Analysis of the genetic determinants of multidrug and extensive drug resistance in Mycobacterium tuberculosis with the use of an oligonucleotide microchip

ABSTRACTThe increasing incidence of extensively drug-resistant (XDR)Mycobacterium tuberculosisin high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDRM. tuberculosisstrains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the “hot-spot” regions ofrpoB,katG,inhA,ahpC,gyrA,gyrB, andrrsgenes in 50 XDRM. tuberculosisstrains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDRM. tuberculosisstrains would be undetected if only these common hot-spot regions were tested. The frequencies of resistance-conferring mutations were found to be comparable among all XDRM. tuberculosisstrain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDRM. tuberculosisstrains.

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Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis Beijing B0/W148 isolates

10.1183/13993003.congress-2019.pa3019 ◽

2019 ◽

Author(s):

Tatiana Umpeleva ◽

Kseniya Belousova ◽

Ludmila Golubeva ◽

Nataliya Eremeeva ◽

Diana Vakhrusheva

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Genetic Determinants

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Characterization of mutations in multi- and extensive drug resistance among strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2013.02.035 ◽

2013 ◽

Vol 76 (2) ◽

pp. 187-196 ◽

Cited By ~ 45

Author(s):

Hum Nath Jnawali ◽

Sung Chul Hwang ◽

Young Kil Park ◽

Hyejin Kim ◽

Yeong Seon Lee ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Clinical Isolates ◽

Republic Of Korea ◽

Extensive Drug Resistance

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Drugresistance of Mycobacterium tuberculosis from surgical material taken from patients with pulmonary tuberculosis

MedAlliance ◽

10.36422/23076348-2021-9-1-6-10 ◽

2021 ◽

Vol 9 (1) ◽

pp. 6-10

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Molecular Genetic ◽

Study Drug ◽

Newly Diagnosed ◽

Duration Of Treatment ◽

Nutrient Media ◽

Number Of Patients ◽

Extensive Drug Resistance ◽

Resis Tance

At present, with the improvement of epidemic indicators for tuberculosis, the number of patients with drug-resis- tant forms of tuberculosis is increasing, which compli- cates and increases the duration of treatment of suchpatients. The aim of the work is to study drug resistance of mycobacterium tuberculosis (MBT) obtained from sur- gical material. Methods. 74 patients with radical and di- agnostic operations on the chest organs were included into the study. All patients were examined by standard me thods: microscopy, molecular genetic methods, cul- turing on so lid and liquid nutrient media of sputum, and, in case of bronchoscopy, BALF. The diagnosis of tuber- culosis was confirmed morphologically in all patients by histological examination of the surgical material. When analyzing the results of DR MBT, it was found that among the newly diagnosed patients, more than half (59.3%) had multiple (44.6%; p<0.001) and extensive drug resistance (14.7%; p=0.003), while in 74.5% (n=35/47) before the op- eration MBT were not detected in sputum. The frequency of development of drug resistance to anti-tuberculosis drugs of the first and reserve lines, and the structure of drug resis tance depending on the group of dispensary registration are presented. Comparative analysis of MBT LS isolated from sputum before operations and from the operating material was conducted. The results of the study showed a high percentage of MBT drug resistance obtained in the operating material in patients with nega- tive MBT tests. More than half of patients who did not receive antibiotic therapy before surgery have MDR and XDR, which suggests a high regional primary drug resist- ance of Mycobacterium tuberculosis.

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IN VITRO ACTION OF THE DRUG CANDIDATE OF PBTZ169, HYDROCHLORIDE ACTION IN RESPECT OF CLINICAL STRAINS OF MYCOBACTERIUM TUBERCULOSIS WITH EXTENSIVE DRUG RESISTANCE

Tuberculosis and lung diseases ◽

10.21292/2075-1230-2016-94-9-73-79 ◽

2016 ◽

Vol 94 (9) ◽

pp. 73-79 ◽

Cited By ~ 1

Author(s):

L. N. Chernousova ◽

S. N. Andreevskaya ◽

T. G. Smirnova ◽

E. E. Larionova ◽

I. Yu. Andrievskaya ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Drug Candidate ◽

Clinical Strains ◽

Extensive Drug Resistance

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Tuberculosis outcomes related to the Mycobacterium tuberculosis genotype

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-2019-3-4-531-538 ◽

2019 ◽

Vol 9 (3-4) ◽

pp. 531-538

Author(s):

O. A. Pasechnik ◽

A. A. Vyazovaya ◽

M. A. Dymova ◽

A. I. Blokh ◽

V. L. Stasenko ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Drug Susceptibility ◽

Biological Properties ◽

Drug Susceptibility Testing ◽

Beijing Genotype ◽

Multi Drug Resistance ◽

Co Morbidity ◽

Extensive Drug Resistance ◽

Phylogenetic Lineages

Mycobacterium tuberculosis strains of different phylogenetic lineages and genetic families differ in biological properties that determine, to some extent, epidemiological features and clinical manifestation in tuberculosis (TB) patients.The aim of the study was to assess the risk of an adverse outcome of the disease in TB patients caused by various M. tuberculosis genotypes.Materials and methods. A total of 425 patients with respiratory TB were enrolled in this study. They were registered at phthisiatric facilities in the Omsk region from March 2015 to June 2017 period and included: males — 73.1%, mean age 39.9 years, females — 26.9%, mean age 42.0 years. M. tuberculosis culture and drug susceptibility testing and DNA extraction were performed in accordance with standard methods. Strains were assigned to the M. tuberculosis Beijing genotype and its epidemiologically relevant clusters B0/W148 and 94-32 by PCR based detection of specific markers. Non-Beijing strains were subjected to spoligotyping.Results. We found that 66.5% isolates belonged to the Beijing genotype, 12.8% — to LAM, 10.1% — to T, and 4.7% — to the Ural genotype. Multi-drug resistance (MDR) to anti-TB drugs was observed in 195 M. tuberculosis strains (45.9%). Moreover, Beijing genotype was more often isolated from patients with MDR-TB infection (PR = 2.09 (95% CI 1.6–2.74) and TB infection associated with HIV infection (PR = 1.14 (95% CI 1.01–1.31). Lethal outcome was double higher in patients infected with Beijing vs. non-Beijing strains, 28.6% vs. 14.0% (PR = 2.03; 95% CI 1.3–3.17). The risk factors were identified as follows: young age 18–44 years (RR = 1.7; 95% CI 1.18–2.7), co-morbidity with HIV (RR = 5.0; 95% CI 3.39–7.45), multiple (RR = 1.7; 95% CI 1.14–2.55) and extensive drug resistance (RR = 2.57; 95% CI 1.35–4.92), and association with the Beijing genotype (RR = 2.0, 95% CI 1.3–3.17).Conclusion. M. tuberculosis spread in the Omsk region is characterised by significant prevalence of the Beijing genotype, associated with multiple and extensive drug resistance. A significant association of adverse clinical outcomes and various factors, including association with the Beijing genotype, requires development of new approaches in the fight against tuberculosis.

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