Genotypicdiversity of drug-resistant isolates from Hebei, China.

Drug-resistant tuberculosis (DR-TB), particularly multidrug-resistant tuberculosis (MDR-TB), has been identified as a major challenge for effective TB control. For rapid detection and proper treatment, molecular assays based on the identification of mutations in genes associated with drug resistance have been established to determine drug resistance. However, there is as yet little information about drug resistance-associated mutations of clinical isolates from Hebei. In this study, four genetic loci , , intergenic region and were sequenced among 276 DR-TB isolates from Hebei to understand the association between specific mutations, drug resistance phenotypes and spoligotyping genotypes. Altogether, 83.8% of INH resistant isolates harbored at least one mutation of , , and intergenic region and 78.4% of RIF resistant isolates harbored one or more mutations in . The predominant mutation patterns of and in Hebei was Ser531Leu and Ser315Thr, respectively. Additionally, 91.2% of MDR isolates harbored at least one mutation in these four targeted fragments. Compared with the phenotypic data, the sensitivity and specificity of co-testing of , promoter and intergenic region for INH resistance were 83.8% and 96.8%, respectively and the exhibited a sensitivity of 78.4% and a specificity of 95.3% for RIF resistance. Furthermore, there was no association between drug resistance-conferring mutations and spoligotypes. This finding will be useful for the establishment of rapid molecular diagnostic methods in Hebei province, China.