scholarly journals Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolates from China

2014 ◽  
Vol 58 (4) ◽  
pp. 1997-2005 ◽  
Author(s):  
Li-Li Zhao ◽  
Yan Chen ◽  
Hai-Can Liu ◽  
Qiang Xia ◽  
Xiao-Cui Wu ◽  
...  

ABSTRACTTo investigate the molecular characterization of multidrug-resistant tuberculosis (MDR-TB) isolates from China and the association of specific mutations conferring drug resistance with strains of different genotypes, we performed spoligotyping and sequenced nine loci (katG,inhA, theoxyR-ahpCintergenic region,rpoB,tlyA,eis,rrs,gyrA, andgyrB) for 128 MDR-TB isolates. Our results showed that 108 isolates (84.4%) were Beijing family strains, 64 (59.3%) of which were identified as modern Beijing strains. Compared with the phenotypic data, the sensitivity and specificity of DNA sequencing were 89.1% and 100.0%, respectively, for isoniazid (INH) resistance, 93.8% and 100.0% for rifampin (RIF) resistance, 60.0% and 99.4% for capreomycin (CAP) resistance, 84.6% and 99.4% for kanamycin (KAN) resistance, and 90.0% and 100.0% for ofloxacin (OFX) resistance. The most prevalent mutations among the MDR-TB isolates werekatG315,inhA15,rpoB531, -526, and -516,rrs1401,eis-10, andgyrA94, -90, and -91. Furthermore, there was no association between specific resistance-conferring mutations and the strain genotype. These findings will be helpful for the establishment of rapid molecular diagnostic methods to be implemented in China.

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Y. Hu ◽  
L. Xu ◽  
Y. L. He ◽  
Y. Pang ◽  
N. Lu ◽  
...  

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.


2016 ◽  
Vol 60 (9) ◽  
pp. 5159-5166 ◽  
Author(s):  
Dange Li ◽  
Yi Hu ◽  
Jim Werngren ◽  
Mikael Mansjö ◽  
Xubin Zheng ◽  
...  

ABSTRACTThe aim of this study was to investigate the epidemiology of pyrazinamide (PZA) resistance and the associated risk factors as well as to evaluate thepncAgene loci as a marker for PZA resistance in China. A population-based multicenter study of pulmonary tuberculosis (TB) cases was carried out from 2011 to 2013 in four Chinese districts/counties with different geographic and socioeconomic features. Testing for multidrug-resistant tuberculosis (MDR-TB) and susceptibility to PZA was done by the proportion method on Lowenstein-Jensen medium and Bactec MGIT 960, respectively. Mutations in thepncAgene were identified by sequencing. Among 878 culture-positive cases, 147 (16.7%) were resistant to PZA, with a significantly higher proportion among MDR isolates than among the first-line drug-susceptible isolates (30.2% versus 7.7%;P< 0.001). In total, 136 isolates had a nonsynonymouspncAmutation, with a comparable diagnostic performance between Beijing family and non-Beijing family as well as between MDR-TB and first-line drug-susceptible TB. Furthermore, the mutations in isolates with high-level PZA resistance (MIC > 500 mg/liter) were observed mainly in three regions of thepncAgene (codons 51 to 76, codons 130 to 142, and codons 163 to 180). Patients with prior treatment history had a significantly higher risk for PZA monoresistance (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.363 to 6.015) and MDR PZA resistance (OR, 6.47; 95% CI, 3.186 to 13.15), while the additional factors associated with MDR PZA resistance were the patient's age (OR, 1.02; 95% CI, 1.003 to 1.042), lung cavity (OR, 2.64; 95% CI, 1.296 to 5.391). These findings suggest that it is a priority to identify PZA resistance in MDR-TB and that a rapid molecular diagnostic test based onpncAmutations in the Chinese settings where MDR-TB prevalence is high should be developed.


2008 ◽  
Vol 52 (8) ◽  
pp. 2937-2939 ◽  
Author(s):  
Igor Mokrousov ◽  
Tatiana Otten ◽  
Olga Manicheva ◽  
Yulia Potapova ◽  
Boris Vishnevsky ◽  
...  

ABSTRACT In this work, we studied the variation in the gyrA and gyrB genes in ofloxacin- and multidrug-resistant Mycobacterium tuberculosis strains circulating in northwest Russia. Comparison with spoligotyping data suggested that similar to the spread of multidrug-resistant tuberculosis, the spread of fluoroquinolone-resistant tuberculosis in Russia may be due, at least partly, to the prevalence of the Beijing genotype in a local population of M. tuberculosis.


2018 ◽  
Vol 08 (02) ◽  
pp. 190-207
Author(s):  
Sureshbabu Jayachandra ◽  
Madhuresh Kumar Sethi ◽  
Vipin Kumar Kaushik ◽  
Vijayakrishna Ravi ◽  
Saiprasad Kottolla ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1169
Author(s):  
Precious Bwalya ◽  
Tomoyuki Yamaguchi ◽  
Eddie Samuneti Solo ◽  
Joseph Yamweka Chizimu ◽  
Grace Mbulo ◽  
...  

Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in rpsL, rrs, and gidB accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in rpsL was strongly associated with the CAS1_Kili genotype (p < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.


2021 ◽  
Vol 30 (3) ◽  
pp. 143-151
Author(s):  
Noha S. Soliman ◽  
Sahar M. Khairat ◽  
Mohamed Abdullah ◽  
Yasmin Adel El-Mahdy

Background: Multidrug-resistant tuberculosis (MDR-TB) and infections by nontuberculous mycobacteria (NTM) are diseases of major public health concern. Objective: The aim of the present work is to study the prevalence and patterns of MDRTB as well as the characterization of isolated NTM species. Methodology: All samples (1069) were subjected to smear microscopy, culture on Lowenstein-Jensen (LJ) media, and phenotypic drug susceptibility testing (DST) of MTB to isoniazid (INH), rifampin (RF), streptomycin (S), and ethambutol (E). GeneXpert was used for direct detection of MTB and RF resistance. Matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry (MS) was utilized for characterizing isolated NTM species. Results: M.tuberculosis (MTB) was isolated at a rate of 95.3% (1019/1069). MDR-TB was detected at rate of 7.16% with significant patterns for INH + RF + S + E (46.5%) and INR + RF (24.6%) (P-value <0.001). RF resistance was detected at a rate of 27.2% by GeneXpert. Seven NTM species (0.6%) were isolated in culture of which M.porcinum and M.fortuitum had confident identification by MALDI-TOF (score ≥1.8). Conclusion: MDR-TB rate was found to be 7.16% with significant dominance for INH + RF + S + E and INR + RF resistance patterns, while NTM rate was 0.6%.


2021 ◽  
pp. 28-35
Author(s):  
Petro V. Kuzyk ◽  
Andriy Yu. Horoshchak ◽  
Bogdan Ya. Serbin ◽  
Rahaina Musa-Bador ◽  
Uchenna Uchie-Okoro

TB is the seventh leading cause of death worldwide and third leading cause of death among women in the 15–44 age group1. However, in 2010, the number of multidrug-resistant tuberculosis (MDR-TB) cases rose to 650,000 worldwide, with more than 150,000 deaths. All of the well-known widely available methods such as chest X-ray, culture in liquid and solid media should be accompanied with the modern and more accurate methods such as chest CT and molecular diagnostic tests which proved the necessity of usage with high sensitivity and accuracy, especially in smear-negative pulmonary TB patients and patients with the multi drug resistant forms.


2015 ◽  
Vol 59 (4) ◽  
pp. 2045-2050 ◽  
Author(s):  
Li-li Zhao ◽  
Qing Sun ◽  
Hai-can Liu ◽  
Xiao-cui Wu ◽  
Tong-yang Xiao ◽  
...  

ABSTRACTEthambutol (EMB) plays a pivotal role in the chemotherapy of drug-resistant tuberculosis (TB), including multidrug-resistant tuberculosis (MDR-TB). Resistance to EMB is considered to be caused by mutations in theembCABoperon (embC,embA, andembB). In this study, we analyzed theembCABmutations among 139 MDR-TB isolates from China and found a possible association betweenembCABoperon mutation and EMB resistance. Our data indicate that 56.8% of MDR-TB isolates are resistant to EMB, and 82.2% of EMB-resistant isolates belong to the Beijing family. Overall, 110 (79.1%) MDR-TB isolates had at least one mutation in theembCABoperon. The majority of mutations were present in theembBgene and theembAupstream region, which also displayed significant correlations with EMB resistance. The most common mutations occurred at codon 306 inembB(embB306), followed byembB406,embA(−16), andembB497. Mutations atembB306 were associated with EMB resistance. DNA sequencing ofembB306–497 was the best strategy for detecting EMB resistance, with 89.9% sensitivity, 58.3% specificity, and 76.3% accuracy. Additionally,embB306 had limited value as a candidate predictor for EMB resistance among MDR-TB infections in China.


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