Analysis of fluoroquinolone resistance in clinical isolates of Mycobacterium tuberculosis from India.
Clinical isolates of Mycobacterium tuberculosis (47 ofloxacin-susceptible and 71 ofloxacin-resistant) strains obtained from individual patients from various parts of India were analyzed for gyr A mutation in quinolone resistant determining region (QRDR). Most of the mutations were seen clustered in the codons 90, 94 and 95, which is a hot spot region of QRDR. The types of mutations were correlated with the in vitro susceptibility pattern of the strains to ofloxacin. The mutations: A90V was found coded for low-level resistance (MIC <or=16 microg/ml), D94A and D94V were coded for moderate level resistance (MIC 32-64 microg/ml) and S91P, D94G and D94N were coded for high level resistance (MIC >64 microg/ml) to ofloxacin. The resistance to fluoroquinolones was observed predominantly due to gyr A mutations. There were 2 highly resistant strains that did not show any mutations for gyr A, were further analyzed for gyr B mutations and were found negative for any mutations. However, there were two novel mutations, namely R68G and L109V, which were found in sensitive strain that did not code for any change in the susceptibility pattern and require further investigation.
Sulochana
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Tuberculosis Research Centre, Indian Council of Medical Research, Chennai, Tamil Nadu, India. sivamparam@yahoo.com
Narayanan
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Paramasivan
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CN
Suganthi
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Narayanan
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PR
D000995:Antitubercular Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D015242:Ofloxacin / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology
D000995:Antitubercular Agents; D015242:Ofloxacin; D027081:DNA Gyrase