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dc.contributor.author | Ismail, Nazir Ahmed![]() |
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dc.contributor.author | Said, H.M.![]() |
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dc.contributor.author | Rodrigues, C.![]() |
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dc.contributor.author | Omar, Shaheed Vally![]() |
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dc.contributor.author | Ajbani, K.![]() |
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dc.contributor.author | Sukhadiad, N.![]() |
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dc.contributor.author | Kohl, T.A.![]() |
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dc.contributor.author | Niemann, S.![]() |
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dc.contributor.author | Kranzer, K.![]() |
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dc.contributor.author | Diels, M.![]() |
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dc.contributor.author | Rigouts, L.![]() |
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dc.contributor.author | Rusch-Gerdes, S.![]() |
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dc.contributor.author | Siddiqi, S.![]() |
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dc.date.accessioned | 2019-07-22T12:20:49Z | |
dc.date.issued | 2019-05 | |
dc.description.abstract | To conduct a multicentre study to establish the critical concentration (CC) for clofazimine (CFZ) for drug susceptibility testing (DST) of Mycobacterium tuberculosis on the MGIT™960™ system using the distribution of minimum inhibitory concentrations (MIC) and genotypic analyses of Rv0678 mutations. In phase I of the study, the MIC distribution of laboratory strains (H37Rv and in vitro-selected Rv0678 mutants) and clinical pan-susceptible isolates were determined (n = 70). In phase II, a tentative CC for CFZ (n = 55) was proposed. In phase III, the proposed CC was validated using clinical drug-resistant tuberculosis (DR-TB) isolates stratified by Rv0678 mutation (n = 85). The MIC distribution of CFZ for laboratory and clinical pan-susceptible strains ranged between 0.125 μg/ml and 0.5 μg/ml. As the MIC values of DR-TB isolates used for phase II ranged between 0.25 μg/ml and 1 μg/ml, a CC of 1 μg/ml was proposed. Validation of the CC in phase III showed that probably susceptible and probably resistant Rv0678 mutants overlapped at 1 μg/ml. We therefore recommend a CC of 1 μg/ml, with additional testing at 0.5 μg/ml to define an intermediate category. This was the first comprehensive study to establish a CC for routine phenotypic DST of CFZ using the MGIT960 system to guide therapeutic decisions. | en_ZA |
dc.description.department | Medical Microbiology | en_ZA |
dc.description.embargo | 2019-11-01 | |
dc.description.librarian | hj2019 | en_ZA |
dc.description.uri | https://www.ingentaconnect.com/content/iuatld/ijtld | en_ZA |
dc.identifier.citation | Ismail, N.A., Said, H.M., Rodrigues, C. et al. 2019, 'Multicentre study to establish interpretive criteria for clofazimine drug susceptibility testing', International Journal of Tuberculosis and Lung Disease, vol. 23, no. 5 , pp. 594-599. | en_ZA |
dc.identifier.issn | 1027-3719 (print) | |
dc.identifier.issn | 1815-7920 (online) | |
dc.identifier.other | 10.5588/ijtld.18.0417 | |
dc.identifier.uri | http://hdl.handle.net/2263/70779 | |
dc.language.iso | en | en_ZA |
dc.publisher | International Union Against Tuberculosis and Lung Disease | en_ZA |
dc.rights | International Union Against Tuberculosis and Lung Disease. | en_ZA |
dc.subject | Critical concentration (CC) | en_ZA |
dc.subject | Clofazimine (CFZ) | en_ZA |
dc.subject | Drug susceptibility testing (DST) | en_ZA |
dc.subject | Mycobacterium tuberculosis (MTB) | en_ZA |
dc.subject | Minimum inhibitory concentrations (MIC) | en_ZA |
dc.subject | Genotypic analyses | en_ZA |
dc.subject | Drug-resistant tuberculosis (DR-TB) | en_ZA |
dc.subject | 960™ | en_ZA |
dc.subject | MGIT™ | en_ZA |
dc.title | Multicentre study to establish interpretive criteria for clofazimine drug susceptibility testing | en_ZA |
dc.type | Postprint Article | en_ZA |