南臺灣困難梭狀芽孢桿菌之分子流行病學－回顧性研究

Molecular Epidemiology of Clostridium difficile in Southern Taiwan-A Retrospective Study

郭淑芳(Shu-Fang Kuo) ； 簡春治(Chun-Chih Chien) ； 劉仲康(Jong-Kang Liu) ； 尤慧玲(Huey-Ling You) ； 邢福柳(Hock-Liew Eng)

《Journal of Biomedical & Laboratory Sciences》 25卷2期 (2013/06) Pp. 63-69

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，本研究嘗試探討南台灣某醫學中心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，使用multiplex PCR來檢測tcdA、tcdB及cdtA、cdtB的基因，利用基因定序法來檢測tcdC基因的變異情況。藉以了解南台灣困難梭狀芽孢桿菌的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。

關鍵字

困難梭狀芽孢桿菌相關性腹瀉

並列摘要

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 has significantly increased for those over the age of 40, and the number increases from the age of 40 and peaked at the age of 80, and after that the number gradually decreases. In terms of the usage of antibiotics, other concomitant microbial infections, and death rate and fever, nosocomial-infection patients all have significantly higher rates than those of community-acquired. Furthermore, toxin genotype study indicated that there were equal amounts in toxigenic and non-toxigenic strains, that the proportion infected by toxigenic strains was higher in community-acquired patients than in nosocomial-infection patients, and that 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.

並列關鍵字

Clostridium difficile ； Clostridium difficile associated diarrhea ； multiplex PCR