결핵균에서 gyrA 유전자 돌연변이에 따른 Fluoroquinolone계 약제들의 교차내성 1 대한결핵협회 결핵연구원, 2 성균관대학교 의과대학 내과학교실 삼성서울병원 호흡기내과, 3 서울대학교 의과대학 미생물학교실, 4 연세대학교 의과대학 미생물학교실 박영길 1 , 박찬홍 1 , 고원중 2 , 권오정 2 , 김범준 3 , 국윤호 3 , 조상래 4 , 장철훈 1 , 배길한 Background : Fluoroquinolone drugs are an important anti-tuberculous agent for the treatment of multi-drug resistant tuberculosis. However, many drugs belonging to the fluoroquinolones have different cross resistance to each other. Methods : Sixty-three ofloxacin (OFX) resistant and 10

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... -susceptible M. tuberculosis isolates were selected, and compared for their cross resistance using a proportion method on Lowenstein-Jensen media, containing ofloxacin (OFX), ciprofloxacin (CIP), levofloxacin (LVX), moxifloxacin (MXF), gatifloxacin (GAT) and sparfloxacin (SPX), at concentrations ranging from 0.5 to 3µg/ml. DNA extracted from the isolates was directly sequenced after amplifying from the gyrA and gyrB genes. Results : The 63 OFX resistant M. tuberculosis isolates showed complete cross resistance to CIP, but only 90.5, 44.4, 36.5 and 46.0% to LVX, MXF, GAT, and to SPX, respectively. Fifty-one of the isolates (81.0%) had point mutations in codons 88, 90, 91 and 94 in gyrA, which are known to be correlated with OFX resistance. The Gly88Ala, Ala90Valand Asp94Ala mutations in gyrA showed a tendency to be susceptible to MXF, GAT and SPX. Only 4 isolates had mutations in the gyrB gene, which did not affect the OFX resistance. Conclusion : About 60% of the OFX resistant M. tuberculosis isolates were susceptible to GAT, SPX and MXF. These fluoroquinolones may be useful in the treatment of TB patients showing OFX resistance. (Tuberc Respir Dis 2005; 59: 250-256)