鮑氏不動桿菌分離菌株β-lactam類抗生素抗藥性染色體基因型研究

Genotyping of OXA carbapenemases genes of Multidrug Resistant Acinetobacter baumannii Isolates

蔡仰陞(Yang-Sheng Tsai)

指導教授 ： 張懿欣

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00164

摘要

近年來微生物的抗藥性問題，已成為人類健康的重要議題，特別是因院內感染所造成的。自從抗生素發明以來，人類不斷濫用抗生素，使得細菌為了生存，得以藉由不斷演化，產生抗藥性尋求存活的機會。細菌形成抗藥性的結果導致疾病，死亡的增加，和保健費用的浪費。鮑氏不動桿菌（Acinetobacter baumannii）為院內感染常見的伺機性菌株。抗藥性鮑氏不動桿菌的產生，使得在治療上更具挑戰。近來許多醫院的鮑氏不動桿菌群突發分析，皆與對碳醯胺基酶（carbapenemases）類抗生素產生抗藥性有關。鮑氏不動桿菌主要透過產生碳醯胺基酶來對抗碳醯胺基類抗生素。碳醯胺基酶可分為四群OXA23-like; OXA24-like; OXA51-like;及OXA58-like。本篇研究主題是探討全抗藥性鮑氏不動桿菌的碳醯胺基酶基因分佈情形。本篇研究共蒐集192株全抗藥性鮑氏不動桿菌菌株，利用多重聚合酶連鎖反應（multiplex polymerase chain reaction；PCR）技術分析其染色體碳醯胺基酶之基因型。結果發現所有分離菌株均有OXA51-like基因；185株帶有OXA23-like加上OXA51-like基因；7株僅有OXA51-like基因；1株帶有OXA24-like加上OXA51-like基因；沒有發現OXA58-like基因。此外碳醯胺基酶基因型態其分佈情形與年齡、性別、是否為ICU病房及細菌源自哪些檢體並無直接關係。
本研究發現染色體帶有OXA24-like基因的全抗藥性鮑氏不動桿菌[Pandrug-Resistant Acinetobacter baumannii（PDRAB）]比不帶OXA24-like基因的菌株對Tigecycline的抗藥作用較強其最效抑制濃度（MIC）達8 µg/ml；而帶有OXA51-like、OXA23-like的PDRAB仍有近80 %對Tigecycline仍具敏感性，其MIC為2~4 µg/ml。

關鍵字

鮑氏不動桿菌 ； 抗藥性 ； 染色體基因型

並列摘要

The emergence and rapid spread of the important nosocomial pathogens drug-resistant Acinetobacter spp., in particular Acinetobacter baumannii (A. baumannii), are of great concern worldwide. More than half of the drug-resistant Acinetobacter spp. are resistant to at least 3 classes of antibiotics, and designated as multidrug-resistant (MDR) Acinetobacter spp.. The antimicrobial agent carbapenems have been relied upon for treating infections caused by MDR A. baumannii. However, carbapenems resistance in Acinetobacter spp. is particularly a significant public health concern, leaving clinicians with few therapeutic options remaining. The OXA carbapenem-hydrolysing β-lactamases (carbapenemases; belonging to molecular class D OXA enzymes) of Acinetobacter spp. are divided into 4 phylogenetic subgroups: OXA23-like (subgroup 1), OXA24-like (subgroup 2), OXA51-like (subgroup 3) and OXA58 (sharing less than 50% amino acid identity to the other subgroups). In this study, 192 PDR A. baumannii isolates were collected, and distribution of genes encoding the 4 subgroups of OXA carbapenemases among the isolates was examined by multiplex polymerase chain reaction. All the 192 isolates have OXA51-like gene while no OXA58-like gene was detected. The frequency of OXA23-like and OXA24-like gene was 96.35% and 0.52%, respectively. No significant association between the genotyping of A. baumannii isolates and clinical parameters was observed. Our results provided the genotypic information of drug-resistant A. baumannii isolated in central Taiwan which, hopeful, would be beneficial to the understanding of microbial genetic background of antibiotic resistance as well as to the controlling the cognate infection of MDR A. baumannii in medical care and service.

並列關鍵字

OXA carbapenemases genes ； Multidrug Resistant Acinetobacter baumannii

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