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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks
PLoS ONE, Volume 8, No. 3, Article e59414, Year 2013
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Description
Genetically related Mycobacterium tuberculosis strains with alterations at codon 516 in the rpoB gene were observed amongst a substantial number of patients with drug resistant tuberculosis in the Eastern Cape Province (ECP) of South Africa. Mutations at codon 516 are usually associated with lower level rifampicin (RIF) resistance, while susceptibility to rifabutin (RFB) remains intact. This study was conducted to assess the rationale for using RFB as a substitution for RIF in the treatment of MDR and XDR tuberculosis outbreaks. Minimum inhibitory concentrations (MICs) of 34 drug resistant clinical isolates of M tuberculosis were determined by MGIT 960 and correlated with rpoB mutations. RFB MICs ranged from 0.125 to 0.25 μg/ml in the 34 test isolates thereby confirming phenotypic susceptibility as per critical concentration (CC) of 0.5 μg/ml. The corresponding RIF MICs ranged between 5 and 15 μg/ml, which is well above the CC of 1.0 μg/ml. Molecular-based drug susceptibility testing provides important pharmacogenetic insight by demonstrating a direct correlation between defined rpoB mutation and the level of RFB susceptibility. We suggest that isolates with marginally reduced susceptibility as compared to the epidemiological cut-off for wild-type strains (0.064 μg/ml), but lower than the current CC (≤0.5 μg/ml), are categorised as intermediate. Two breakpoints (0.064 μg/ml and 0.5 μg/ml) are recommended to distinguish between susceptible, intermediate and RFB resistant strains. This concept may assist clinicians and policy makers to make objective therapeutic decisions, especially in situations where therapeutic options are limited. The use of RFB in the ECP may improve therapeutic success and consequently minimise the risk of ongoing transmission of drug resistant M. tuberculosis strains. © 2013 Sirgel et al.
Authors & Co-Authors
Sirgel, Frederick Adriaan
South Africa, Stellenbosch
Stellenbosch University
Warren, Robin Mark
South Africa, Stellenbosch
Stellenbosch University
Böttger, Erik Christian
Switzerland, Zurich
Universität Zürich
Klopper, Marisa
South Africa, Stellenbosch
Stellenbosch University
Victor, Thomas Calldo
South Africa, Stellenbosch
Stellenbosch University
Van Helden, Paul D.
South Africa, Stellenbosch
Stellenbosch University
Statistics
Citations: 70
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1371/journal.pone.0059414
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Study Locations
South Africa