scholarly journals Determination of MIC Distribution and Epidemiological Cutoff Values for Bedaquiline and Delamanid in Mycobacterium tuberculosis Using the MGIT 960 System Equipped with TB eXiST

2015 ◽  
Vol 59 (7) ◽  
pp. 4352-4355 ◽  
Author(s):  
Peter M. Keller ◽  
Rico Hömke ◽  
Claudia Ritter ◽  
Giorgia Valsesia ◽  
Guido V. Bloemberg ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Wild Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Type Strains

ABSTRACTBedaquiline (Sirturo) and delamanid (Deltyba) have recently been approved by the regulatory authorities for treatment of multidrug-resistant tuberculosis (MDR-TB). Antimicrobial susceptibility testing is not established for either substance. On the basis of the use of the MGIT 960 system equipped with EpiCenter/TB eXiST, we determined a mean bedaquiline MIC for wild-type strains of 0.65 mg/liter (median, 0.4 mg/liter) and an epidemiological cutoff (ECOFF) of 1.6 mg/liter; for delamanid, a mean wild-type drug MIC of 0.013 mg/liter (median, 0.01 mg/liter) and an ECOFF of 0.04 mg/liter were determined.

scholarly journals Use of Genotype MTBDRplus Assay for Diagnosis of Multidrug-Resistant Tuberculosis in Nepal

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Elina Maharjan ◽  
Narayan Dutt Pant ◽  
Sanjeev Neupane ◽  
Jyoti Amatya ◽  
Bhawana Shrestha
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Conventional Drug ◽  
Mdr Tb ◽  
Genotype Mtbdrplus

The main aims of this study were to study the patterns of mutations in rpoB, katG, and inhA genes in Mycobacterium tuberculosis strains isolated from patients from Nepal and to evaluate the performance of genotype MTBDRplus assay, taking conventional drug susceptibility testing as gold standard for diagnosis of MDR-TB. A total of 69 Mycobacterium tuberculosis strains isolated from 73 smear positive sputum samples from patients suspected of suffering from multidrug-resistant tuberculosis were used in our study. The drug susceptibility pattern of Mycobacterium tuberculosis isolated from these sputum specimens was determined by using genotype MTBDRplus assay taking conventional drug susceptibility testing as reference. The sensitivity and specificity of the genotype MTBDRplus assay for the detection of MDR-TB were found to be 88.7% and 100%, respectively. 88.7% of the rifampicin resistant isolates had mutations in rpoB gene. Similarly, 79.7% and 9.4% of isoniazid resistant isolates had mutations in katG and inhA genes, respectively. Genotype MTBDRplus assay was found to be very rapid and highly sensitive and specific method for diagnosis of MDR-TB and will be very helpful for early diagnosis of MDR-TB in high tuberculosis burden countries.

scholarly journals Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolated in Nepal

2012 ◽  
Vol 56 (6) ◽  
pp. 2831-2836 ◽  
Author(s):  
Ajay Poudel ◽  
Chie Nakajima ◽  
Yukari Fukushima ◽  
Haruka Suzuki ◽  
Basu Dev Pandey ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Promoter Region ◽  
Multidrug Resistant ◽  
Content Type ◽  
Molecular Tests ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Substitution Mutations ◽  
Drug Resistant Strains

ABSTRACTDespite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. To develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance inMycobacterium tuberculosisis required. In the present study, we investigated the prevalence of mutations inrpoBandkatGgenes and theinhApromoter region in 158M. tuberculosisisolates (109 phenotypically MDR and 49 non-MDR isolates collected in Nepal) by DNA sequencing. Mutations affecting the 81-bp rifampin (RIF) resistance-determining region (RRDR) ofrpoBwere identified in 106 of 109 (97.3%) RIF-resistant isolates. Codons 531, 526, and 516 were the most commonly affected, at percentages of 58.7, 15.6, and 15.6%, respectively. Of 113 isoniazid (INH)-resistant isolates, 99 (87.6%) had mutations in thekatGgene, with Ser315Thr being the most prevalent (81.4%) substitution. Mutations in theinhApromoter region were detected in 14 (12.4%) INH-resistant isolates. The results from this study provide an overview of the current situation of RIF and INH resistance inM. tuberculosisin Nepal and can serve as a basis for developing or improving rapid molecular tests to monitor drug-resistant strains in this country.

scholarly journals Draft Genome Sequences of Two Drug-Resistant Mycobacterium tuberculosis Isolates from Myanmar

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Htin Lin Aung ◽  
Thanda Tun ◽  
Elizabeth Permina ◽  
Wint Wint Nyunt ◽  
Si Thu Aung ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Health Concerns ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) and lately, extensively drug-resistant TB (XDR-TB) are increasing global health concerns. Here, we present the genome sequences of two MDR-TB isolates from Myanmar, one of 27 countries with a high MDR-TB burden, and describe a number of mutations consistent with these being XDR-TB isolates.

scholarly journals Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDRsl Assays

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Adebisi Ajileye ◽  
Nataly Alvarez ◽  
Matthias Merker ◽  
Timothy M. Walker ◽  
Suriya Akter ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Specific Resistance ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Wild Type ◽  
Resistance Mutations ◽  
Content Type ◽  
Synonymous Mutations ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

ABSTRACT In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

A Case of Healthcare-Associated, Multidrug-Resistant Tuberculosis in Austria: Reconsidering the Value of Cohorting of Patients with Culture-Positive Tuberculosis

2007 ◽  
Vol 28 (4) ◽  
pp. 483-485
Author(s):  
Alexander Indra ◽  
Barbara Robl ◽  
Ingrid Aumüller ◽  
Eva Magnet ◽  
Stefan Meusburger ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Healthcare Associated ◽  
Culture Positive

Cohorting of patients with culture-positive tuberculosis is still widely practiced in Austria, a country where approximately 1% ofMycobacterium tuberculosisisolates are multidrug resistant. Cohorting of patients with tuberculosis prior to determination of drug susceptibility is unacceptable becauseM. tuberculosissuperinfection can occur.

scholarly journals Scrofula Caused by Multidrug-Resistant Tuberculosis

2020 ◽  
Author(s):  
Bárbara Pedro ◽  
Liliana Alves ◽  
Rita Magano ◽  
Tomás Nunes ◽  
Nuno Marques
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
Causes Of Death ◽  
Cervical Lymphadenopathy ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Immunodeficiency Virus ◽  
Mdr Tb ◽  
Hiv Negative

Tuberculosis (TB) is one of the top 10 causes of death worldwide. Multidrug-resistant tuberculosis (MDR-TB) occurs when at the minimum there is resistance to isoniazid and rifampin. Prevention of new infections of Mycobacterium tuberculosis and progression to TB disease is critical to reduce the burden and mortality of this disease. We present the case of a 73-year-old human immunodeficiency virus (HIV)-negative female who presented with cervical lymphadenopathy and who was diagnosed with MDR-TB.

scholarly journals Sequence Analysis of Fluoroquinolone Resistance-Associated GenesgyrAandgyrBin Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

2016 ◽  
Vol 54 (9) ◽  
pp. 2298-2305 ◽  
Author(s):  
Ritu Singhal ◽  
Paul R. Reynolds ◽  
Jamie L. Marola ◽  
L. Elaine Epperson ◽  
Jyoti Arora ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Indian Subcontinent ◽  
Amino Acid Position ◽  
Multidrug Resistant ◽  
High Rate ◽  
Fluoroquinolone Resistance ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in thegyrAandgyrBgenes ofMycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in thegyrAandgyrBgenes of acid-fast bacillus (AFB) smear-positive sediments or ofM. tuberculosisisolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of thegyrAandgyrBgenes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in thegyrAgenes of 25 strains, while no mutations were observed in thegyrBgenes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. ThegyrAmutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis.

scholarly journals Prevalence of Multidrug Resistance Mycobacterium Tuberculosis (MDR-TB) Using GeneXpert Assay in Northern Sudan, How Serious is the Situation?

2021 ◽  
Author(s):  
Sufian Khalid Noor ◽  
Mohamed Osman Elamin ◽  
Ziryab Imad Mahmoud ◽  
Mohammed Salah ◽  
Taqwa Anwar ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
World Health ◽  
River Nile ◽  
Cross Sectional ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
History Of ◽  
Health Organization

Background: World Health Organization (WHO) estimates that there were 558000 new cases with resistance to Rifampicin, of which 82% had multidrug-resistant tuberculosis (MDR-TB). Objectives: We aimed to identify the prevalence of MDR-TB in River Nile state, Sudan, and the risk factors contributing to its occurrence. Methods: This was a descriptive cross-sectional hospital-based study involved 200 specimens taken from patients suspected of having MDR-TB tested using an automated GeneXpert assay. Results: Results of GeneXpert assay showed that the presence of Mycobacterium tuberculosis in 81 (40.5%), and out of 81 positive test results there were 13 (16%) had MDR-TB. Additionally, 7 cases of MDR-TB were previously treated which represented about (53%) of MDR patients, the remaining 6 MDR-TB patients were new cases and represented (47%) of MDR-TB patients. Moreover, there were 4 MDR-TB patients who had a history of contact with MDR-TB patients. Conclusion: Prevalence of MDR-TB in River Nile State, Sudan was 16%, which is greater than WHO estimation for Sudan (10.1%). The results revealed that the main risk factor to develop MDR-TB was a history of contact with MDR-TB, so adherence to treatment and social awareness about the spread of MDR-TB are crucial preventive measures.

scholarly journals Mycobacterium tuberculosis Mutations Associated with Reduced Susceptibility to Linezolid

2016 ◽  
Vol 60 (4) ◽  
pp. 2542-2544 ◽  
Author(s):  
Shuo Zhang ◽  
Jiazhen Chen ◽  
Peng Cui ◽  
Wanliang Shi ◽  
Xiaohong Shi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rapid Detection ◽  
Multidrug Resistant ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTLinezolid (LZD) has become increasingly important for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its mechanisms of resistance are not well characterized. We isolated 32 mutants ofMycobacterium tuberculosiswith reduced susceptibility to LZD, which was accounted for byrrlandrplCmutations in almost equal proportions, causing lower and higher MICs, respectively. Our findings provide useful information for the rapid detection of LZD resistance for improved treatment of MDR-TB.

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