Detection of
            <i>embB306</i>
            Mutations in Ethambutol-Susceptible Clinical Isolates of
            <i>Mycobacterium tuberculosis</i>
            from Northwestern Russia: Implications for Genotypic Resistance Testing

Mokrousov, Igor; Otten, Tatiana; Vyshnevskiy, Boris; Narvskaya, Olga

doi:10.1128/jcm.40.10.3810-3813.2002

Cited by 99 publications

(87 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…our own results on embB306 variation in Bulgarian population of M. tuberculosis (57) are in line with earlier findings (45,46) and German results (43) which correlated mutations in embB306 with eMB resistance. they are in contradiction with more recently reported discrepancies between genotypic and phenotypic eMB resistance (16,34, and references therein). A number of explanations of these contradictory findings have been proposed.…”

Section: Drug-resistance In Mycobacterium Tuberculosis: Molecular Bascontrasting

confidence: 54%

“…the prevalence of resistance to eMB, initial and acquired, is not generally high and varies in different countries from 1.3% in canada (47) to 23.3% in pakistan (22), with an overall average of 4-9% for initial resistance (67,68), and is predominant among patients with MDR TB. For the first time, Mokrousov et al (34) highlighted a presence of embB306 mutations in eMB-susceptible strains and hazbon et al (16) suggested an association of embB306 mutations with broad drug resistance and clustering rather than eMB resistance. our own results on embB306 variation in Bulgarian population of M. tuberculosis (57) are in line with earlier findings (45,46) and German results (43) which correlated mutations in embB306 with eMB resistance.…”

Section: Drug-resistance In Mycobacterium Tuberculosis: Molecular Basmentioning

confidence: 99%

See 1 more Smart Citation

Drug-Resistance inMycobacterium Tuberculosis:Molecular Basis and Genotypic Detection

Valcheva¹,

Mokrousov²

2011

Biotechnology & Biotechnological Equipment

Self Cite

View full text Add to dashboard Cite

Section: Drug-resistance In Mycobacterium Tuberculosis: Molecular Bascontrasting

confidence: 54%

Section: Drug-resistance In Mycobacterium Tuberculosis: Molecular Basmentioning

confidence: 99%

Drug-Resistance inMycobacterium Tuberculosis:Molecular Basis and Genotypic Detection

Valcheva¹,

Mokrousov²

2011

Biotechnology & Biotechnological Equipment

Self Cite

View full text Add to dashboard Cite

“…Thus, our study confirms previous investigations that describe a clear correlation between mutations in emb306 and EMB resistance, 11,21 without any indication of an influence on the resistance to other antituberculous drugs as suggested by other authors. 13,15,16 This high concordance between both assays was, however, determined only after repeating conventional drug susceptibility testing, pointing to problems with conventional diagnostics of EMB resistance. Indeed, due to the small difference between the critical concentration used for EMB drug susceptibility testing and the MIC, conventional drug susceptibility testing for EMB is less reliable, yields less reproducible results, and has a lower sensitivity when compared with other drugs.…”

Section: Resultsmentioning

confidence: 96%

“…9 However, if clinical isolates are considered, the percentage of EMB resistant strains which show mutations in embB306 ranges from 30 to 68%. 10,11 Additionally, a number of recent investigations described the occurrence of embB306 mutations in EMB susceptible strains, [12][13][14] and several studies reporting an association with broad drug resistance rather than with EMB resistance alone. 15,16 These contradictory results cast doubt on the potential use of embB306 mutations as molecular markers for predicting EMB resistance in clinical isolates.…”

Section: Introductionmentioning

confidence: 99%

Tuberculosis ethambutol resistance: Concordance between phenotypic and genotypic test results

Plinke

Cox

Kalon³

et al. 2009

Tuberculosis

View full text Add to dashboard Cite

s u m m a r y embB306 mutations are potential markers for detecting ethambutol resistance in clinical Mycobacterium tuberculosis isolates. However, more recently, embB306 mutations have been found in ethambutol susceptible isolates and an association with broad drug resistance rather than ethambutol resistance has been reported.To further investigate this question, we analyzed the association between embB306 mutations and phenotypic ethambutol resistance among 197 isolates from a drug resistance survey performed in Karakalpakstan, Uzbekistan.39 strains had an embB306 mutation, out of which seven were ethambutol susceptible, thus, displaying discrepant test results. After re-analysis, the seven isolates were tested ethambutol resistant. All of these strains had an increased ethambutol MIC, however, three strains showed no or weak growth on the critical concentration of 2 mg/ml on Lö wenstein-Jensen. In three strains we confirmed the presence of heteroresistant mixed populations which might influence conventional ethambutol testing. Final concordance between molecular and phenotypic EMB testing was high with a sensitivity of 78% and a specificity of 100%.Our results confirm that embB306 mutations are useful markers for predicting ethambutol resistance. Discrepancies between molecular and phenotypic ethambutol resistance test results are most likely caused by problems with conventional susceptibility testing.

show abstract

“…Associations between this genotype family and resistance to anti-TB drugs, including RIF, INH, and FQs, have been reported previously (9,10,25,(27)(28)(29)(30)43). In our study only two strains belonged to the T1 family strains, and both of them had the mutation D94N detected in the Beijing family strains as well.…”

Section: Discussionmentioning

confidence: 98%

Evaluation of Two Molecular Assays for Rapid Detection of Mycobacterium tuberculosis Resistance to Fluoroquinolones in High-Tuberculosis and -Multidrug-Resistance Settings

et al. 2011

View full text Add to dashboard Cite

The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of drug resistance, including multidrug and extensive drug resistance to TB (M/XDRTB). Rapid diagnosis of resistance to fluoroquinolones (FQs) using molecular assays is essential for the implementation of appropriate drug regimens and prevention of the transmission of XDR strains. A total of 51 individual MDRTB strains were tested by pyrosequencing of the quinolone resistance determining region of the gyrA gene and the GenoType MTBDRsl assay (Hain Lifescience, GmbH, Nehren, Germany), and the results were evaluated against those obtained by phenotypic drug susceptibility testing (DST). Mutations were detected in 25 (78.1%) FQ-resistant strains, with the majority of mutations (n ‫؍‬ 19 [73.0%]) found in codon 94 of the gyrA gene; the novel mutation 1457 C3⌻ was found in the gyrB gene. Three mixed allelic variants were detected, which is a well-known phenomenon in areas with high TB and drug-resistant TB rates. The sensitivity and specificity of pyrosequencing (86.2 and 100%, respectively) and MTBDRsl (86.2 and 100%, respectively) were high; however, the results for 5.9% of the analyzed strains were unreadable when MTBDRsl was used. The MTBDRsl and pyrosequencing assays offer a rapid and accurate means for diagnosing resistance to FQs in high-TB-burden areas.Tuberculosis (TB) remains a major threat to public health worldwide and in the developing world in particular, causing almost 2 million deaths annually. The real magnitude of drug resistance is not yet known, although the Indian subcontinent, China, and Russia are believed to account for the majority of cases globally (48).Multidrug-resistant TB (MDRTB), caused by TB bacilli resistant to both isoniazid (INH) and rifampin (RIF), poses difficulties in diagnosis and treatment, with lower survival rates (especially in HIV-infected persons) and the associated high costs of TB control programs. The World Health Organization (WHO) estimates current MDRTB rates in new and previously treated cases globally to be 2.9 and 15.3%, respectively (50).The Russian Federation is a high-TB-burden country with high rates of TB drug resistance, dominated by TB strains of the Beijing family reported to be associated with MDRTB (7, 42). The Samara Oblast (Central Russia) is a hot spot for both TB and HIV epidemics; ca. 20% of new TB cases are MDR, with rates even higher in previously treated cases and in the prison sector (8). Converging TB, drug-resistant TB, and HIV epidemics pose a serious problem for low-and middle-income countries such as Russia where access to second-and third-line drug therapy is limited (2, 8).The rate of extensively drug-resistant TB (XDRTB) (which is caused by MDRTB bacilli with additional resistance to a fluoroquinolone [FQ] and one or more injectable drugs) has been increasing in Russia (36) due to multiple incomplete treatment regimens and poor infection control practice. Cases of XDRTB show a high rate of treatment failure and mortality especially in XDRTB patients with c...

show abstract

Detection of embB306 Mutations in Ethambutol-Susceptible Clinical Isolates of Mycobacterium tuberculosis from Northwestern Russia: Implications for Genotypic Resistance Testing

Cited by 99 publications

References 19 publications

Drug-Resistance inMycobacterium Tuberculosis:Molecular Basis and Genotypic Detection

Drug-Resistance inMycobacterium Tuberculosis:Molecular Basis and Genotypic Detection

Tuberculosis ethambutol resistance: Concordance between phenotypic and genotypic test results

Evaluation of Two Molecular Assays for Rapid Detection of Mycobacterium tuberculosis Resistance to Fluoroquinolones in High-Tuberculosis and -Multidrug-Resistance Settings

Contact Info

Product

Resources

About