2013-12-11
繳交日期
Date of Submission
2014-01-16
關鍵字
Keywords
C. difficile infection、binary toxin、multiplex PCR、困難梭狀芽孢桿菌相關性腹瀉、Clostridium difficile
binary toxin, multiplex PCR, C.difficile infection, Clostridium difficile associated diarrhea, Clostridium difficile
統計
Statistics
本論文已被瀏覽 5735 次,被下載 625
The thesis/dissertation has been browsed 5735 times, has been downloaded 625 times.
中文摘要
困難梭狀芽孢桿菌相關性腹瀉(Clostridium difficile associated diarrhea ,CDAD)的發生率近年來不斷升高,2003~2005年CDAD在北美和歐洲出現了地區性的爆發流行,其流行株C. difficile NAP1/B1/027出現基因變異,產毒素的能力增強,患者的死亡率增高,已經成為一個嚴重的公共衛生問題,因此引起醫學界的重視。目前,困難梭狀芽孢桿菌已成為院內感染性腹瀉的主要病原菌。因此,本研究嘗試探討南臺灣某醫學中心2008年至2009年C. difficile菌株的流行病學分析。除了做病歷回溯以外,我們也以分子技術的方法,利用multiplex PCR來檢測tcdA、 tcdB 及cdtA、cdtB的基因和基因定序法來檢測tcdC基因的變異情況。藉以了解南臺灣困難梭狀芽孢桿菌的產毒型 (toxinotype)之流行率、分子類型、院內感染與社區感染CDI(C. difficile infection)病人之流行病學。本研究結果發現,40歲以上的CDI病患有明顯增加的趨勢,40歲開始增加一直到80歲達到巔峰,之後隨著年齡逐漸下降。院內感染CDI病人在抗生素使用、其他共存微生物感染、死亡率、發燒等都明顯高於社區感染。毒素基因型別的檢測結果:產毒素與不產毒素的菌株各半,而產毒素菌株在社區感染比例高於院內感染;毒素型別則以產生binary toxin者最少,且以社區感染的比例較高。其中32株會產生binary toxin的菌株,全部都有tcdC基因的變異,包括鹼基對的缺失、插入或突變,導致終止密碼提前產生。本文藉由毒素型別檢測與病歷回溯進行研究分析,期望能藉由本研究結果提供院內感染防治之參考。
Abstract
The incidence of Clostridium difficile associated diarrhea (CDAD) has been rising in recent years. There were CDAD regional outbreaks in North America and Europe during the years from 2003 to 2005. Genetic variations have been identified world-widely. They are closely related to high toxigenic strains and clinical pathogenesis. The epidemic strains of CDAD (C. difficile NAP1/B1/ 027), with its high toxigenic ability, results in an increasing mortality rate and has become a serious public health problem and draws great attention to medical profession. At present, C. difficile has become the main pathogens of nosocomial diarrhea. In this study, we attempted to characterize the epidemiological analysis of C. difficile strains during the years of 2008-2009 in a medical center of southern Taiwan, especially emphasized on the difference between nosocomial and community-acquired CDI. The multiplex PCR was used to detect the tcdA、tcdB and cdtA、cdtB, and deployed a gene sequencing method to detect tcdC mutation. We found that the number of CDI patients significantly increased for those over the age of 40, and the incidence increased from the age of 40 and peaked at the age of 80, and after that the number was gradually decreased. In terms of the usage of antibiotics, other concomitant microbial infections, death and fever, nosocomial-infected patients were all significantly higher than those of community-acquired. Furthermore, toxin genotype study indicated that there were equal amounts in toxigenic and non-toxigenic strains, however, the proportion infected by toxigenic strains was higher in community-acquired patients than in nosocomial-infection patients, and a higher proportion in community-acquired CDI patients were infected by binary toxin. All 32 strains that produced binary toxin had tcdC gene variations, including base pair deletion, insertion and mutation, and were in advance to produce the stop codon. Hopefully, the results of this molecular epidemiological study would be helpful for future prevention and control of the CDAD.
目次 Table of Contents
論文審定書 i
誌謝 ii
中文摘要 iii
ABSTRACT iv
目錄 vi
表目錄 viii
圖目錄 ix
縮寫表 x
第一章 簡介 1
壹、 困難梭狀芽孢桿菌的發現與特性 1
貳、 流行病學 2
參、 毒素因子 3
肆、 臨床表現(Clinical manifestations) 5
伍、 危險因子 6
陸、 治療與抗藥性現況 7
柒、 困難梭狀芽孢桿菌感染的檢測 9
捌、 培養特性 12
第二章 研究動機與實驗設計 13
第三章 材料、方法與研究對象 14
材料 14
方法 15
一.Strains and DNA preparation 15
二.tcdA、tcdB、cdtA and cdtB analysis 17
三.tcdc gene analysis 17
四.產毒性試驗 19
五.研究對象病歷回溯 19
第四章 結果 21
第五章 討論 24
結論與建議 27
參考文獻 29
表 38
圖 50
附件一論文投稿 63
附件二得獎獎狀 70
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