Mutations in the rrs A1401G gene and phenotypic resistance to amikacin and capreomycin in mycobacterium tuberculosis

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dc.contributor.authorSirgel F.A.
dc.contributor.authorTait M.
dc.contributor.authorWarren R.M.
dc.contributor.authorStreicher E.M.
dc.contributor.authorBottger E.C.
dc.contributor.authorVan Helden P.D.
dc.contributor.authorGey Van Pittius N.C.
dc.contributor.authorCoetzee G.
dc.contributor.authorHoosain E.Y.
dc.contributor.authorChabula-Nxiweni M.
dc.contributor.authorHayes C.
dc.contributor.authorVictor T.C.
dc.contributor.authorTrollip A.
dc.date.accessioned2012-05-17T08:58:56Z
dc.date.available2012-05-17T08:58:56Z
dc.date.issued2012
dc.description.abstractThe aminoglycosides amikacin (AMK)/kanamycin (KAN) and the cyclic polypeptide capreomycin (CAP) are important injectable drugs in the treatment of multidrug-resistant tuberculosis. Cross-resistance among these drug classes occurs and information on the minimum inhibitory concentrations (MICs), above the normal wild-type distribution, may be useful in identifying isolates that are still accessible to drug treatment. Isolates from the Eastern Cape Province of South Africa were subjected to DNA sequencing of the rrs (1400-1500 region) and tlyA genes. Sequencing data were compared with (i) conventional susceptibility testing at standard critical concentrations (CCs) on Middlebrook 7H11 agar and (ii) MGIT 960-based MIC determinations to assess the presence of AMK- and CAP-resistant mutants. Isolates with an rrs A1401G mutation showed high-level resistance to AMK (>20mg/L) and decreased phenotypic susceptibility to CAP (MICs 10-15mg/L). The MICs of CAP were below the bioavailability of the drug, which suggests that it may still be effective against multi- or extensively drug resistant tuberculosis [M(X)DR-TB]. Agar-based CC testing was found to be unreliable for resistance recognition of CAP in particular. © 2012 Mary Ann Liebert, Inc.
dc.identifier.citationMicrobial Drug Resistance
dc.identifier.citation18
dc.identifier.citation2
dc.identifier.citation193
dc.identifier.citation197
dc.identifier.issn10766294
dc.identifier.other10.1089/mdr.2011.0063
dc.identifier.urihttp://hdl.handle.net/10019.1/21033
dc.subjectagar
dc.subjectalanine
dc.subjectamikacin
dc.subjectbacterial DNA
dc.subjectbacterial protein
dc.subjectcapreomycin
dc.subjectglycine
dc.subjectMiddlebrook 7H11 agar
dc.subjectprotein rrs
dc.subjecttlyA protein
dc.subjectunclassified drug
dc.subjectantibiotic resistance
dc.subjectantibiotic sensitivity
dc.subjectarticle
dc.subjectbacterial strain
dc.subjectbacterium isolate
dc.subjectclinical article
dc.subjectcohort analysis
dc.subjectcontrolled study
dc.subjectcross resistance
dc.subjectDNA sequence
dc.subjectdrug bioavailability
dc.subjectextensively drug resistant tuberculosis
dc.subjectgene expression
dc.subjectgene mutation
dc.subjecthuman
dc.subjectminimum inhibitory concentration
dc.subjectmultidrug resistant tuberculosis
dc.subjectMycobacterium tuberculosis
dc.subjectnonhuman
dc.subjectphenotype
dc.subjectpriority journal
dc.subjectSouth Africa
dc.subjectwild type
dc.titleMutations in the rrs A1401G gene and phenotypic resistance to amikacin and capreomycin in mycobacterium tuberculosis
dc.typeArticle
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