Molecular Detection of Rifabutin-Susceptible Mycobacterium tuberculosis

Chen, Huang Yao; Yu, Ming Chih; Huang, Wei; Wu, Mei Hua; Chang, Yung Lin; Rai, Chien; Jou, Ruwen

doi:10.1128/jcm.00652-12

Cited by 16 publications

(17 citation statements)

References 9 publications

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“…In these studies, the most common mutations associated with RIF resistance/RFB susceptibility were associated with residues 516, 529, and 533. In our study, the proportion of RIF-resistant isolates that were RFB susceptible was only slightly higher than the proportions reported elsewhere (28%) (7,28,29). Mutations H526L, F514FF, D516V, and S522L were all associated with RIF resistance/RFB susceptibility patterns.…”

Section: Discussioncontrasting

confidence: 44%

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Profiling of rpoB Mutations and MICs for Rifampin and Rifabutin in Mycobacterium tuberculosis

et al. 2014

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bResistance to rifampin (RIF) and rifabutin (RFB) in Mycobacterium tuberculosis is associated with mutations within an 81-bp region of the rpoB gene (RIF resistance-determining region [RRDR]). Previous studies have shown that certain mutations in this region are more likely to confer high levels of RIF resistance, while others may be found in phenotypically susceptible isolates. In this study, we sought to determine the relationship between the MICs of RIF and RFB and rpoB RRDR mutations in 32 multidrug-resistant (MDR), 4 RIF-monoresistant, and 5 susceptible M. tuberculosis clinical isolates. The MICs were determined using the MGIT 960 system. Mutations in the rpoB RRDR were determined by Sanger sequencing. RpoB proteins with mutations S531L (a change of S to L at position 531), S531W, H526Y, and H526D and the double mutation D516A-R529Q were associated with high MICs for RIF and RFB. Five isolates carrying the mutations L511P, H526L, H526N, and D516G-S522L were found to be susceptible to RIF. Several mutations were associated with resistance to RIF and susceptibility to RFB (F514FF, D516V, and S522L). Whole-genome sequencing of two MDR isolates without rpoB RRDR mutations revealed a mutation outside the RRDR (V146F; RIF MIC of 50 g/ml). The implications of the polymorphisms identified in the second of these isolates in RIF resistance need to be further explored. Our study further establishes a correlation between the mutations and the MICs of RIF and, also, RFB in M. tuberculosis. Several rpoB mutations were identified in RIF-and RFB-susceptible isolates. The clinical significance of these findings requires further exploration. Until then, a combination of phenotypic and molecular testing is advisable for drug susceptibility testing.

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Section: Discussioncontrasting

confidence: 44%

“…Previous studies have shown a proportion of RIF-resistant isolates with susceptibility to RFB ranging from 13 to 26% (7,28,29). In these studies, the most common mutations associated with RIF resistance/RFB susceptibility were associated with residues 516, 529, and 533.…”

Section: Discussionmentioning

confidence: 61%

Profiling of rpoB Mutations and MICs for Rifampin and Rifabutin in Mycobacterium tuberculosis

et al. 2014

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“…However, RIF-resistant strains possessing certain mutations, mostly in codons 511, 516, 518, 522, 526, 533 may retain a level of in vitro susceptibility to RFB depending on the particular amino acid substitutions and have the potential to be clinically effective against RIF-resistant MTBC strains (11 – 21). Utilization of molecular assays capable of discriminating SNPs in the RRDR at the nucleotide level may allow for the prediction of culture-based drug susceptibility testing (CDST) results to RIF and RFB (14 – 15, 21 – 24). Owing to increased use of molecular diagnostics for detection of RIF resistance, an understanding of the relationship between different rpoB mutations and their association with differential resistance levels may be helpful to clinicians treating RIF-resistant TB or MDR-TB as a real-time complement to CDST which can take weeks to be completed.…”

Section: Introductionmentioning

confidence: 99%

Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex

Berrada

Lin

Rodwell

et al. 2016

Diagnostic Microbiology and Infectious Disease

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Cross-resistance in rifamycins has been observed in rifampin (RIF)-resistant Mycobacterium tuberculosis complex isolates; some rpoB mutations do not confer broad in vitro rifamycin resistance. We examined 164 isolates, of which 102 were RIF-resistant, for differential resistance between RIF and rifabutin (RFB). A total of 42 unique single mutations or combinations of mutations were detected. The number of unique mutations identified exceeded that reported in any previous study. RFB and RIF MICs up to 8 µg/ml by MGIT 960 were studied; the cut-off values for susceptibility to RIF and RFB were 1 µg/ml and 0.5 µg/ml, respectively. We identified 31 isolates resistant to RIF but susceptible to RFB with the mutations, D516V, D516F, 518 deletion, S522L, H526A, H526C, H526G, H526L and two dual mutations (S522L+K527R and H526S+K527R). Clinical investigations using RFB to treat MDR TB cases harboring those mutations are recommended.

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“…Studies from low HIV settings have reported that 13–26% of MDR-TB isolates show sensitivity to RFB (Chen et al, 2012; Jo et al, 2013; Schon et al, 2013). However, there is limited information on the frequency of RFB susceptibility among MDR-TB isolates in an HIV endemic region.…”

Section: Introductionmentioning

confidence: 99%

Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa

Rukasha

Said

Omar³

et al. 2016

Front. Microbiol.

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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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Molecular Detection of Rifabutin-Susceptible Mycobacterium tuberculosis

Cited by 16 publications

References 9 publications

Profiling of rpoB Mutations and MICs for Rifampin and Rifabutin in Mycobacterium tuberculosis

Profiling of rpoB Mutations and MICs for Rifampin and Rifabutin in Mycobacterium tuberculosis

Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex

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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