gyrA mutations and phenotypic susceptibility levels to ofloxacin and moxifloxacin in clinical isolates of Mycobacterium tuberculosis
dc.contributor.author | Sirgel F.A. | |
dc.contributor.author | Warren R.M. | |
dc.contributor.author | Streicher E.M. | |
dc.contributor.author | Victor T.C. | |
dc.contributor.author | Van helden P.D. | |
dc.contributor.author | Bottger E.C. | |
dc.date.accessioned | 2012-05-17T08:58:55Z | |
dc.date.available | 2012-05-17T08:58:55Z | |
dc.date.issued | 2012 | |
dc.description.abstract | Objectives: To compare mutations in the quinolone resistance-determining region of the gyrA gene and flanking sequences with the MICs of ofloxacin and moxifloxacin for Mycobacterium tuberculosis. Methods: The presence of mutations in 177 drug-resistant M. tuberculosis isolates was determined by DNA sequencing and the MICs quantified by MGIT 960. Results: Single nucleotide polymorphisms were detected at codons 94 (n = 30), 90 (n = 12), 91 (n = 3), 89 (n = 1), 88 (n = 1) and 80 (n = 1). Four isolates with double mutations D94G plus A90V (n = 2) and D94G plus D94N (n = 2) reflect mixed populations. Agreement between genotypic and phenotypic susceptibility was high (≥97%) for both drugs. Mutant isolates had an MIC 50 of 8.0 mg/L and an MIC 90 of >10 mg/L for ofloxacin compared with an MIC 50 and MIC 90 of 2.0 mg/L for moxifloxacin. Codons 94 and 88 were linked to higher levels of fluoroquinolone resistance compared with codons 90, 91 and 89. The MIC distributions for the wild-type isolates ranged from ≤0.5 to 2.0 mg/L for ofloxacin and from ≤0.125 to 0.25 mg/L for moxifloxacin. However, 96% of the isolates with genetic alterations had MICs ≤2.0 mg/L for moxifloxacin, which is within its achievable serum levels. Conclusions: This study provides quantitative evidence that the addition of moxifloxacin to extensively drug-resistant tuberculosis (XDR-TB) regimens based on a clinical breakpoint of 2.0 mg/L has merit. The use of moxifloxacin in the treatment of multidrug-resistant tuberculosis may prevent the acquisition of additional mutations and development of XDR-TB. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. | |
dc.identifier.citation | Journal of Antimicrobial Chemotherapy | |
dc.identifier.citation | 67 | |
dc.identifier.citation | 5 | |
dc.identifier.citation | 1088 | |
dc.identifier.citation | 1093 | |
dc.identifier.issn | 3057453 | |
dc.identifier.other | 10.1093/jac/dks033 | |
dc.identifier.uri | http://hdl.handle.net/10019.1/21016 | |
dc.subject | DNA topoisomerase (ATP hydrolysing) | |
dc.subject | DNA topoisomerase (ATP hydrolysing) A | |
dc.subject | moxifloxacin | |
dc.subject | ofloxacin | |
dc.subject | quinoline derived antiinfective agent | |
dc.subject | article | |
dc.subject | bacterium isolate | |
dc.subject | codon | |
dc.subject | DNA sequence | |
dc.subject | gene mutation | |
dc.subject | genetic susceptibility | |
dc.subject | limit of quantitation | |
dc.subject | Mycobacterium tuberculosis | |
dc.subject | nonhuman | |
dc.subject | phenotype | |
dc.subject | single nucleotide polymorphism | |
dc.subject | wild type | |
dc.title | gyrA mutations and phenotypic susceptibility levels to ofloxacin and moxifloxacin in clinical isolates of Mycobacterium tuberculosis | |
dc.type | Article |