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Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa

Treatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibi...

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Autores principales: Rukasha, Ivy, Said, Halima M., Omar, Shaheed V., Koornhof, Hendrik, Dreyer, Andries W., Musekiwa, Alfred, Moultrie, Harry, Hoosen, Anwar A., Kaplan, Gilla, Fallows, Dorothy, Ismail, Nazir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136537/
https://www.ncbi.nlm.nih.gov/pubmed/27994580
http://dx.doi.org/10.3389/fmicb.2016.01947
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author Rukasha, Ivy
Said, Halima M.
Omar, Shaheed V.
Koornhof, Hendrik
Dreyer, Andries W.
Musekiwa, Alfred
Moultrie, Harry
Hoosen, Anwar A.
Kaplan, Gilla
Fallows, Dorothy
Ismail, Nazir
author_facet Rukasha, Ivy
Said, Halima M.
Omar, Shaheed V.
Koornhof, Hendrik
Dreyer, Andries W.
Musekiwa, Alfred
Moultrie, Harry
Hoosen, Anwar A.
Kaplan, Gilla
Fallows, Dorothy
Ismail, Nazir
author_sort Rukasha, Ivy
collection PubMed
description Treatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibitors because of reduced induction of CYP3A4. This study sought to determine the proportion of RFB susceptible isolates among RIF-resistant strains in a high HIV prevalence setting in South Africa. In addition, the study explored the association between rpoB mutations and minimum inhibitory concentrations (MIC) of RIF and RFB. A total of 189 multidrug resistant (MDR) Mycobacterium tuberculosis isolates from the Centre for Tuberculosis repository were analyzed. The MICs were determined using a MYCOTB Sensititre plate method and the rpoB gene was sequenced. Of the 189 MDR isolates, 138 (73%) showed resistance to both RIF and RFB, while 51 (27%) isolates were resistant to RIF but retained susceptibility to RFB. The S531L was the most frequent rpoB point mutation in 105/189 (56%) isolates, followed by H526Y in 27/189 (14%) isolates. Resistance to both RIF and RFB was found predominantly in association with mutations S531L (91/105, 87%), H526Y (20/27, 74%), and H526D (15/19, 79%), while D516V (15/17, 88%), and L533P (3/4, 75%) were found in RIF-resistant, RFB-susceptible isolates. This study has shown that up to 27% of MDR-TB patients in South Africa may benefit from a treatment regimen that includes RFB.
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spelling pubmed-51365372016-12-19 Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa Rukasha, Ivy Said, Halima M. Omar, Shaheed V. Koornhof, Hendrik Dreyer, Andries W. Musekiwa, Alfred Moultrie, Harry Hoosen, Anwar A. Kaplan, Gilla Fallows, Dorothy Ismail, Nazir Front Microbiol Microbiology Treatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibitors because of reduced induction of CYP3A4. This study sought to determine the proportion of RFB susceptible isolates among RIF-resistant strains in a high HIV prevalence setting in South Africa. In addition, the study explored the association between rpoB mutations and minimum inhibitory concentrations (MIC) of RIF and RFB. A total of 189 multidrug resistant (MDR) Mycobacterium tuberculosis isolates from the Centre for Tuberculosis repository were analyzed. The MICs were determined using a MYCOTB Sensititre plate method and the rpoB gene was sequenced. Of the 189 MDR isolates, 138 (73%) showed resistance to both RIF and RFB, while 51 (27%) isolates were resistant to RIF but retained susceptibility to RFB. The S531L was the most frequent rpoB point mutation in 105/189 (56%) isolates, followed by H526Y in 27/189 (14%) isolates. Resistance to both RIF and RFB was found predominantly in association with mutations S531L (91/105, 87%), H526Y (20/27, 74%), and H526D (15/19, 79%), while D516V (15/17, 88%), and L533P (3/4, 75%) were found in RIF-resistant, RFB-susceptible isolates. This study has shown that up to 27% of MDR-TB patients in South Africa may benefit from a treatment regimen that includes RFB. Frontiers Media S.A. 2016-12-05 /pmc/articles/PMC5136537/ /pubmed/27994580 http://dx.doi.org/10.3389/fmicb.2016.01947 Text en Copyright © 2016 Rukasha, Said, Omar, Koornhof, Dreyer, Musekiwa, Moultrie, Hoosen, Kaplan, Fallows and Ismail. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Rukasha, Ivy
Said, Halima M.
Omar, Shaheed V.
Koornhof, Hendrik
Dreyer, Andries W.
Musekiwa, Alfred
Moultrie, Harry
Hoosen, Anwar A.
Kaplan, Gilla
Fallows, Dorothy
Ismail, Nazir
Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa
title Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa
title_full Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa
title_fullStr Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa
title_full_unstemmed Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa
title_short Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa
title_sort correlation of rpob mutations with minimal inhibitory concentration of rifampin and rifabutin in mycobacterium tuberculosis in an hiv/aids endemic setting, south africa
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136537/
https://www.ncbi.nlm.nih.gov/pubmed/27994580
http://dx.doi.org/10.3389/fmicb.2016.01947
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