2012-01-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657102摘要：腸內菌屬是臨床上重要的致病菌，carbapenems 類的抗生素為對抗其感染十分重要的治療用藥。許多研究發現近年來腸內菌屬的細菌對 carbapenem 抗生素的 抗藥性，有逐漸增加的現象。腸內菌屬細菌 carbapenem 抗藥性機轉主要包括分泌 ESBL 加上 outer membrane 的改變或 efflux pump 的大量表現，分泌 AmpC-lactamase 加上 outer membrane 的改變或 efflux pump 的大量表現，以及分泌 carbapenemase。其中以 carbapenemase 分泌的機轉，最引人重視。這些 carbapenemases 中，又以 Klebsiella pneumoniae carbapenemase (KPC type)和New-Delhi metallo-β-lactamase1 (NDM-1) enzymes，最令人矚目；主要原因為登錄 此兩種 carbapenemases 的遺傳物質，位於質體（plasmid）上，具有可在不同細菌 間轉移的特性。再加上 Carbapenem 抗藥性腸內菌（CRE）通常幾乎對所有的抗生 素均具抗藥性，其崛起著實是醫界的一大隱憂。我們的整合型計畫，針對台灣地區 CRE 菌株的流行病學而設計。在子計畫 一中，我們將探討發生 CRE 感染或移生的危險因子，描述 CRE 感染的臨床表現， 並找出是否有特殊的抗生素感受性模式，能幫助臨床醫師提早判定某一 CRE 菌株 是否為 carbapenemase producing。在子計畫二中，我們著重於分析 CRE 的 carbapenem 抗藥性是否導因於 carbapenemases 分泌，分析登錄 carbapenemase 基因 所位在的質體，其基因序列與分型為何，偵測 CRE 菌株是否會分泌 ESBL 或 AmpC-lactamase，測定 carbapenemase-producing CRE 的 fluoroquinolone 抗藥機轉（若為 抗藥性）。在子計畫三中，我們則著重於分析 CRE 菌株是否有 outer membrane porin 的改變與 efflux pump 的大量表現。<br> Abstract: Carbapenems are important antibiotics against bacteria belonging toEnterobacteriaceae. Recent studies demonstrates that carbapenem resistance among Enterobacteriaceae increases gradually. The mechanisms of carbapenem resistance among Enterobacteriaceae include production of extended-spectrum -lactamase (ESBL) plus outer membrane change or up-regulation of efflux pump, production of AmpC -lactamase plus outer membrane change or up-regulation of efflux pump, and production of carbapenemases. Among them, the most important one is production of carbapenemases because of the transferrability of their genetic materials. Of the carbapenemases found in Enterobacteriaceae, Klebsiella pneumoniae carbapenemase (KPC) and New-Delhi metallo--lactamase 1 (NDM-1) are of most interest because of their ability to be transferred between different bacteria. The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is worrisome, because these isolates usually also resist to other antibiotics in addition to carbapenems.Out integrated project is design to investigate the epidemiology of CRE in Taiwan. In subproject one, we will focus on the risk factor to acquire CRE infection/colonization, to investigate the clinical presentation, including outcome analysis, of CRE infection, and try to identify a surrogate marker for carbapenamse production by analyzing the drug susceptibility patterns. In subproject 2, we will focus on the investigation of carbapenemase, ESBL, and AmpC -lactamase production among the CRE isolates, sequencing and typing for the plasmid encoding carbapenemase gene, and determining the resistant mechanisms of fluoroquinolones among carbapenemase-producing CRE. In subproject 3, we will focus on the investigation of outer membrane changes and expression of efflux pump.carbapenem 抗藥性腸內菌metallo--lactamase 1NDM-1KPCcarbapenem-resistant Enterobacteriaceaemetallo--lactamase 1NDM-1KPC