Delamanid, bedaquiline, and linezolid minimum inhibitory concentration distributions and resistance-related gene mutations in multidrug-resistant and extensively drug-resistant tuberculosis in Korea

Jeong Seong Yang, Kyung Jong Kim, Hongjo Choi, Seung Heon Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.

Original languageEnglish
Pages (from-to)563-568
Number of pages6
JournalAnnals of Laboratory Medicine
Volume38
Issue number6
DOIs
Publication statusPublished - 2018 Jan 1
Externally publishedYes

Fingerprint

Linezolid
bedaquiline
Extensively Drug-Resistant Tuberculosis
Microbial Sensitivity Tests
Korea
Genes
Mutation
Drug Resistance
Pharmaceutical Preparations
Tuberculosis
Mycobacterium tuberculosis
OPC-67683

Keywords

  • Bedaquiline
  • Delamanid
  • Linezolid
  • Minimum inhibitory concentration
  • Mutation
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

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title = "Delamanid, bedaquiline, and linezolid minimum inhibitory concentration distributions and resistance-related gene mutations in multidrug-resistant and extensively drug-resistant tuberculosis in Korea",
abstract = "Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.",
keywords = "Bedaquiline, Delamanid, Linezolid, Minimum inhibitory concentration, Mutation, Mycobacterium tuberculosis",
author = "Yang, {Jeong Seong} and Kim, {Kyung Jong} and Hongjo Choi and Lee, {Seung Heon}",
year = "2018",
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day = "1",
doi = "10.3343/alm.2018.38.6.563",
language = "English",
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journal = "Annals of Laboratory Medicine",
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publisher = "Seoul National University",
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TY - JOUR

T1 - Delamanid, bedaquiline, and linezolid minimum inhibitory concentration distributions and resistance-related gene mutations in multidrug-resistant and extensively drug-resistant tuberculosis in Korea

AU - Yang, Jeong Seong

AU - Kim, Kyung Jong

AU - Choi, Hongjo

AU - Lee, Seung Heon

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.

AB - Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.

KW - Bedaquiline

KW - Delamanid

KW - Linezolid

KW - Minimum inhibitory concentration

KW - Mutation

KW - Mycobacterium tuberculosis

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