rpoB Mutations Causing Discordant Rifampicin Susceptibility in Mycobacterium tuberculosis : Retrospective Analysis of Prevalence, Phenotypic, Genotypic, and Treatment Outcomes
Discordant genotypic/phenotypic rifampicin susceptibility testing in is a significant challenge, yet there are limited data on its prevalence and how best to manage such patients. Whether to treat isolates with mutations not conferring phenotypic resistance as susceptible or multidrug-resistant tube...
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Published in | Open forum infectious diseases Vol. 6; no. 4; p. ofz065 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Oxford University Press
01.04.2019
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Abstract | Discordant genotypic/phenotypic rifampicin susceptibility testing in
is a significant challenge, yet there are limited data on its prevalence and how best to manage such patients. Whether to treat isolates with
mutations not conferring phenotypic resistance as susceptible or multidrug-resistant tuberculosis (MDR-TB) is unknown. We describe phenotypic and genotypic characteristics of discordant isolates and clinical characteristics and treatment outcomes of affected patients in KwaZulu-Natal, South Africa.
We analyzed clinical isolates showing rifampicin resistance on GenoType MTBDR
while susceptible on 1% agar proportion method. We measured rifampicin minimum inhibitory concentrations (MICs) using Middlebrook 7H10 agar dilution and BACTEC MGIT 960. Sensititre MYCOTB plates were used for drug-susceptibility testing, and
gene sequencing was performed on all isolates. Local MDR-TB program data were reviewed for clinical information and patient outcomes.
Discordant isolates constituted 4.6% (60) of 1302 rifampicin-resistant cases over the study period. Of these, 62% remained susceptible to isoniazid and 98% remained susceptible to rifabutin. Rifampicin MICs were close to the critical concentration of 1 µg/mL (0.5-2 µg/mL) for 83% of isolates. The most frequent
mutations were Q513P (25.3%), D516V (19.2%), and D516Y (13.3%). Whereas 70% were human immunodeficiency virus infected, the mean CD4 count was 289 cells/mm
and 87% were receiving antiretroviral therapy. Standard therapy for MDR-TB was used and 53% achieved successful treatment outcomes.
Rifampicin-discordant TB is not uncommon and sequencing is required to confirm results. The high susceptibility to rifabutin and isoniazid and poor treatment outcomes with the current regimen suggest a potential utility for rifabutin-based therapy. |
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AbstractList | BACKGROUNDDiscordant genotypic/phenotypic rifampicin susceptibility testing in Mycobacterium tuberculosis is a significant challenge, yet there are limited data on its prevalence and how best to manage such patients. Whether to treat isolates with rpoB mutations not conferring phenotypic resistance as susceptible or multidrug-resistant tuberculosis (MDR-TB) is unknown. We describe phenotypic and genotypic characteristics of discordant isolates and clinical characteristics and treatment outcomes of affected patients in KwaZulu-Natal, South Africa. METHODSWe analyzed clinical isolates showing rifampicin resistance on GenoType MTBDRplus while susceptible on 1% agar proportion method. We measured rifampicin minimum inhibitory concentrations (MICs) using Middlebrook 7H10 agar dilution and BACTEC MGIT 960. Sensititre MYCOTB plates were used for drug-susceptibility testing, and rpoB gene sequencing was performed on all isolates. Local MDR-TB program data were reviewed for clinical information and patient outcomes. RESULTSDiscordant isolates constituted 4.6% (60) of 1302 rifampicin-resistant cases over the study period. Of these, 62% remained susceptible to isoniazid and 98% remained susceptible to rifabutin. Rifampicin MICs were close to the critical concentration of 1 µg/mL (0.5-2 µg/mL) for 83% of isolates. The most frequent rpoB mutations were Q513P (25.3%), D516V (19.2%), and D516Y (13.3%). Whereas 70% were human immunodeficiency virus infected, the mean CD4 count was 289 cells/mm3 and 87% were receiving antiretroviral therapy. Standard therapy for MDR-TB was used and 53% achieved successful treatment outcomes. CONCLUSIONSRifampicin-discordant TB is not uncommon and sequencing is required to confirm results. The high susceptibility to rifabutin and isoniazid and poor treatment outcomes with the current regimen suggest a potential utility for rifabutin-based therapy. Discordant genotypic/phenotypic rifampicin susceptibility testing in is a significant challenge, yet there are limited data on its prevalence and how best to manage such patients. Whether to treat isolates with mutations not conferring phenotypic resistance as susceptible or multidrug-resistant tuberculosis (MDR-TB) is unknown. We describe phenotypic and genotypic characteristics of discordant isolates and clinical characteristics and treatment outcomes of affected patients in KwaZulu-Natal, South Africa. We analyzed clinical isolates showing rifampicin resistance on GenoType MTBDR while susceptible on 1% agar proportion method. We measured rifampicin minimum inhibitory concentrations (MICs) using Middlebrook 7H10 agar dilution and BACTEC MGIT 960. Sensititre MYCOTB plates were used for drug-susceptibility testing, and gene sequencing was performed on all isolates. Local MDR-TB program data were reviewed for clinical information and patient outcomes. Discordant isolates constituted 4.6% (60) of 1302 rifampicin-resistant cases over the study period. Of these, 62% remained susceptible to isoniazid and 98% remained susceptible to rifabutin. Rifampicin MICs were close to the critical concentration of 1 µg/mL (0.5-2 µg/mL) for 83% of isolates. The most frequent mutations were Q513P (25.3%), D516V (19.2%), and D516Y (13.3%). Whereas 70% were human immunodeficiency virus infected, the mean CD4 count was 289 cells/mm and 87% were receiving antiretroviral therapy. Standard therapy for MDR-TB was used and 53% achieved successful treatment outcomes. Rifampicin-discordant TB is not uncommon and sequencing is required to confirm results. The high susceptibility to rifabutin and isoniazid and poor treatment outcomes with the current regimen suggest a potential utility for rifabutin-based therapy. |
Author | Mvelase, Nomonde R Mlisana, Koleka P Sibanda, Wilbert Ngozo, Jacqueline N Pillay, Melendhran Brust, James C M |
AuthorAffiliation | 3 Department of Biostatistics, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa 2 Department of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa 1 Department of Medical Microbiology, KwaZulu-Natal Academic Complex, National Health Laboratory Service, Durban, South Africa 4 Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa 5 Department of Health, KwaZulu-Natal Province, Pietermaritzburg, South Africa 6 Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York |
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Keywords | rpoB mutations rifampicin discordant TB |
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Snippet | Discordant genotypic/phenotypic rifampicin susceptibility testing in
is a significant challenge, yet there are limited data on its prevalence and how best to... BACKGROUNDDiscordant genotypic/phenotypic rifampicin susceptibility testing in Mycobacterium tuberculosis is a significant challenge, yet there are limited... |
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Title | rpoB Mutations Causing Discordant Rifampicin Susceptibility in Mycobacterium tuberculosis : Retrospective Analysis of Prevalence, Phenotypic, Genotypic, and Treatment Outcomes |
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