Tuberc Respir Dis > Volume 59(3); 2005 > Article
Tuberculosis and Respiratory Diseases 2005;59(3):250-256.
DOI: https://doi.org/10.4046/trd.2005.59.3.250    Published online September 1, 2005.
Cross Resistance of Fluoroquinolone Drugs on gyrA Gene Mutation in Mycobacterium tuberculosis.
Young Kil Park, Chan Hong Park, Won Jung Koh, O Jung Kwon, Bum Jun Kim, Yoon Hoh Kook, Sang Nae Cho, Chul hun Chang, Gill Han Bai
1Korean Institute of Tuberculosis, Seoul, Korea. gbai@hotmail.com
2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
3Department of Microbiology, Seoul National University College of Medicine, Korea.
4Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
Abstract
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 pan-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 3microgram/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.
Key Words: Mycobacterium tuberculosis, Fluoroquinolones, Cross resistance, gyrA, Genotypes


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