2011-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645317摘要：腸内菌屬中的的 E. coli、Klebsiella pneumoniae、Citrobacter、Serratia、 Enterobacter、以及Morganella是臨床上重要的致病菌；過去十年來，由於這些細 菌出現了藉由分泌extended-spectrum P-lactamase (ESBL)的抗藥性，造成臨床上 治療的極大困擾。一旦細菌能分泌ESBL， carbapenems類的抗生素就成為十分重 要的治療用藥。然而，許多研究發現近年來腸内菌屬的細菌對carbapenem抗生素的抗藥 性，有逐漸增加的現象。腸内菌屬細菌carbapenem抗藥性機轉主要包括同時有outer membrane的改變並分泌ESBL，同時有efflux pump的大量表現並分泌ESBL，同 時有outer membrane的改變並分泌AmpC P-lactamase，同時有efflux pump的大量 表現並分泌AmpC P-lactamase，以及分泌carbapenemase。而這些carbapenem的抗 藥性機轉中，以carbapenemase分泌的機轉，最引人重視。在腸内菌屬細菌所分泌 的 carbapenemases 中，又以 Kpneumoniae carbapenemase (KPC type)和 New-Delhi metallo-P-lactamase1 (NDM-1) enzymes，最令人矚目；其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。Carbapenem抗藥性腸内菌（CRE)的崛起，是醫界的一大隱憂；主要原因 是這一類的細菌，除了對carbapenems抗藥之外，幾乎同時藉由許多其他不同的抗 藥機轉，也對其他類的抗生素有抗藥性。在台灣，初步的監測資料顯示，CRE的盛行率逐年升高（雖然目前盛行率 仍低）。然而，截至目前為止，並沒有很好的研究來探討台灣地區CRE感染的臨床 表現、危險因子，也沒有研究探討CRE的抗藥機轉。我們的整合型計晝，主要是 為了回答上述的問題而設計。在子計晝一中，我們將利用case-control study的研究 設計，來探討發生CRE感染或移生的危險因子，描述CRE感染的臨床表現，並找 出不良預後的相關因子。在子計晝二中，我們著重於分析CRE的carbapenem抗藥 性是否導因於carbapenemases分泌。在子計晝三中，我們則著重於分析非 carbapenemase分泌的其他導致carbapenem抗藥性機轉，以及CRE對其他類抗生 素（含 fluoroquinolones, aminoglycosides,與 broad-spectrum cephalosporins)抗藥的 相關機轉。<br> Abstract: Bacteria belonging to Enterobacteriaceae, such as E. coli, Klebsiellapneumoniae, Enterobacter, Citrobacter, Serratia, and Morganella, are important human pathogens. In the past decade, treatment of infections caused by these bacteria has become challenging for the expression of extended-spectrum (3-lactamase (ESBL) (3-lactamase. In such situation, carbapenems will become the major drug to treat such kind of infection.However, recent study demonstrates that carbapenem resistance among Enterobacteriaceae increases gradually. The mechanisms of carbapenem resistance among Enterobacteriaceae include combination of ESBL-producing and outer membrane change or up-regulation of efflux pump, AmpC P-lactamase production of 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 carbapenemase found in Enterobacteriaceae, Klebsiella pneumoniae carbapenemase (KPC) and New-Delhi metallo-P-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, through various resistant mechanisms.This would results in very limited drug choice to treat CRE infection.In Taiwan, preliminary surveillance data demonstrated that prevalence of carbapenem resistance among Enterobacteriaceae has increase (although remains low). However, there is no study till now to investigate the clinical presentation of CRE infection and the genetric background of carbapenem resistance among CRE. The present project is designated to illuminate the above issues. In subproject one, we will focus on the risk factor to acquire CRE infection/colonization and the clinical presentation, including outcome analysis, of CRE infection using case-control study. In subproject 2, we will focus on the investigation of carbapenemase production among the CRE isolates. In subproject 3, we will focus on the investigation of other mechanism related to carbapenem resistance except carbapenemase production; and, since these isolates are usually also resistant to antibiotics beloning to other classes, mechanism related to resistance to other antibiotics, including aminoglycosides, fluoroquinolones, and broad-spectrum cephalosporins, among CRE isolates.carbapenem 抗藥性腸内菌metallo-P-lactamase 1NDM-1KPCcarbapenem-resistant Enterobacteriaceaemetallo-P-lactamase 1NDM-1KPC