南台灣ceftriaxone抗藥性非傷寒沙門氏菌之抗藥性機轉與分子流行病學分析

Molecular epidemiology and resistance mechanisms of ceftriaxone-resistant non-typhoidal Salmonella in southern Taiwan

謝品萱(Ping-Hsuan Hsieh)

指導教授 ： 張仲羽

共同指導教授 ： 盧柏樑(Po-Liang Lu)

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2017年)

摘要

非傷寒沙門氏菌能在動物以及人類造成感染，是常見的人畜共通傳染病原菌，具ceftriaxone抗藥性非傷寒沙門氏菌逐漸增加的趨勢已引起全球高度關注，但在南台灣卻缺乏相關的流行病學研究。高雄市立小港醫院於2004-2015 年從臨床病人檢體共分離 651 株非傷寒沙門氏菌，ceftriaxone抗藥性非傷寒沙門氏菌佔 2.5％，本研究主要針對其中12株ceftriaxone 抗藥性非傷寒沙門氏菌進行分子流行病學分析，包含鑑定菌株血清型，偵測各類型 β-lactamase 基因，並以PCR based replicon typing 進行質體分型，利用PFGE分型探討菌株親緣關係。12 株對ceftriaxone 產生抗藥性的非傷寒沙門氏菌，有11株(91.7%)屬於 O 抗原 B 群，血清型都是Salmonella enterica subsp.enterica serovar Typhimurium (S.Typhimurium)，僅有1株屬於O抗原C群，血清型為S.Thompson。11株S.Typhimurium 至少帶有一種β-lactamase基因，類型包括 TEM-1、CMY-2 及 CTX-M-14，其中以CMY-2 最多(8株)。有9株(75%)可以PCR法得到質體互不相容群分型，其中8株帶有IncI1或IncHI2質體 (IncI13株，IncHI2 2株，3株同時具IncHI2 和 IncI1 之特性)，1株為IncFIB。PFGE分型結果可以分為3個 pulsotype (pulsotypes I, II, III)，11 株S. Typhimurium 分別屬於 Pulsotypes I 和 II (Pulsotype I 6 株，pulsotype II 5 株)。本研究結果顯示，南台灣非傷寒沙門氏菌 ceftriaxone 抗藥性主要與 CMY-2有關，有兩個 S. Typhimurium clone 負責 ceftriaxone 抗藥性散佈，IncI1或 IncHI2 質體也可能參與抗藥性的散播。

關鍵字

非傷寒沙門氏菌 ； ceftriaxone抗藥性 ； 分子流行病學

並列摘要

Non-typhoidal Salmonella (NTS) represents an important human and animal pathogen worldwide. Increasing ceftriaxone resistance in non-typhoidal Salmonella species has been a serious problem for public health, however, data on this issue is lacked in southern Taiwan, the main livestock source in Taiwan. Six hundred and fifty-one NTS isolates were collected in Kaohsiung Municipal Hsiao-Kang Hospital from 2004 to 2015. Twelve ceftriaxone resistant NTS isolates were further characterized for serotypes, β-lactamase genes, PCR-based replicon typing (PBRT) of plasmids and clonal relatedness by PFGE in this study. Eleven (91.7%) of the 12 ceftriaxone resistant NTS isolates belonged to serogroup B and Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) serotype. Only one isolate belonged to serogroup C and S. Thompson serotype. All the 11 S. Typhimurium isolates carried at least one β-lactamase gene, the majority of which were CMY-2 (8/11). Plasmid replicon types were identified in 9 (75%) isolates. Among them, three were IncI1, two were IncHI2, one was IncFIB and three had both replicons of IncI1 and IncHI2. The PFGE analysis revealed that 11 S. Typhimurium isolates belonging to 2 pulsotypes (pulsotypes I and II comprised 6 and 5 isolates, respectively) indicated clonal relatedness. In conclusion, CMY-2 was the predominant β-lactamase gene associated with ceftriaxone resistant NTS. The clonal spread of two S. Typhimurium clones results in increased ceftriaxone resistance in southern Taiwan. IncI1 and/or IncHI2 plasmids may also contribute to the spread of ceftriaxone resistance in NTS.

並列關鍵字

Non-typhoidal Salmonella ； ceftriaxone resistance ； molecular epidemiology

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