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The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks
- Source :
- PLoS ONE, PLoS ONE, Vol 8, Iss 3, p e59414 (2013)
- Publication Year :
- 2013
- Publisher :
- Public Library of Science, 2013.
-
Abstract
- 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.
- Subjects :
- Bacterial Diseases
Rifabutin
lcsh:Medicine
Drug resistance
South Africa
Nucleic Acids
Tuberculosis, Multidrug-Resistant
Molecular Cell Biology
lcsh:Science
Multidisciplinary
biology
10179 Institute of Medical Microbiology
Drug Information
Bacterial Pathogens
Infectious Diseases
Medical Microbiology
Medicine
Public Health
Rifampin
medicine.drug
Research Article
Drugs and Devices
Tuberculosis
Drug Research and Development
Mutation, Missense
610 Medicine & health
1100 General Agricultural and Biological Sciences
Microbial Sensitivity Tests
Microbiology
Mycobacterium tuberculosis
Species Specificity
1300 General Biochemistry, Genetics and Molecular Biology
Microbial Control
Drug Resistance, Bacterial
medicine
Humans
Biology
business.industry
lcsh:R
Extensively drug-resistant tuberculosis
Correction
Drug Policy
rpoB
medicine.disease
biology.organism_classification
Virology
Pharmacodynamics
Pharmacogenetics
570 Life sciences
bacteria
lcsh:Q
business
Rifampicin
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....561b0671e7fdd4ee419aa8835688d587