Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea.

Ei PW, et al. J Korean Med Sci. 2016 Nov;31(11):1673-1683. https://doi.org/10.3346/jkms.2016.31.11.1673

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) have been a serious threat to control TB.…

Background: Drug-resistant tuberculosis (TB), including resistance to both rifampicin (RIF) and isoniazid (INH) referred to as multidrug-resistant tuberculosis (MDR-TB), has become an increasing global threat in recent years. Effective management of patients infected with MDR-TB strains requires identifying such patients by performing conventional drug-susceptibility testing (DST) on bacteria isolated from sputum, a process that can take up to 2 months. This delay in diagnosis can result in worsening and continued transmission of MDR-TB. Molecular methods that rely upon nucleic acid amplification of specific alleles known to be associated with resistance to specific drugs have been helpful in shortening the time to detect drug resistant TB. Methods: We investigated the utility of the REBA MTB-Rifa®, a commercially available line probe assay (LPA) for detecting rifampicin (RIF) resistance in the RIF resistance-determining region (RRDR) of the rpoB gene. Altogether, 492 Mycobacterium tuberculosis (M. tuberculosis) clinical isolates and additional 228 smear- and culture-positive sputum samples with confirmed M. tuberculosis were collected from subjects with suspected MDR-TB in South Korea. The results were compared with conventional phenotypic DST and sequencing of the rpoB gene. Results: A total of 215 of the 492 isolates were resistant to RIF by conventional DST, and of which 92.1% (198/215) were MDR-TB strains. The REBA MTB-Rifa® assay identified RIF resistance in 98.1% (211/215) of these isolates but failed to identify resistance in four phenotypically RIF resistant isolates. These four isolates lacked mutations in the RRDR but three were confirmed to be MDR-TB strains by sequencing. The sensitivity and specificity of this test for clinical isolates was thus 98.1% (211/215) and 100% (277/277), respectively. When applied directly to 228 smear positive sputum samples, the sensitivity and the specificity of REBA MTB-Rifa® assay was 100% (96/96, 132/132), respectively. Conclusions: These findings support the use of the REBA MTB-Rifa® assay for rapid detection of RIF resistance on clinical isolates and smear positive sputum samples. The results also suggest that RIF resistance is a good surrogate marker of MDR-TB in South Korea and the need to add more probes to other LPAs which can cover newly identified mutations relevant to RIF 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 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.