Cross Resistance of Fluoroquinolone Drugs on gyrA Gene Mutation in Mycobacterium tuberculosis.
10.4046/trd.2005.59.3.250
- Author:
Young Kil PARK
1
;
Chan Hong PARK
;
Won Jung KOH
;
O Jung KWON
;
Bum Jun KIM
;
Yoon Hoh KOOK
;
Sang Nae CHO
;
Chul hun CHANG
;
Gill Han BAI
Author Information
1. Korean Institute of Tuberculosis, Seoul, Korea. gbai@hotmail.com
- Publication Type:Original Article
- Keywords:
Mycobacterium tuberculosis;
Fluoroquinolones;
Cross resistance;
gyrA;
Genotypes
- MeSH:
Ciprofloxacin;
Codon;
DNA;
Fluoroquinolones;
Genotype;
Humans;
Levofloxacin;
Mycobacterium tuberculosis*;
Mycobacterium*;
Ofloxacin;
Point Mutation;
Tuberculosis;
Tuberculosis, Multidrug-Resistant
- From:Tuberculosis and Respiratory Diseases
2005;59(3):250-256
- CountryRepublic of Korea
- Language:Korean
-
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.
