Extensively drug-resistant tuberculosis in Myanmar: burden and mutations causing second-line drug resistance

Int J Tuberc Lung Dis. 2018 Jan 1;22(1):47-53. doi: 10.5588/ijtld.17.0321.

Abstract

Setting: Two tuberculosis (TB) reference laboratories in Myanmar.

Objectives: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar.

Design: This was a cross-sectional, retrospective study. Multidrug-resistant Mycobacterium tuberculosis isolates were collected during 2015-2016. Phenotypic drug susceptibility testing (DST) was performed and drug-resistant mutations identified by sequencing. Genotypes were determined to explain relationships between drug resistance patterns and genotypes.

Results: Of 89 MDR-TB isolates, 12 were XDR-TB and 24 were pre-XDR-TB, with 21 resistant to fluoroquinolones (FQs) and 3 to second-line injectable agents (SLIDs). High rates of cross-resistance among second-line drugs were observed. Correlations between phenotypic and molecular DST against FQs and SLIDs were 91% in both cases. The most frequent mutation in FQ-resistant isolates was D94G (8/21) in gyrA and A1401G (11/15) in rrs in those resistant to SLIDs. The dominant genotype was the Beijing type (76/89).

Conclusion: There were high proportions of XDR-TB and pre-XDR-TB among MDR-TB cases; cross-resistance among second-line drugs was high, with various types of genetic mutations. These data suggest that resistance to second-line anti-tuberculosis drugs should be monitored intensively, and molecular DST should be employed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Cross-Sectional Studies
  • Drug Resistance, Multiple, Bacterial / genetics
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Extensively Drug-Resistant Tuberculosis / epidemiology
  • Extensively Drug-Resistant Tuberculosis / microbiology
  • Genotype
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Myanmar / epidemiology
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / isolation & purification
  • Retrospective Studies
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antitubercular Agents