Multicentre study to establish interpretive criteria for clofazimine drug susceptibility testing

Show simple item record Ismail, Nazir Ahmed Said, H.M. Rodrigues, C. Omar, Shaheed Vally Ajbani, K. Sukhadiad, N. Kohl, T.A. Niemann, S. Kranzer, K. Diels, M. Rigouts, L. Rusch-Gerdes, S. Siddiqi, S. 2019-07-22T12:20:49Z 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 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.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

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