具carbapenem抗藥性鮑氏不動桿菌(Acinetobacter baumannii)之抗藥性與傳播機轉及醫院流行病學

Hospital epidemiology and mechanisms for resistance and transmission of carbapenem-resistant Acinetobacter baumannii

盧柏樑(Po-Liang Lu)

指導教授 ： 林勝豐

高雄醫學大學/醫學院/醫學研究所/博士(2011年)

摘要

鮑氏不動桿菌(Acinetobacter baumannii)在臨床上由各種檢體分離出來的比率在近二十年來日益增加，鮑氏不動桿菌除了因在醫院內的盛行率增加而受到重視外，具有多重抗藥性的鮑氏不動桿菌感染也造成臨床上治療的困難。目前發現的carbapenem抗藥性機轉以carbapenemases為主，包括OXA, IMP, VIM等酵素，但其它機轉如外膜蛋白缺乏 (outer membrane protein loss)則較少有文獻研究，其相關之基因調控與流行病學上之重要性有待研究。本研究發現南台灣主要有OXA-72可藉由質體傳播，並有多種carbapenemases (OXA-23-like, OXA-24-like, OXA-51-like, OXA-58-like, VIM and IMP types)存在。Insertion sequence ISAba1 可以做為OXA-23-like, OXA-51-like, 與 AmpC type enzymes 的promoter，而較少被研究的CarO外膜蛋白改變在本研究中發現被ISAba1插入而不表現，因而carbapenem不能由CarO外膜蛋白進入菌株發生作用。在臨床研究顯示具有carbapenem抗藥性的鮑氏不動桿菌可以經病人轉院與菌株傳播在醫院中增加，在流行病學上，抗生素的選擇壓力 (antibiotic selection pressure)也和此種抗藥菌種的增加有相關。由多重抗藥鮑氏不動桿菌在病房內之流行病學顯示:電腦滑鼠與鍵盤會有MRSA (methicillin resistant Staphylococcus aureus)與鮑氏不動桿菌汙染，但在非群突發時期與有足夠洗手遵從度時，造成病患感染的機率低。本研究確認了亞太地區首件全院性的具OXA-72基因與ISAba1 preceding OXA-51-like基因機轉之extensively drug resistant A.baumannii (XDRAb)群突發後，進一步了解病人身上的XDRAb帶菌情況與其周遭環境污染和XDRAb的散播有關。落實感控教育、個人房隔離與環境清潔可以在不關閉病房的情況下在短期內控制住群突發。面對carbapenem抗藥性之威脅，深入了解抗藥性與傳播之機轉、醫院流行病學與相關感控措施將有助於預防與處置多重抗藥性菌種之流行。

關鍵字

鮑氏不動桿菌 ； 抗藥性 ； 外膜蛋白 ； carbapenemase

並列摘要

Acinetobacter baumannii was increasingly isolated from clinical specimens. It became a serious concern because of the increasing prevalence in hospital infections and its multiple drug resistance. Most carbapenem resistance mechanisms of A. baumannii are due to carbapenemases which included OXA, IMP and VIM enzymes. Other mechanisms including outer membrane protein loss and efflux pump required further investigation. The molecular basis of outer membrane protein loss and its importance in epidemiology were investigated in this study. This study found OXA-72 carbapenemase which could be carried by plasmids has become a major mechanism of carbapenem resistance. Multiple carbapenemases, including OXA-23-like, OXA-24-like, OXA-51-like, OXA-58-like, VIM and IMP types carbapenemases were seen in southern Taiwan. Insertion sequence ISAba1 can function as a promoter for OXA-23-like, OXA-51-like, and AmpC type enzymes, and can also interrupt the CarO gene to cause this outer membrane loss. Carbapenem resistant A. baumannii can introduce into hospital settings through patient transfer and clonal transmission. Antibiotic selection pressure is epidemiologically associated with the drug resistance. In non-outbreak situation, MRSA (methicillin resistant Staphylococcus aureus) and A. baumannii may contaminate the computer interfaces, including keyboards and mice, in hospital wards. With good hand hygiene compliance, the computer isolates were not related with clinical infection isolates. When the first outbreak of extensively drug resistant A.baumannii (XDRAb) with OXA-72 and ISAba1 preceding OXA-51-like mechanisms was identified, the further investigation confirmed the environmental contamination and patient colonization status played important role in transmission. With intensive education, private room isolation and dedicated room cleaning, such an outbreak can be controlled without closure of wards. Facing the threat of carbapenem resistance, understanding the mechanisms of resistance and transmission and knowing the clinical epidemiology and infection control measures were important to prevent and manage the epidemic of multiple drug resistant pathogens.

並列關鍵字

Acinetobacter baumannii ； resistance ； outer membrane protein ； carbapenemase

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