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한국에서 분리된 리팜핀 내성 균주에서의 리파부틴 감수성 정도 및 관련 rpoB 유전자 돌연변이의 특성에 관한 연구

Other Titles
 The Proportion of Rifabutin-susceptible Strains among Rifampicin-resistant Isolates and Its Specific rpoB Mutations 
 류우진  ;  박영길  ;  김희진  ;  장철훈  ;  배길한  ;  김성규 
 Tuberculosis and Respiratory Diseases, Vol.59(3) : 257-265, 2005 
Journal Title
 Tuberculosis and Respiratory Diseases 
Issue Date
Background : Rifabutin (ansamycin) is a spiro-piperidyl rifamycin, which is highly active against Mycobacterium tuberculosis. It has been found that some clinical isolates of tubercle bacilli that are resistant to rifampicin are susceptible to rifabutin, with some patients with multi-drug resistant pulmonary tuberculosis having shown favorable clinical and bacteriological responses to the rifabutin. This study was conducted to find the proportion of rifabutin-susceptible strains among rifampicin-resistant isolates from Korean MDR-TB patients, and investigate the presence of specific rpoB mutations, which may confer resistance to rifampicin, but not to rifabutin. Methods : 201 rifampicin-resistant and 50 pan-susceptible M. tuberculosis isolates were randomly selected for this study. The isolates were retested at rifampicin and rifabutin concentrations of 0, 20, 40 and 80 µg/ml, respectively. The isolates that grew at and/or over a rifabutin concentration of 20 µg/ml were judged rifabutin-resistant. The rpoB gene was extracted from the isolates, and then amplified for direct sequencing to investigate specific rpoB mutations that conferred rifabutin- susceptibility but rifampicin-resistance. Results : Out of the 201 rifampicin-resistant M. tuberculosis, 41 strains (20.4%) were susceptible to rifabutin using the absolute concentration method on Lowenstein-Jensen media. The rpoB mutation types that showed susceptibility to rifabutin were Leu511Pro, Ser512Arg, Gln513Glu, Asp516Ala, Asp516Gly, Asp516Val, Asp516Tyr, Ser522Leu, His526Asn, His526Leu, His526Cys, Arg529Pro and Leu533Pro. A reverse hybridization technique was able to detect 92.5% of the rifabutin-susceptible isolates, with a specificity of 96.1% among 195 M. tuberculosis isolates with the rpoB mutation. Conclusions : Around 20% of the rifampicin-resistant isolates in Korea showed susceptibility to rifabutin, which was associated with some specific mutations of rpoB. Rifabutin could be used for the treatment of MDR-TB patients, especially when drug susceptibility testing reveals susceptibility to rifabutin.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sung Kyu(김성규)
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