scholarly journals Mutation and Transmission Profiles of Second-Line Drug Resistance in Clinical Isolates of Drug-Resistant Mycobacterium tuberculosis From Hebei Province, China

2019 ◽  
Vol 10 ◽  
Author(s):  
Qianlin Li ◽  
Huixia Gao ◽  
Zhi Zhang ◽  
Yueyang Tian ◽  
Tengfei Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hebei Province ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Second Line ◽  
Line Drug

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

2014 ◽  
Vol 59 (1) ◽  
pp. 414-420 ◽  
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.

scholarly journals Detection of First- and Second-Line Drug Resistance in Mycobacterium tuberculosis Clinical Isolates by Pyrosequencing

2012 ◽  
Vol 50 (6) ◽  
pp. 2026-2033 ◽  
Author(s):  
Anna Engström ◽  
Nora Morcillo ◽  
Belen Imperiale ◽  
Sven E. Hoffner ◽  
Pontus Juréen
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Clinical Isolates ◽  
Second Line ◽  
Line Drug

scholarly journals Detection of Second Line Drug Resistance among Drug Resistant Mycobacterium Tuberculosis Isolates in Botswana

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 208 ◽  
Author(s):  
Tuelo Mogashoa ◽  
Pinkie Melamu ◽  
Brigitta Derendinger ◽  
Serej D. Ley ◽  
Elizabeth M. Streicher ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility Testing ◽  
World Health ◽  
Fluoroquinolone Resistance ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Second Line ◽  
Mdr Tb ◽  
Line Drug

The emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis (M.tb) strains is a threat to global tuberculosis (TB) control. The early detection of drug resistance is critical for patient management. The aim of this study was to determine the proportion of isolates with additional second-line resistance among rifampicin and isoniazid resistant and MDR-TB isolates. A total of 66 M.tb isolates received at the National Tuberculosis Reference Laboratory between March 2012 and October 2013 with resistance to isoniazid, rifampicin or both were analyzed in this study. The genotypes of the M.tb isolates were determined by spoligotyping and second-line drug susceptibility testing was done using the Hain Genotype MTBDRsl line probe assay version 2.0. The treatment outcomes were defined according to the Botswana national and World Health Organization (WHO) guidelines. Of the 57 isolates analyzed, 33 (58%) were MDR-TB, 4 (7%) were additionally resistant to flouroquinolones and 3 (5%) were resistant to both fluoroquinolones and second-line injectable drugs. The most common fluoroquinolone resistance-conferring mutation detected was gyrA A90V. All XDR-TB cases remained smear or culture positive throughout the treatment. Our study findings indicate the importance of monitoring drug resistant TB cases to ensure rapid detection of second-line drug resistance.

scholarly journals Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil

2020 ◽  
Vol 115 ◽  
Author(s):  
Tania Matsui ◽  
Juliana Maíra Watanabe Pinhata ◽  
Michelle Christiane da Silva Rabello ◽  
Angela Pires Brandão ◽  
Lucilaine Ferrazoli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Sao Paulo ◽  
Clinical Isolates ◽  
São Paulo ◽  
Second Line ◽  
Line Drug

scholarly journals Prevalence and Genetic Characterization of Second-Line Drug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in Rural China

2013 ◽  
Vol 57 (8) ◽  
pp. 3857-3863 ◽  
Author(s):  
Yi Hu ◽  
Sven Hoffner ◽  
Linlin Wu ◽  
Qi Zhao ◽  
Weili Jiang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Dna Sequences ◽  
Rural China ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Second Line ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Line Drug

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.

scholarly journals Evaluation of the GenoType MTBDR sl Version 2.0 Assay for Second-Line Drug Resistance Detection of Mycobacterium tuberculosis Isolates in South Africa

2016 ◽  
Vol 55 (3) ◽  
pp. 791-800 ◽  
Author(s):  
Y. Gardee ◽  
A. W. Dreyer ◽  
H. J. Koornhof ◽  
S. V. Omar ◽  
P. da Silva ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Sensitivity And Specificity ◽  
Drug Susceptibility Testing ◽  
Rapid Screening ◽  
Second Line ◽  
Content Type ◽  
Version 2.0 ◽  
Line Drug

ABSTRACT Early detection of resistance to second-line antituberculosis drugs is important for the management of multidrug-resistant tuberculosis (MDR-TB). The GenoType MTBDR sl version 2.0 (VER 2.0) line probe assay has been redesigned for molecular detection of resistance-conferring mutations of fluoroquinolones (FLQ) ( gyrA and gyrB genes) and second-line injectable drugs (SLID) ( rrs and eis genes). The study evaluated the diagnostic performance of the GenoType MTBDR sl VER 2.0 assay for the detection of second-line drug resistance compared with phenotypic drug susceptibility testing (DST), using the Bactec MGIT 960 system on Mycobacterium tuberculosis complex isolates from South Africa. A total of 268 repository isolates collected between 2012 and 2014, which were rifampin monoresistant or MDR based on DST, were selected. MTBDR sl VER 2.0 testing was performed on these isolates and the results analyzed. The MTBDR sl VER 2.0 sensitivity and specificity indices for culture isolates were the following: FLQ, 100% (95% confidence interval [CI] 95.8 to 100%) and 98.9% (95% CI, 96.1 to 99.9%); SLID, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.7 to 99.7%). The sensitivity and specificity observed for individual SLID were the following: amikacin, 93.8% (95% CI, 79.2 to 99.2%) and 98.5% (95% CI, 95.5 to 99.7%); kanamycin, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.5 to 99.7%); and capreomycin, 86.2% (95% CI, 68.3 to 96.1%) and 95.9% (95% CI, 92.2 to 98.2%). An interoperator reproducibility of 100% and an overall interlaboratory performance of 93% to 96% were found. The overall improvement in sensitivity and specificity with excellent reproducibility makes the GenoType MTBDR sl VER 2.0 a highly suitable tool for rapid screening of clinical isolates for second-line drug resistance for use in high-burden TB/HIV settings.

scholarly journals Phenylethyl Butyrate Enhances the Potency of Second-Line Drugs against Clinical Isolates of Mycobacterium tuberculosis

2011 ◽  
Vol 56 (2) ◽  
pp. 1142-1145 ◽  
Author(s):  
Thomas Grau ◽  
Petra Selchow ◽  
Marcel Tigges ◽  
Reto Burri ◽  
Marc Gitzinger ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Isolates ◽  
Second Line ◽  
Inhibitory Effects ◽  
Content Type ◽  
Growth Inhibitory ◽  
Promoter Mutations ◽  
Line Drug

ABSTRACTEthionamide (ETH) is a second-line drug for the treatment of tuberculosis. As a prodrug, ETH has to be activated by EthA.ethAis controlled by its repressor EthR. 2-Phenylethyl-butyrate (2-PEB) inhibits EthR binding, enhances expression of EthA, and thereby enhances the growth-inhibitory effects of ethionamide, isoxyl, and thiacetazone inMycobacterium tuberculosisstrains with resistance to ETH due toinhApromoter mutations but notethAmutations.

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