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

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 drugresistant mutations identified by sequencing. Genotypes were determined to explain relationships between drug resistance patterns and genotypes. Rwsults: 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 XDRTB and pre-XDR-TB among MDR-TB cases; crossresistance 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.