2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645741摘要：堪薩斯分枝桿菌 (Mycobacterium Kansasii) 為台灣常⾒見的⾮非結核分枝桿菌，在免疫不全的病患中會造成嚴重的肺部或瀰漫性感染，臨床表現與肺結核感染相近。︒｡其標準治療需合併使⽤用三種第⼀一線結核菌⽤用藥(isoniazid, rifampin, ethambutol)，⽽而療程⽐比肺結核感染要花費更⾧長的時間。︒｡先前研究發現，病患感染具rifampin 抗藥的菌株會提⾼高致死率，然⽽而⽬目前該菌藥敏測試並⾮非常規檢驗，往往在治療不理想後才考慮進⾏行藥敏檢驗。︒｡由於⽣生⾧長緩慢，傳統測試需⾧長時間才能判讀結果，無法提供嚴重感染或發⽣生藥物副作⽤用⽽而需調整處⽅方的病患即時性參考。︒｡在台灣某醫學中⼼心⼩小規模調查發現該院菌株第⼀一線⽤用藥抗藥性都超過20%，⽽而第⼆二線⽤用藥亦有5.4%-40.5%不等的抗藥性。︒｡⽬目前已知台灣堪薩斯分枝桿菌具抗藥性的菌株具群聚性，不過抗藥菌株間的分⼦子相關性以及抗藥性與病患治療預後並無進⼀一步研究。︒｡本試驗希望藉由台⼤大醫院過去(2000-2015 年)所分離的495 株堪薩斯分枝桿菌進⾏行藥敏測試，以了解⽬目前各藥物抗藥性以及與病患治療結果相關性，進⼀一步⽐比較抗藥菌株rpoB 基因序列並建⽴立抗rifampin 快速分⼦子診斷。︒｡我們將利⽤用脈衝式膠體電泳(Pulsed-field gel electrophoresis)以及多重基因座序列分型(Multilocus sequence typing)分析各菌株的分⼦子相關性並與MALDI-TOF(matrix-assistedlaser desorption ionization-time of flight)結果⽐比較，建⽴立相關性資料庫，以利後續快速分型並提供另⼀一種多重抗藥菌株快速鑑定的參考。<br> Abstract: Mycobacterium kansasii is an important pathogen causing pulmonary infection and disseminateddisease resembling tuberculosis in immunocompromized hosts. Increased disease burden andemerging of drug resistant strains are major challenge globally. Strains with rifampin resistance areassociated with treatment failure. However, antimicrobial susceptibility testing (AST) istime-consuming and not incorporated in the conventional laboratory. Molecular diagnostic tools fordetecting drug resistant tuberculosis are commercially available and M. kansasii shared similar drugresistant genes with M. tuberculosis. Besides, heterogeneity was observed among M. kansasiiisolates with a certain clone causing more human infections and bearing rifampin-resistant. Incurrent study, we determine AST of 495 isolates against traditional and newer treatment regimens.Mutation codons distribution on rpoB gene would be evaluated to develop molecular testing forrifampin resistance. Genetic relatedness of the isolates is performed by using PCR restrictionanalysis and pulsed-field gel electrophoresis. The results are compared with those of MALDI-TOFMS microbial typing and multilocus sequence typing. The results of AST, genotyping and clinicaloutcome would be clarified to seek potentially rapid diagnostic methods for identifying drug resistantor virulent strains from clinical isolates.