title: Prevalence and genetic characterization of second-line drug-resistant and extensively drug-resistant Mycobacterium tuberculosis in Rural China.
abstract: This study aimed to investigate the prevalence of resistance to second-line antituberculosis (anti-TB) drugs and its association with resistance-related mutations in Mycobacterium tuberculosis isolated in China. In the present study, we collected 380 isolates from a population-based study in China and tested the drug susceptibility to first- and selected second-line drugs. These results were compared with polymorphisms in the DNA sequences of genes associated with drug resistance and MIC values of the studied second-line drugs. Of 43 multidrug-resistant M. tuberculosis isolates, 13 showed resistance to fluoroquinolones or injectable second-line drugs (preextensively drug-resistant TB [pre-XDR-TB]), and 4 were resistant to both and thus defined as extensively drug-resistant TB (XDR-TB). Age and previous TB therapy, including use of second-line drugs, were two independent factors associated with increased resistance to both first- and second-line drugs. Molecular analysis identified the most frequent mutations in the resistance-associated genes: D94G in gyrA (29.1%) and A1401G in rrs (30.8%). Meanwhile, all 4 XDR-TB isolates had a mutation in gyrA, and 3 of them carried the A1401G mutation in rrs. Mutations in gyrA and rrs were associated with high-level resistance to fluoroquinolones and the second-line injectable drugs. In addition to the identification of resistance-associated mutations and development of a rapid molecular test to diagnose the second-line drug resistance, it should be a priority to strictly regulate the administration of second-line drugs to maintain their efficacy to treat multidrug-resistant TB.
authors.affiliation: Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffner
authors.forename: Linlin
authors.initials: L
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Weili
authors.initials: W
authors.lastname: Jiang
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology; D002207:Capreomycin / Q000494:pharmacology; D002681:China / Q000453:epidemiology; D003430:Cross-Sectional Studies; D027081:DNA Gyrase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D024841:Fluoroquinolones; D005798:Genes, Bacterial; D006801:Humans; D007612:Kanamycin / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015995:Prevalence; D012424:Rural Population; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D002207:Capreomycin; D007612:Kanamycin; D000583:Amikacin; D027081:DNA Gyrase