2018-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/713158摘要：肺炎黴漿菌(Mycoplasma pneumoniae，簡稱黴漿菌)造成之非典型肺炎為幼童肺炎主要病因之一，目前約有10-30%的兒童社區型肺炎是由肺炎黴漿菌(Mycoplasma pneumoniae)感染所引起。在全面接種肺炎鏈球菌(Streptococcus pneumoniae)疫苗以後，肺炎黴漿菌的重要性將與日俱增。而抗藥性的出現是治療肺炎黴漿菌一個很大的問題，尤其在亞洲巨環內酯類 (macrolides)抗藥性的比例高達20-100%。產生抗藥性肺炎黴漿菌的成因主要是菌株本身的23S核糖體核糖核酸(rRNA)上V區域(domain V)基因某些位點產生點突變(point mutations)。我們在2013年的研究中，於台灣本土之肺炎黴漿菌株中測得會造成抗藥性的點突變(A2063G)，抗藥性比例高達23%。較近年代本土菌株的抗藥性可能已經增機，但確實比例則仍未知。針對巨環內酯類抗藥性黴漿菌的治療，目前大部分仍將巨環內酯類列為第一線藥物。成人的二線藥物包含四環素類（tetracyclines）或是喹諾酮類（fluoroquinolones）之抗生素，但是這兩類藥物在兒童的使用皆有安全性的疑慮。不過，近年來已有越來越多研究顯示多西環素(doxycycline)與其他四環黴素類藥物不同，它不會造成牙齒的色素沉著。目前缺乏針對兒童的抗藥性黴漿菌感染，各種藥物治療療效的臨床試驗，最佳藥物治療目前仍屬未知。本計畫分成兩部分，一方面將利用PCR的方法來偵測近年台灣兒童抗藥性黴漿菌感染的比例，並利用多重位址重複變異序列分析(MLVA)來鑑定台灣近年流行的產生抗藥性肺炎黴漿菌株之基因分型，藉以建立菌株間的種源關係。另外，本計畫也將比較使用多西環素(doxycycline)與阿齊黴素(azithromycin)治療兒童肺炎黴漿菌感染之療效。本計畫完成後，可以了解台灣地區肺炎黴漿菌株之流行病學，且能提供臨床藥物治療之依據。<br> Abstract: Mycoplasma pneumoniae accounts for 10–30% of community-acquired pneumonia (CAP) in children. Proportionally, M. pneumoniae has become the most important pathogen for childhood pneumonia after the wide-spread use of Streptococcus pneumoniae vaccines. M. pneumoniae is routinely treated with antibiotics, and the macrolides antibiotics are the drug of choice for M. pneumonia infection. However, macrolides-resistance rates have increased to 20 and 100% in Asia. In our previous studies, the most common mutation point, A2063G, was detected from 23% of local strains in Taiwan. The evolution and spreading of Mycoplasma in Taiwan and different countries are unknown. Genotyping based on multiple-locus variable-number tandem-repeat and resistance analysis (MLVA) will be used to study the classification and possibly the evolution of M. pneumoniae strains.While the macrolide-resistance is increasing, the optimal therapy remains unclear. Both tetracyclines and fluoroquinolones showed promises in treating macrolide-resistant M. pneumoniase in adults. However, their use in children is not recommended due to safety concerns. Recently, evidence are accumulating that doxycycline, unlike other tetracyclines, does not cause staining of teeth. In the current study, we are going to carry out a randomized control trial to compare the efficacy and safety of doxycycline against macrolide-resistant M. pneumoniae. On the other hand, we are going to update the macrolide-resistant rates in Taiwan and analyze M. pneumoniae strains in Taiwan by MLVA. By using this rapid and highly discriminatory tool, we could provide more reliable information about the relationship between resistance strains of M. pneumoniae in Taiwan and across countries.肺炎黴漿菌巨環內酯類抗生素抗藥性多重位址重複變異序列分析多西黴素Mycoplasma pneumoniaemacrolideresistanceMLVAdoxycycline