Genetic Characterization of Second-Line Drug-Resistant and Extensively Drug-Resistant 
						Mycobacterium tuberculosis from the Northern Region of India

ABSTRACTThis study aimed to investigate the prevalence of resistance to second-line antituberculosis (anti-TB) drugs and its association with resistance-related mutations inMycobacterium tuberculosisisolated 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-resistantM. tuberculosisisolates, 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 ingyrA(29.1%) and A1401G inrrs(30.8%). Meanwhile, all 4 XDR-TB isolates had a mutation ingyrA, and 3 of them carried the A1401G mutation inrrs. Mutations ingyrAandrrswere 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.

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Characterization of the Genetic Diversity of Extensively-Drug Resistant Mycobacterium tuberculosis Clinical Isolates from Pulmonary Tuberculosis Patients in Peru

PLoS ONE ◽

10.1371/journal.pone.0112789 ◽

2014 ◽

Vol 9 (12) ◽

pp. e112789 ◽

Cited By ~ 13

Author(s):

Omar Cáceres ◽

Nalin Rastogi ◽

Carlos Bartra ◽

David Couvin ◽

Marco Galarza ◽

...

Keyword(s):

Genetic Diversity ◽

Mycobacterium Tuberculosis ◽

Pulmonary Tuberculosis ◽

Clinical Isolates ◽

Drug Resistant ◽

Tuberculosis Patients ◽

Extensively Drug Resistant

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Evaluation of Pyrosequencing for Detecting Extensively Drug-Resistant Mycobacterium tuberculosis among Clinical Isolates from Four High-Burden Countries

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03614-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 414-420 ◽

Cited By ~ 20

Author(s):

Kanchan Ajbani ◽

Shou-Yean Grace Lin ◽

Camilla Rodrigues ◽

Duylinh Nguyen ◽

Francine Arroyo ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

The Philippines ◽

Drug Susceptibility Testing ◽

Clinical Isolates ◽

Drug Resistant ◽

Second Line ◽

Additional Advantage ◽

Content Type ◽

Extensively Drug Resistant

ABSTRACTReliable molecular diagnostics, which detect specific mutations associated with drug resistance, are promising technologies for the rapid identification and monitoring of drug resistance inMycobacterium tuberculosisisolates. Pyrosequencing (PSQ) has the ability to detect mutations associated with first- and second-line anti-tuberculosis (TB) drugs, with the additional advantage of being rapidly adaptable for the identification of new mutations. The aim of this project was to evaluate the performance of PSQ in predicting phenotypic drug resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) clinical isolates from India, South Africa, Moldova, and the Philippines. A total of 187 archived isolates were run through a PSQ assay in order to identifyM. tuberculosis(via the IS6110marker), and to detect mutations associated with M/XDR-TB within small stretches of nucleotides in selected loci. The molecular targets includedkatG, theinhApromoter and theahpC-oxyRintergenic region for isoniazid (INH) resistance; therpoBcore region for rifampin (RIF) resistance;gyrAfor fluoroquinolone (FQ) resistance; andrrsfor amikacin (AMK), capreomycin (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing results for performance analysis. The PSQ assay illustrated good sensitivity for the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool that reveals specific nucleotide changes associated with resistance to the first- and second-line anti-TB drug medications. This methodology has the potential to be linked to mutation-specific clinical interpretation algorithms for rapid treatment decisions.

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