Correlation of rpoB mutations with minimal inhibitory concentration of rifampin and rifabutin in Mycobacterium tuberculosis in an HIV/AIDS endemic setting, South Africa

Show simple item record 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 Ahmed 2017-02-08T05:32:08Z 2017-02-08T05:32:08Z 2016-12-06
dc.description.abstract 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. en_ZA
dc.description.department Medical Microbiology en_ZA
dc.description.librarian am2017 en_ZA
dc.description.sponsorship The research was funded by a grant from the NIH (ROI A180737) to GK which was transferred to DF. en_ZA
dc.description.uri en_ZA
dc.identifier.citation Rukasha I, Said HM, Omar SV, Koornhof H, Dreyer AW, Musekiwa A, Moultrie H, Hoosen AA, Kaplan G, Fallows D and Ismail N (2016) Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa. Front. Microbiol. 7:1947. DOI: 10.3389/fmicb.2016.01947. en_ZA
dc.identifier.issn 1664-302X
dc.identifier.other 10.3389/fmicb.2016.01947
dc.language.iso en en_ZA
dc.publisher Frontiers Research Foundation en_ZA
dc.rights © 2016 Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). en_ZA
dc.subject rpoB en_ZA
dc.subject Rifampicin en_ZA
dc.subject Minimum inhibitory concentration en_ZA
dc.subject HIV/AIDS en_ZA
dc.subject Point mutation en_ZA
dc.subject Tuberculosis (TB) en_ZA
dc.subject Rifabutin (RFB) en_ZA
dc.subject Minimum inhibitory concentrations (MIC) en_ZA
dc.subject Multidrug resistant (MDR) en_ZA
dc.subject Mycobacterium tuberculosis (MTB) en_ZA
dc.subject Human immunodeficiency virus (HIV) en_ZA
dc.subject Acquired immune deficiency syndrome (AIDS) en_ZA
dc.subject South Africa (SA) en_ZA
dc.title Correlation of rpoB mutations with minimal inhibitory concentration of rifampin and rifabutin in Mycobacterium tuberculosis in an HIV/AIDS endemic setting, South Africa en_ZA
dc.type Article en_ZA

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