以製造CTX-M型超廣譜乙醯胺酶之克雷白氏肺炎桿菌探討氨基苷類及喹諾酮類抗藥性在台灣的廣泛傳播

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研究生：	林琦然 Lin, Chi-Jan
論文名稱：	以製造CTX-M型超廣譜乙醯胺酶之克雷白氏肺炎桿菌探討氨基苷類及喹諾酮類抗藥性在台灣的廣泛傳播 Widespread dissemination of aminoglycoside and quinolone resistance in CTX-M type Extended spectrum β-lactamases-producing Klebsiella pneumoniae in Taiwan
指導教授：	黎耀基 Lai, Yiu-Kay 蕭樑基 Siu, Leung-Kei
口試委員:
學位類別：	碩士 Master
系所名稱：	生命科學暨醫學院 - 生物科技研究所 Biotechnology
論文出版年：	2009
畢業學年度：	97
語文別：	英文
論文頁數：	62
中文關鍵詞：	克雷白氏肺炎桿菌
外文關鍵詞：	Klebsiella pneumoniae, CTX-M, quinolone, aminoglycoside
相關次數：	點閱：2 下載：0
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在台灣第三期全國微生物抗藥性監測計劃 (TSAR)收集到的235株產生超廣譜乙醯胺酶的克雷白氏肺炎桿菌 (ESBL-KP)之中，104株 (43.4%) 及有124株 (52.8%)的菌株分別對amikacin及ciprofloxacin兩種抗生素具抗藥性。聚合酶鏈反應 (PCR)結果顯示出在amikacin抗藥菌株中有92株 (90.2%) 單獨具有CTX-M型乙醯胺酶或者是具有CTX-M型乙醯胺酶伴隨著SHV型或CMY-2之乙醯胺酶，而ciprofloxacin抗藥菌株都攜帶著CTX-M型及SHV型的乙醯胺酶。而且CTX-M基因可藉由接合作用傳播。在amikacin或ciprofloxacin抗藥菌株中所發現的CTX-M型式分別為CTX-M-3，CTX-M-14及CTX-M-15而SHV型式主要為SHV-5，SHV-12及非超廣譜乙醯胺酶SHV-1及11型。在具有armA或rmtB基因之抗amikacin ESBL-KP及帶有質體傳播喹諾酮 (plasmid mediated quinolone resistance)基因之抗ciprofloxacin ESBL-KP的CTX-M基因的上游都可以發現轉位子 (IS element) ISEcp1 的插入。

在amikacin抗藥株中，CTX-M-1群普遍存在於armA 攜帶菌株中，相反的是在rmtB 攜帶菌株中主要為CTX-M-9群。在帶有質體傳播喹諾酮基因之ciprofloxacin抗藥株中，CTX-M-1群為最主要。分析合轉型子 (transconjugant)發現qnrB 基因與CTX-M-15或SHV-12共存。利用脈衝場凝膠電泳(pulsed field gel electrophoresis) 進行流行病學親緣分析發現amikacin抗藥株在流行病學上沒有親緣關係，代表抗藥性的獲得不是從少數抗藥菌株散佈。在ciprofloxacin抗藥株偵測到部份有流行病學上親緣關係，少數抗藥菌株散佈在三個醫院裡有被發現。

本研究結果顯示在amikacin抗藥株ESBL-KP中armA 或 rmtB 跟blaCTX-M 基因有相關性，同時在ciprofloxacin抗藥株ESBL-KP中質體傳播喹諾酮抗藥性基因與blaCTX-M 或blaSHV 的關聯也被發現。進一步的說，16S rRNA甲基酶與質體傳播喹諾酮抗藥性基因都跟blaCTX-M 或blaSHV在同一個質體上，並且可轉移。在CTX-M型的ESBL-KP中，氨基苷類抗藥性基因的傳播是藉由質體，而少數抗藥菌株散佈及質體傳播在喹諾酮類抗藥性基因之傳播有相同貢獻度，而在台灣已經是傳播廣泛。

Table of Contents
中文摘要    i
English abstract    iii
Acknowledgement    v
Table of content    vi

Widespread dissemination of aminoglycoside and quinolone resistance in CTX-M type Extended spectrum □-lactamases-producing Klebsiella pneumoniae in Taiwan
1. Introduction    1
1-1□General introduction    1
1-2□□-lactam antibiotics and resistance mechanism    2
1-3 Old extended spectrum □-lactamases (ESBLs)    2
1-4 New ESBLs and treatments    4
1-5 Resistance mechanism of aminoglycoside    5
1-6 Resistance mechanism of quinolone    7
1-7 Epidemiology of CTX-M type ESBLs    8
1-8 Aim of study    8
2. Methods and Materials    10
2-1 Bacterial strains    10
2-2 Susceptibility testing and confirmation of ESBL producer    10
2-3 Polymerase Chain Reaction amplification and sequencing    11
2-4 Conjugation experiments    12
2-5 PFGE analysis    12
2-6 Plasmid restriction enzyme digestion profile    13
2-7 Southern blot hybridization by armA, rmtB and blaCTX-M probe    14
3. Results    15
3-1 Susceptibility testing results    15
Study of amikacin resistant mechanism
3-2 Detection of 16S rRNA methylase, □-lactamase, class 1 integron, ISEcp1 and IS26    15
3-3 PFGE analysis    17
3-4 Conjugation and plasmid restriction enzyme-digested profile    18
3-5 Southern blot hybridization with blaCTX-M, armA and rmtB probes    19
Study of ciprofloxacin resistant mechanism
3-6 Detection of gyrA, parC, qnrA, qnrB, qnrS, aac(6’)Ib-cr, ISEcp1 and □-lactamases’s genes    20
3-7 PFGE analysis    23
3-8 Conjugation and susceptibility test    23
5. Discussion    26
4-1 Study of amikacin resistant mechanism    26
4-2 Study of ciprofloxacin resistant mechanism    30
6. Tables    35
7.    Figures    43
Reference    49
Appendixes    56

                                

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