背景
超廣效性乙醯胺酶Extended-spectrum ß-lactamases (ESBLs)是在1983年首次被報告。大部分的ESBLs抗藥基因可以歸類為3大類: TEM， SHV與 CTX-M。在台灣，由於乙醯胺 (β- lactam)與廣效性頭孢菌素(cephalosporins)過度使用，所以使得具有ESBLs的病原菌在醫院內之感染症急劇增加，但其在社區感染之流行病學則未知。
研究目的
台灣關於ESBLs感染症的文獻，多數仍以院內感染為主，少數社區感染的文獻收案標準是以住院時間來做區隔，然而這樣的方式可能會將部分醫療照護相關造成的感染症納入社區感染中，所以此次研究將醫療照護相關之感染從社區感染區隔出來，進而評估社區感染之分子流行病學及病患特性。
研究方法
以病例回溯方式進行，自97年11月到98年2月間，在高雄醫學大學附設醫院與小港醫院病患中，以double disc法或Vitek2 (bioMérieux) system確認具ESBLs表現型Escherichia coli 或 Klebsiella spp.感染者進行收案，只收入期間病患第一次發生的感染症，排除菌株死亡、鑑定錯誤、病歷記載不完整、菌株移生者。
結果
研究期間，共分離出1846株 Escherichia coli 、779株Klebsiella spp.，依院內感染定義區分出院內感染(hospital-acquired, HA) ，而住院不滿48小時且採檢前1個月無住院記錄、3個月內無任何醫療照護相關危險因子者視為社區感染(community-acquired, CA) ，其餘則歸入醫療照護相關感染(healthcare-associated, HCA)。ESBLs E. coli在社區盛行率為3.4% (34/1008)，K. pneumoniae則為2.8% (9/324)。所有183株具ESBLs之E. coli與Klebsiella spp 以HA佔最多數為43.1%，檢體大多為尿液，共100件(54.6%)。目前社區感染對amikacin仍未出現抗藥性菌株，且對piperacillin/tazobactam尚有85.3%以上的感受性，可為治療社區感染另一選擇。以多變項分析可發現這三組ESBLs之病人特徵差異如下，醫療照護相關感染的平均年齡最大,與另兩組有顯著差異，全部院內感染皆在培養前3個月曾使用抗生素，尤其是cephalosporin也有顯著差異，社區感染有81.4%為尿液檢體，明顯高於其他組別。在院內感染具ESBLs菌株之抗藥基因以SHV (73.4%)比例最高，醫療照護相關感染裡則可以發現TEM成了最主要的抗藥性基因，然而在社區感染CTX-M盛行率高達59.0%，尤其CTX-M9 group (46.5%)，比起院內感染10.1%有顯著差異(P<0.0001)。此次在社區感染中並未分離出K. oxytoca，PFGE結果
似度高的cluster裡，沒有發現社區型的ESBLs，顯示在社區感染的ESBLs 並沒有epidemic strains，這次研究發現具SHV-31之K. pneumoniae 8株(HA：3株、HCA：5株)，還有一株醫療照護相關感染K. pneumoniae 具CTX-M55與SHV-12。

結論
在台灣，具ESBLs表現型E.coli 或 Klebsiella spp確實存在於真正的社區感染，且此次研究發現目前台灣尚未有文獻報告過SHV-31與CTX-M55。

Background
Extended-spectrum ß-lactamases (ESBLs) was reported for the first time in 1983. The most prevalent types of ESBLs are TEM, SHV and CTX-M. In recent years,Extended-spectrum ß-lactam producing bacteria has became prevalent in hospital-acquired infection. There is limited clinical information about ESBLs producing isolates as a cause of community-acquired infection.

Objective
Most literatures about ESBLs were hospital-acquired infection in Taiwan. Some studies used the duration of hospitalization before bacteria isolation date as criteria of community-acquired infection. However,such cases could be healthcare -association infection as community-acquired infections. This study used updated criteria to differentiate community acquired, healthcare–associated, and hospital-acquired infections. We investigated the molecular epidemiology and clinical characteristics of community-acquired ESBLs infections.

Method
All non-duplicate isolates was screened by double disc diffusion and Vitek2 between November 2008 to February 2009 at two hospitals (kaohsiung medical university hospital and hsiao-kang hospital). Only the first occurred in patients with infectious diseases by Escherichia coli or Klebsiella spp. were collected in retrospective review of medical records. We excluded the patients who were colonizationed or with incomplete medical records.

Result
1846 Escherichia coli and 779 Klebsiella spp. were deteced at the study period. We defined hospital-acquired infections (HA) as the nosocomial infection guildline from CDC.Community-acquired infection(CA) was defined by a positive culture obtained at the time of hospital admission or within the 48 hours after hospital admission for patients who did not hospitalized in the 30 days before and without any criteria of healthcare–associated. Healthcare–associated infection (HCA) was defined by those persons have been receiving health care in an outpatient facility or received invasive therapy. The prevalence of ESBLs
E. coli in the community-acquired infection was 3.4% (34/1008), K. pneumoniae was 2.8% (9/324).183 ESBLs Escherichia coli or Klebsiella spp. isolates were collected. Of these cultures, 43.1% were hospital-
acquired infection. Total of 100 (54.6%) urine samples were the most prevalent.Community-acquired infection without resistant strains of amikacin, and have 85.3% susceptible rate of piperacillin / tazobactam.
The results by multivariate logistic regression show significant in age, previous cephalosporin used and urine samples.Healthcare-associated infection were eldest compared with other groups. All hospital-acquired infection were previous cephalosporin used. The propotion of urine samples in community-acquired infection were higher than the other groups . SHV (73.4%) was the most prevalent of hospital-acquired infection. TEM was the major resistance gene in healthcare-associated infection, but the most frequent in community-acquired infections was CTX-M (59.0%), CTX-M9 (46.5%) group was especially. The propotion of CTX-M was higher in the group with community-acquired infection than in the hospital-acquired infection. group (59.0% versus 10.1%; P&lt;0.0001). K oxytoca was not been isolated in this study. There were no clusterings in PFGE dendrography of community -acquired infection that seems without epidemic strains. Eight isolates (HA:3, CA:5)of K. pneumoniae were found contain SHV-31, and 1 K. pneumoniae of healthcare-associated infection produced CTX-M55 and SHV-12.

Conclusion
In Taiwan, ESBLs E.coli or Klebsiella spp does exist in community
-acquired infection. Eight isolates produced SHV-31 and 1 of CTX-M55 that have not been reported in Taiwan.

論文通過合格證明………………………………………………….1a
中文摘要………………………………………………………….…2a
Abstrate………………………………………………………….…..5a
致謝………………………………………………………………….7a
目錄…………………………………………………………….……9a
表目錄………………………………………………………….……12a
圖目錄……………………………………………………….………14a
縮寫與全名對照表…………………………………………….……15a
台灣社區感染ESBLs Escherichia coli與Klebsiella spp.
之分子流行病學
第一章 研究背景……………………………………………….……..1
第二章 文獻回顧……………………………………………………...3
第一節 抗生素簡介………………………………...…….………3
第二節 腸道桿菌科細菌………………………………………....3
2.1 大腸桿菌…………………………………………………4
2.2 克雷白氏肺炎桿菌………………………………………5
第三節 細菌抗藥性機轉…………………………………………6
第四節 ESBLs ……………………………………………………7
4.1 分類………………………………………………………7
4.2 抗藥性表現型與檢測方法……………………………..11
第五節 脈衝式膠質電泳分析…………………………………..14
第三章 研究目的……………………………………………………16
第四章 研究方法 …………………………………………………..17
第一節 研究設計……………………………………………….17
1.1 研究類型………………………………………………..17.
1.2 研究時間、地點、對象………………………………..17
第二節 研究方法………………………………………………..17
2.1 檢體準備………………………………………………..17
2.2 測定項目與方法 ………………………………………18
2.3 病例回溯………………………………………………...21
第三節 各變項之定義…………………………………………...22
第四節 統計方法………………………………………………...23
第五章 研究結果……………………………………………………..25
第一節 病患之基本資料………………………………………...25
第二節 藥物感受性試驗結果……………………………………27
第三節 分組比較結果……………………………………………29
第四節 PFGE結果……………………………………………….34
第六章 討論…………………………………………………………..36
第一節 與其他文獻比較3………………………………………36
第二節 PFGE結果……………………………………………….42
第三節 研究限制…………………………………..……………..43
第四節 總結………………..……………………………………..43
附錄…………………………………..………………………………...73
參考文獻………………………………..……………………………...74

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