• Association between genotype and drug resistance profiles of Mycobacterium tuberculosis strains circulating in China in a national drug resistance survey.

      Zhou, Yang; van den Hof, Susan; Wang, Shengfen; Pang, Yu; Zhao, Bing; Xia, Hui; Anthony, Richard; Ou, Xichao; Li, Qiang; Zheng, Yang; et al. (2017)
      We describe the population structure of a representative collection of 3,133 Mycobacterium tuberculosis isolates, collected within the framework of a national resistance survey from 2007 in China. Genotyping data indicate that the epidemic strains in China can be divided into seven major complexes, of which 92% belonged to the East Asian (mainly Beijing strains) or the Euro-American lineage. The epidemic Beijing strains in China are closely related to the Beijing B0/W148 strain earlier described in Russia and a large cluster of these strains has spread national wide. The density of Beijing strains is high in the whole of China (average 70%), but the highest prevalence was found North of the Yellow river. The Euro-American lineage consists of three sublineages (sublineage_1, 2, and 3) and is more prevalent in the South. Beijing lineage showed the highest cluster rate of 48% and a significantly higher level of resistance to rifampicin (14%, p<0.001), ethambutol (9%, p = 0.001), and ofloxacin (5%, p = 0.011). Within the Euro-American Lineage, sublineage_3 revealed the highest cluster rate (28%) and presented a significantly elevated level of resistance to streptomycin (44%, p<0.001). Our findings suggest that standardised treatment in this region may have contributed to the successful spread of certain strains: sublineage_3 in the Euro-American lineage may have thrived when streptomycin was used without rifampicin for treatment, while later under DOTS based treatment, in which rifampicin plays a key role, Beijing lineage appears to be spreading.
    • Strong Increase in Moxifloxacin Resistance Rate among Multidrug-Resistant Mycobacterium tuberculosis Isolates in China, 2007 to 2013.

      Xia, Hui; Zheng, Yang; Liu, Dongxin; Wang, Shengfen; He, WenCong; Zhao, Bing; Song, Yuanyuan; Ou, Xichao; Zhou, Yang; van den Hof, Susan; et al. (2021-12-01)
      We designed this study to determine the trend of moxifloxacin resistance among multidrug-resistant tuberculosis (MDR-TB) patients from 2007 to 2013 in China to inform the composition of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment regimens. We assessed moxifloxacin resistance among MDR-TB isolates collected in national drug resistance surveys in 2007 and 2013 that included 3,634 smear-positive and 7,206 culture-positive pulmonary tuberculosis patients, respectively. Moxifloxacin susceptibility was examined by a Mycobacterium growth indicator tube (MGIT) 960 for the 2007 isolates, and by the minimum inhibitory concentration (MIC) method for the 2013 isolates, at both breakpoints 0.5 and 2.0 μg/mL. Risk factors were explored through multivariable log-binominal regression analysis. Mutations in gyrA and gyrB for part of the isolates were also studied through sequencing. Of 401 MDR strains isolated in 2007, moxifiloxacin resistance could be determined for 319 (79.6%): 41 (12.9%) and 10 (3.1%) were resistant at 0.5 and 2.0 μg/mL, respectively. Of 365 MDR strains isolated in 2013, 338 (92.6%) could be analyzed: 140 (41.4%) and 79 (23.4%) were resistant at 0.5 and 2.0 μg/mL. For patients in 2007, no characteristics were significantly associated with moxifloxacin resistance. For patients in 2013, patients aged ≥60 years (adjusted prevalence ratio [aPR], 1.46; 95% confidence interval [CI], 1.10 to 1.93) were more likely to have resistance at 0.5 μg/mL, whereas those residing in eastern China compared to those in central China had an increased risk of resistance at both 0.5 (aPR, 1.85; 95% CI, 1.38 to 2.48) and 2.0 μg/mL (aPR, 2.14; 95% CI, 1.35 to 3.40). Sequencing results were obtained for 245 and 266 MDR-TB isolates in 2007 and 2013, respectively. In total, 34 of 38 (89.5%) and 89 of 104 (85.6%) of 2007 and 2013 moxifloxacin-resistant (0.5 μg/mL) MDR-TB strains had mutations in the gyrA and gyrB gene, respectively. Asp94Gly was the most common mutation among 2007 (11 of 38, 28.9%) and 2013 isolates (24 of 104, 23.1%) and conferred high-level moxifloxacin resistance. Moxifloxacin resistance among MDR-TB patients in China increased from modest to high from 2007 to 2013. Moxifloxacin should be used carefully as a potentially effective drug for composing MDR/RR-TB regimens especially for elderly patients in China. Individual susceptibility testing especially rapid molecular-based assays should be conducted to confirm the susceptibility to moxifloxacin. IMPORTANCE China is one of the high-burden countries for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Moxifloxacin is one of the critical antituberculosis drugs for MDR/RR-TB treatment. Susceptibility to moxifloxacin is therefore very important to compose effective regimens and to provide protection against development of resistance of companion drugs such as bedaquiline and linezolid. There are, however, no nationally representative data on moxifloxacin resistance among MDR/RR-TB cases in China. Therefore, we assessed the resistance prevalence for moxifloxacin among MDR-TB strains isolated in national drug resistance surveys in 2007 and 2013 that covered 72 sites around the country. We demonstrate that the prevalence of moxifloxacin resistance in MDR-TB isolates increased from modest to high, which should prompt the national tuberculosis program to use moxifloxacin cautiously in second-line regimens to treat MDR/RR-TB unless susceptibility can be laboratory-confirmed.
    • Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China.

      Xia, Hui; van den Hof, Susan; Cobelens, Frank; Zhou, Yang; Zhao, Bing; Wang, Shengfen; Zhao, Yanlin (2020-01-07)