Correlation of rpoB mutations with minimal inhibitory concentration of rifampin and rifabutin in Mycobacterium tuberculosis in an HIV/AIDS endemic setting, South Africa
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Authors
Rukasha, Ivy
Said, Halima M.
Omar, Shaheed Vally
Koornhof, Hendrik
Dreyer, Andries W.
Musekiwa, Alfred
Moultrie, Harry
Hoosen, Anwar A.
Kaplan, Gilla
Fallows, Dorothy
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Volume Title
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Frontiers Research Foundation
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.
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Keywords
rpoB, Rifampicin, Minimum inhibitory concentration, HIV/AIDS, Point mutation, Tuberculosis (TB), Rifabutin (RFB), Minimum inhibitory concentrations (MIC), Multidrug-resistant (MDR), Mycobacterium tuberculosis (MTB), Human immunodeficiency virus (HIV), Acquired immune deficiency syndrome (AIDS), South Africa (SA)
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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.