Increasing Prevalence of Rifampicin-Resistant Mycobacterium tuberculosis is Associated with the Transmission of Strains Harboring Compensatory Mutations in China: A 10-year Comparative Analysis [PublishAheadOfPrint]

In this report, we conducted bacterial population profile studies to assess trends of rifampicin (RIF) resistance from 2005 to 2015 of Mycobacterium tuberculosis (MTB) isolates collected across China. A total of randomly selected 273 and 269 MTB isolates from 2005 and 2015, respectively, were analyzed. The rates of RIF resistance (36.4%), isoniazid resistance (39.0%), and levofloxacin resistance (25.7%) in 2015 were significantly higher than in 2005 (28.2%, 30.0%, and 15.4%, respectively; P < 0.05). Genotypic data revealed 256 (95.2%) Beijing-type isolates in 2015, a rate significantly higher than that of 2005 (86.4%) (P < 0.01). A higher proportion of mutations were identified within the rifampin resistance determining region (RRDR) of rpoB in isolates from 2015 (99.0%) than in 2005 isolates (85.7%, P < 0.01). In addition, a significantly higher proportion of RIF-resistant isolates carrying compensatory mutations were observed in 2015 (31.6%) than in 2005 (7.8%). Notably, the great majority of these compensatory mutations (91.9%) were observed in isolates that harbored a mutation of codon 531 of the rpoB gene. In conclusion, our data demonstrate that resistance to RIF, isoniazid, and levofloxacin has become significantly more prevalent during the past decade. In addition, the prevalence of the Beijing genotype significantly increased from 2005 to 2015. Notably, a significantly increased frequency of strains with mutations in rpoC or rpoA is observed in those that have codon 531 mutations suggests that they may be compensatory, and may play a role in facilitating transmission.

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