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The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis.
- Source :
- Journal of Antimicrobial Chemotherapy (JAC); Oct2018, Vol. 73 Issue 10, p2667-2674, 8p
- Publication Year :
- 2018
-
Abstract
- <bold>Background: </bold>Use of the Xpert MTB/RIF assay has increased the number of people diagnosed with rifampicin-resistant tuberculosis (RR-TB), especially in South Africa where Xpert is now the initial diagnostic for individuals with TB symptoms. We hypothesized that a proportion of RR-TB patients determined by Xpert can be treated with a rifabutin-containing regimen.<bold>Methods: </bold>Rifabutin susceptibility by rpoB mutation was assessed in 349 individuals from South Africa and 172 from Belgium. rpoB polymorphisms were identified by Sanger sequencing. Rifampicin and rifabutin susceptibility was assessed phenotypically. A systematic review was performed to comprehensively collate information on rifabutin susceptibility by rpoB polymorphism. Rifabutin susceptibility was assigned to rpoB polymorphisms based on their positive likelihood ratios and ORs.<bold>Results: </bold>One hundred and twelve rpoB polymorphisms (67.9% from literature) were identified from all 2045 RR-TB patients, of which 17 polymorphisms could be classified as susceptible/resistant to rifabutin. Eleven polymorphisms were associated with rifabutin susceptibility. The 516GTC mutation was the most common, representing 70% (South Africa) and 76% (Belgium) of all rifabutin-susceptible isolates. At a population level, the 11 polymorphisms associated with rifabutin susceptibility occurred in 33.2% and 16.6% of all South African and Belgian patients diagnosed with RR-TB, respectively.<bold>Conclusions: </bold>Identification of the exact rpoB polymorphism leading to the diagnosis of RR-TB has the potential to allow inclusion of rifabutin in the treatment regimen of a substantial proportion of RR-TB patients. A randomized controlled trial evaluating the efficacy of a rifabutin-containing TB treatment regimen in these selected patients is needed to provide the evidence required for a change in policy. [ABSTRACT FROM AUTHOR]
- Subjects :
- RIFAMPIN
TUBERCULOSIS treatment
MULTIDRUG resistance
BIOLOGICAL assay
DISEASE susceptibility
MEDICAL care
THERAPEUTICS
ANTIBIOTICS
ANTI-infective agents
BACTERIAL proteins
COMPARATIVE studies
GENETIC polymorphisms
RESEARCH methodology
MEDICAL cooperation
MICROBIAL sensitivity tests
GENETIC mutation
MYCOBACTERIUM tuberculosis
RESEARCH
RESEARCH funding
TRANSFERASES
SYSTEMATIC reviews
EVALUATION research
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 73
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 131920681
- Full Text :
- https://doi.org/10.1093/jac/dky248