期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 65, 期 5, 页码 897-900出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkq047
关键词
XDR-TB; ofloxacin; kanamycin
资金
- University of Cape Town
- National Health Laboratory Service Research Trust
- Medical Research Council, South Africa
- Deutscher Akademischer Austausch Dienst
- Wellcome Trust [072070]
The use of rapid molecular assays for the detection of resistance to second-line drugs would significantly decrease the time delay in diagnosing drug-resistant tuberculosis (TB) that is associated with conventional phenotypic drug susceptibility testing. In this study, multiplex allele-specific (MAS)-PCR assays designed to detect the GyrA D94G and rrs A1401G mutations were evaluated for detection of ofloxacin and kanamycin resistance. GyrA D94G and rrs A1401G MAS-PCR assays were carried out on 288 Mycobacterium tuberculosis isolates. Phenotypic drug susceptibility testing of ofloxacin and kanamycin was performed on selected multidrug-resistant TB isolates using the indirect proportions method. MAS-PCR assays detected GyrA D94G and rrs A1401G mutations in phenotypically resistant isolates with clinical sensitivities of 54.5% (6 of 11) and 90.0% (9 of 10), respectively, and specificities of 100% were obtained for both assays. A GyrA A90V mutation was identified in 4 of 11 (36.4%) ofloxacin-resistant isolates that did not carry a D94G substitution. Rapid genotypic assays designed to detect GyrA D94G and A90V mutations and rrs A1401G mutations could detect up to 90.0% of extensively drug-resistant (XDR)-TB in the Western Cape region. The use of these assays in the clinical setting would significantly reduce the time to diagnosis of XDR-TB, enabling the administration of appropriate treatment regimens at the outset of therapy.
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