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Rifampicin drug resistance tests for tuberculosis: challenging the gold standard

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dc.contributor.author Van Deun, A. en_US
dc.contributor.author Maug, A. K. en_US
dc.contributor.author Bola, V. en_US
dc.contributor.author Lebeke, R. en_US
dc.contributor.author Hossain, M. A. en_US
dc.contributor.author de Rijk, W. B. en_US
dc.contributor.author Rigouts, L. en_US
dc.contributor.author Gumusboga, M. en_US
dc.contributor.author Torrea, G. en_US
dc.contributor.author de Jong, B. C. en_US
dc.date.accessioned 2014-09-25T13:39:35Z
dc.date.available 2014-09-25T13:39:35Z
dc.date.issued 2013 en_US
dc.identifier.issn 0095-1137 en_US
dc.identifier.doi http://dx.doi.org/10.1128/JCM.00553-13 en_US
dc.identifier.other ITG-B1A; ITG-B5B; ITG-B6A; ITG-B7B; ITG-B8B; ITG-BLA; DBM; U-MYCOB; JIF; DOI; Abstract; UPD56 en_US
dc.identifier.uri http://hdl.handle.net/10390/7742
dc.description.abstract Setting:The rapid diagnosis of rifampicin resistance is hampered by reported insufficient specificity of molecular techniques for detection of rpoB mutations. Objective:To document the prevalence and prognostic value of rpoB mutations with unclear phenotypic resistance.Design:Sequencing directly from sputum of first failure or relapse patients without phenotypic selection; comparison of standard re-treatment regimen outcome by mutation. Results:Among all rpoB mutations, the best documented "disputed" rifampicin resistance mutations (511Pro, 516Tyr, 526Asn, 526Leu, 533Pro and 572Phe), made up 13.1% and 10.6% in Bangladesh and Kinshasa respectively. Except for the 511Pro and 526Asn mutations, most of these strains with disputed mutations tested rifampicin resistant in routine LJ proportion DST (78.7%), but significantly less than those with common, undisputed mutations (96.3%). With 63% of patients experiencing failure or relapse in both groups, there was no difference in outcome of first-line retreatment between patients carrying a strain with disputed versus common mutations. Conclusions:Rifampicin resistance that is difficult to detect by the gold standard, phenotypic DST, is clinically and epidemiologically highly relevant. Sensitivity rather than specificity is imperfect with any rifampicin DST method. Even at low prevalence, a rifampicin resistant result issued by a competent laboratory may not warrant confirmation, although this needs to be confirmed also for molecular results among new cases. However, a susceptible result should be questioned when suspicion is very high, and further DST using a different system (i.e. geno- after phenotypic) would be fully justified. en_US
dc.language English en_US
dc.subject Bacterial diseases en_US
dc.subject Tuberculosis en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject Drug resistance en_US
dc.subject Rifampicin en_US
dc.subject Drug susceptibility en_US
dc.subject Test en_US
dc.subject Phenotyping en_US
dc.subject Mutations en_US
dc.subject Gold standard en_US
dc.subject Laboratory techniques and procedures en_US
dc.title Rifampicin drug resistance tests for tuberculosis: challenging the gold standard en_US
dc.type Article en_US
dc.citation.issue 8 en_US
dc.citation.jtitle Journal of Clinical Microbiology en_US
dc.citation.volume 51 en_US
dc.citation.pages 2633-2640 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/23761144 en_US
dc.citation.jabbreviation J Clin Microbiol en_US


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