Multidrug-resistant tuberculosis in Taiwan

In a population-based study, 297 cases of MDR-TB accounted for 1.0% of the 30,193 TB cases reported from 2019 to 2022. Among these, 219 (73.7%) were male, and 78 (26.3%) were female, with a median age of 63 years (ranging from 50 to 76 years). Of the cases, 242 (81.5%) were new, 52 (17.5%) were previously treated, and 3 (1.0%) had an unknown treatment history.[1]

A maximum-likelihood phylogenetic tree was constructed based on 3,453 SNPs in the non-repetitive regions of the studied isolates, which included 45 (15.2%) pre-XDR and 6 (2.0%) XDR-TB cases. Lineage 2 isolates were predominant, comprising 43 (14.5%) sublineage 2.1 (proto-Beijing) and 145 (48.8%) sublineage 2.2 (modern Beijing) isolates. Using a 12-SNP cut-off, 25.3% (75/297) of MDR-TB cases were grouped into 20 clusters, with cluster sizes ranging from 2 to 13 cases.[1]

Univariate analysis revealed a correlation between MDR-TB clusters and male sex. Individuals carrying the sublineage 2.1 proto-Beijing genotype had a higher risk of transmitting the infection. We identified putative compensatory mutations in the rpoA, rpoC, or non-RRDR regions of the rpoB genes in 161 (54.2%) MDR isolates. The most predominant mutation was rpoC V483G (17/161, 10.6%), followed by rpoC A172V (14/161, 8.7%) and rpoC E750D (14/161, 8.7%).[1]

The putative compensatory mutation rpoC E750D was not previously reported and was found exclusively among sublineage 2.1 isolates. Additionally, 43.4% (129/297) of M. tuberculosis isolates harbored concurrent compensatory mutations with the rpoB S450L mutation. Notably, these mutations were significantly associated with clustering. Specifically, rpoC E750D in sublineage 2.1 and rpoC D485Y/rpoC E1140D in sublineage 2.2 were associated with MDR-TB transmission.[1] 

Another study examined the impact of new and repurposed anti-TB drugs on treatment outcomes in fluoroquinolone (FQ)-resistant multidrug-resistant tuberculosis (MDR-TB) patients. Among 109 FQ-resistant and 218 FQ-susceptible MDR-TB patients treated at the Taiwan MDR-TB Consortium (TMTC) between 2009 and 2019, FQ-resistant cases showed higher resistance to other TB drugs and were more common in females (p < 0.01). The use of new or repurposed drugs, particularly clofazimine, was more frequent in FQ-resistant MDR-TB (55.1%) than in FQ-susceptible cases (28.9%) (p < 0.01). Notably, patients treated with at least two such drugs had no treatment failure, significantly improving outcomes in FQ-resistant cases (p = 0.03).[2]

Despite these benefits, FQ-resistant MDR-TB patients had lower treatment success (71.6%) compared to FQ-susceptible patients (85.8%) (p < 0.01), and treatment failure was observed only in the FQ-resistant group (8.3%). Mortality was higher in FQ-resistant cases (19.3% vs. 13.8%), though most deaths were unrelated to TB. Multivariable analysis identified older age (≥65 years) and comorbidities as major predictors of poor outcomes. While the use of at least two new or repurposed drugs eliminated treatment failure in FQ-resistant MDR-TB, further research is needed to explore shorter treatment regimens for improving outcomes.[2]

References:

1. Liu, K.H., Xiao, Y.X. and Jou, R., 2024. Multidrug-resistant tuberculosis clusters and transmission in Taiwan: a population-based cohort study. Frontiers in Microbiology, 15, p.1439532. 

2. Huang, Y.W., Yu, M.C., Lin, C.B., Lee, J.J., Lin, C.J., Chien, S.T., Lee, C.H. and Chiang, C.Y., 2024. Mitigating treatment failure of pulmonary pre-extensively drug-resistant tuberculosis: The role of new and repurposed drugs. Journal of Microbiology, Immunology and Infection, 57(4), pp.617-628.