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Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa

BACKGROUND: Rifampicin resistance missed by commercial rapid molecular assays but detected by phenotypic assays may lead to discordant susceptibility results and affect patient management. OBJECTIVE: This study was conducted to evaluate the causes of rifampicin resistance missed by the GenoType MTBD...

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Detalles Bibliográficos
Autores principales: Mvelase, Nomonde R., Cele, Lindiwe P., Singh, Ravesh, Naidoo, Yeshnee, Giandhari, Jennifer, Wilkinson, Eduan, de Oliveira, Tulio, Swe-Han, Khine Swe, Mlisana, Koleka P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AOSIS 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982466/
https://www.ncbi.nlm.nih.gov/pubmed/36873290
http://dx.doi.org/10.4102/ajlm.v12i1.1975
Descripción
Sumario:BACKGROUND: Rifampicin resistance missed by commercial rapid molecular assays but detected by phenotypic assays may lead to discordant susceptibility results and affect patient management. OBJECTIVE: This study was conducted to evaluate the causes of rifampicin resistance missed by the GenoType MTBDRplus and its impact on the programmatic management of tuberculosis in KwaZulu-Natal, South Africa. METHODS: We analysed routine tuberculosis programme data from January 2014 to December 2014 on isolates showing rifampicin susceptibility on the GenoType MTBDRplus assay but resistance on the phenotypic agar proportion method. Whole-genome sequencing was performed on a subset of these isolates. RESULTS: Out of 505 patients with isoniazid mono-resistant tuberculosis on the MTBDRplus, 145 (28.7%) isolates showed both isoniazid and rifampicin resistance on the phenotypic assay. The mean time from MTBDRplus results to initiation of drug-resistant tuberculosis therapy was 93.7 days. 65.7% of the patients had received previous tuberculosis treatment. The most common mutations detected in the 36 sequenced isolates were I491F (16; 44.4%) and L452P (12; 33.3%). Among the 36 isolates, resistance to other anti-tuberculosis drugs was 69.4% for pyrazinamide, 83.3% for ethambutol, 69.4% for streptomycin, and 50% for ethionamide. CONCLUSION: Missed rifampicin resistance was mostly due to the I491F mutation located outside the MTBDRplus detection area and the L452P mutation, which was not included in the initial version 2 of the MTBDRplus. This led to substantial delays in the initiation of appropriate therapy. The previous tuberculosis treatment history and the high level of resistance to other anti-tuberculosis drugs suggest an accumulation of resistance.