scholarly journals High Level of Cross-Resistance between Kanamycin, Amikacin, and Capreomycin among Mycobacterium tuberculosis Isolates from Georgia and a Close Relation with Mutations in the rrs Gene

2009 ◽  
Vol 53 (12) ◽  
pp. 5064-5068 ◽  
Author(s):  
Levan Jugheli ◽  
Nino Bzekalava ◽  
Pim de Rijk ◽  
Krista Fissette ◽  
Françoise Portaels ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Close Relation ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Rrna Gene ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Strains ◽  
High Level

ABSTRACT The aminoglycosides kanamycin and amikacin and the macrocyclic peptide capreomycin are key drugs for the treatment of multidrug-resistant tuberculosis (MDR-TB). The increasing rates of resistance to these drugs and the possible cross-resistance between them are concerns for MDR-TB therapy. Mutations in the 16S rRNA gene (rrs) have been associated with resistance to each of the drugs, and mutations of the tlyA gene, which encodes a putative rRNA methyltransferase, are thought to confer capreomycin resistance in Mycobacterium tuberculosis bacteria. Studies of possible cross-resistance have shown variable results. In this study, the MICs of these drugs for 145 clinical isolates from Georgia and the sequences of the rrs and tlyA genes of the isolates were determined. Of 78 kanamycin-resistant strains, 9 (11.5%) were susceptible to amikacin and 16 (20.5%) were susceptible to capreomycin. Four strains were resistant to capreomycin but were susceptible to the other drugs, whereas all amikacin-resistant isolates were resistant to kanamycin. Sequencing revealed six types of mutations in the rrs gene (A514C, C517T, A1401G, C1402T, C1443G, T1521C) but no mutations in the tlyA gene. The A514C, C517T, C1443G, and T1521C mutations showed no association with resistance to any of the drugs. The A1401G and C1402T mutations were observed in 65 kanamycin-resistant isolates and the 4 capreomycin-resistant isolates, respectively, whereas none of the susceptible isolates showed either of those mutations. The four mutants with the C1402T mutations showed high levels of resistance to capreomycin but no resistance to kanamycin and amikacin. Detection of the A1401G mutation appeared to be 100% specific for the detection of resistance to kanamycin and amikacin, while the sensitivities reached 85.9% and 94.2%, respectively.

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 Multidrug-Resistant Tuberculosis in Alberta and British Columbia, 1989 to 1998

1999 ◽  
Vol 6 (2) ◽  
pp. 155-160 ◽  
Author(s):  
Ahmed Hersi ◽  
Kevin Elwood ◽  
Robert Cowie ◽  
Dennis Kunimoto ◽  
Richard Long
Keyword(s):  
British Columbia ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Foreign Born ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Culture Positive

OBJECTIVE: To describe the extent of the problem of multidrug-resistant tuberculosis (MDR-TB) in Alberta and British Columbia from 1989 to 1998.DESIGN: A retrospective, population-based descriptive study of all notified MDR-TB cases in the context of all notified TB cases, all notified culture-positive TB cases and all notified drug-resistant TB cases.SETTING: Provinces of Alberta and British Columbia, and their TB registries.PATIENTS: All people with TB reported to the TB registries of Alberta and British Columbia between January 1, 1989 and June 30, 1998.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive TB. Demographic, clinical and laboratory data on all cases of MDR-TB were recorded.RESULTS: Of 4606 notified cases of TB, 3553 (77.1%) were culture positive. Of these, 365 (10.3%) were drug resistant; of the drug-resistant cases, 24 (6.6%) were MDR. Most MDR-TB patients were foreign-born; of the four Canadian-born patients, two were infected while travelling abroad. Although foreign-born patients were significantly more likely to harbour drug-resistant strains, 14.3% versus 4.8%, respectively (P<0.001), among those who were harbouring a drug-resistant strain, the proportion of Canadian-born versus foreign-born patients with an MDR strain was the same (6.7% versus 6.6%, respectively). From 1994 to 1998 versus 1989 to 1993, the proportion of all drug-resistant strains that were MDR was greater (9.0% versus 4.3%, respectively), but the difference was not statistically significant. Isolates from 16 of the 24 MDR-TB cases had been archived. Each of these was fingerprinted and found to be unique. Most MDR-TB cases (88%) were respiratory. Of those tested for human immunodeficiency virus (n=17), only one was seropositive. MDR-TB was ‘acquired’ in 67% and ‘primary’ in 33% of cases. Eight (33%) of the MDR-TB cases received curative courses of treatment, six (25%) are still being treated, and the remainder have either died (five, 21%), transferred out (four, 17%) or become ‘chronic’ (one, 4%). No secondary case of MDR-TB has been identified in Alberta and British Columbia.CONCLUSIONS: Most MDR-TB in Alberta and British Columbia is imported. The proportion of all drug-resistant cases that are MDR appears to be increasing, but not because of disease acquired from recent contact with MDR-TB in Canada.

scholarly journals Genotypic diversity of multi- and pre-extremely drug-resistant Mycobacterium tuberculosis isolates from Morocco

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253826
Author(s):  
Amal Oudghiri ◽  
Ghizlane Momen ◽  
Achraf Aainouss ◽  
Amin Laglaoui ◽  
My Driss El Messaoudi ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Genotypic Diversity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Control Programs ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Database Clustering ◽  
High Level

In Morocco, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase especially within previously treated cases; these MDR cases may evolve to extensively drug resistant tuberculosis (XDR-TB) raising major concern to TB control programs. From an epidemiological window, scarce informations are available about the genetic diversity of Mycobacterium tuberculosis (MTB) strains fueling these forms of resistance. The aim of this study was to assess to genetic diversity of MDR-MTB strains. Hence, this prospective study was conducted on patients diagnosed with MDR-TB at Pasteur Institute of Casablanca from 2010 to 2013. A total of 70 MDR-MTB isolates were genotyped by spoligotyping and 15-loci MIRU-VNTR methods. Spoligotyping generated four orphan patterns, five unique profiles whereas 61 strains were grouped in nine clusters (2 to 25 strains per cluster), the clustering rates being 87.1%. Subtyping by 15 loci MIRU-VNTR splitted all clusters already established by spoligotyping and generated 70 unique profiles not recognized in SITVIT2 database; clustering rate was equal to zero. HGDI analysis of 15 loci MIRU demonstrated that eight out of 15 loci were highly discriminant. Of note, all pre-XDR strains belongs to many clades, meaning that there no association between gyrA mutants and particular clade. Overall, the data generated by this study (i) describe the population structure of MDR MTBC in Morocco which is highly homogenous, (ii) confirm that TB in Morocco is almost exclusively transmitted by modern and evolutionary lineages with high level of biodiversity seen by MIRU, and (iii) validate the use of optimized 15-loci MIRU-VNTR format for future investigations in Morocco.

Tuberculosis Multidrug-resistant Tuberculosis – From Epidemiology to Treatment Design

2015 ◽  
Vol 01 (01) ◽  
pp. 20
Author(s):  
Jean-Pierre Zellweger ◽  
Keyword(s):  
Multidrug Resistant ◽  
Rapid Identification ◽  
Drug Management ◽  
Duration Of Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Selection Of

Multidrug-resistant tuberculosis (MDR-TB) and extensively resistant tuberculosis (XDR-TB) are present in most regions of the world and represent a serious threat to the control of tuberculosis. They usually result from errors somewhere along the chain of management of the disease that favoured the selection of resistant mutants, progressively replacing drug-sensitive strains and transmitted to further patients. The currently recommended strategies for the control of this serious situation is the rapid identification of drug-resistant strains, careful drug management of patients with second-line drugs and prevention of the transmission of mycobacteria to contacts. Optimal selection and number of drugs and duration of treatment are not clearly defined. Prevention of the creation of additional cases of MDR-TB is crucial.

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 Primary Clofazimine and Bedaquiline Resistance among Isolates from Patients with Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Jian Xu ◽  
Bin Wang ◽  
Minghao Hu ◽  
Fengmin Huo ◽  
Shaochen Guo ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated ◽  
Alamarblue Assay

ABSTRACT Clofazimine has been repurposed for the treatment of tuberculosis, especially for multidrug-resistant tuberculosis (MDR-TB). To test the susceptibility to clofazimine of Mycobacterium tuberculosis clinical isolates, MICs of clofazimine were determined using the microplate alamarBlue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. For five clofazimine-resistant strains isolated from previously treated pre-extensively drug-resistant TB (pre-XDR-TB) and XDR-TB patients without prior exposure to clofazimine or bedaquiline, clofazimine MICs were ≥1.2 μg/ml. Four isolates with cross-resistance to bedaquiline had Rv0678 mutations. The other isolate with no resistance to bedaquiline had an Rv1979c mutation. This study adds to a recent study showing that 6.3% of MDR-TB patients without prior clofazimine or bedaquiline exposure harbored isolates with Rv0678 mutations, which raises concern that preexisting resistance to these drugs may be associated with prior TB treatment. Furthermore, we propose a tentative breakpoint of 1.2 μg/ml for clofazimine resistance using the MABA method. More-widespread surveillance and individualized testing for clofazimine and bedaquiline resistance, together with assessment of their clinical usage, especially among previously treated and MDR-TB patients, are warranted.

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 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.

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