Genome and MIC stability in Mycobacterium tuberculosis and indications for continuation of use of isoniazid in multidrug-resistant tuberculosis

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dc.contributor.authorVictor T.C.
dc.contributor.authorWarren R.
dc.contributor.authorButt J.L.
dc.contributor.authorJordaan A.M.
dc.contributor.authorFelix J.V.
dc.contributor.authorVenter A.
dc.contributor.authorSirgel F.A.
dc.contributor.authorSchaaf H.S.
dc.contributor.authorDonald P.R.
dc.contributor.authorRichardson M.
dc.contributor.authorCynamon M.H.
dc.contributor.authorVan Helden P.D.
dc.date.accessioned2011-05-15T16:17:02Z
dc.date.available2011-05-15T16:17:02Z
dc.date.issued1997
dc.description.abstractMycobacterium tuberculosis strains resistant to two or more of the first line antituberculosis drugs (MDR) are a serious threat to successful tuberculosis control programmes. For this retrospective study, 85 follow-up drug resistant isolates from 23 patients residing in a community with a high incidence of tuberculosis were collected and the level of in-vitro resistance to antibiotics determined quantitatively. PCR-SSCP and sequencing techniques were used to screen for gene mutations associated with resistance in 31 follow-up samples from a smaller group of eight patients. DNA fingerprint analysis was done on sequential isolates to confirm identity. Although treatment had a profound effect on changes in drug resistance patterns, the MIC for a particular agent remained constant in follow-up isolates. DNA fingerprinting and mutational analysis (14 different loci) showed that the genome of MDR strains of M. tuberculosis is relatively stable during the course of therapy. The rpoB gene was the most frequently mutated structural gene involved in drug resistance and a novel C to T mutation upstream of open reading frame (ORF)1. of the inhA operon was detected. No evidence was found of the presence of strain W (New York) in this group of MDR strains. The results stress the importance of confirming individuality of strains for the accurate calculation of frequencies of particular mutations associated with drug resistance, particularly in a high incidence area. Approximately one-half (47.8%) of the patients had isolates resistant to concentrations just above the critical concentration for isoniazid (MICs of 0.2-5 mg/L). Therefore, these patients and their contacts who develop primary drug-resistant tuberculosis may respond to higher dosages of treatment which could have a considerable impact on the cost and the ease of management of resistant tuberculosis.
dc.description.versionArticle
dc.identifier.citationJournal of Medical Microbiology
dc.identifier.citation46
dc.identifier.citation10
dc.identifier.issn00222615
dc.identifier.urihttp://hdl.handle.net/10019.1/14046
dc.subjectethambutol
dc.subjectisoniazid
dc.subjecttuberculostatic agent
dc.subjectarticle
dc.subjectcost
dc.subjectdna fingerprinting
dc.subjectdrug dose
dc.subjectgenome
dc.subjectmanagement
dc.subjectminimum inhibitory concentration
dc.subjectmultidrug resistance
dc.subjectmycobacterium tuberculosis
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjecttuberculosis
dc.subjectAntitubercular Agents
dc.subjectCatalase
dc.subjectDNA Fingerprinting
dc.subjectDrug Resistance, Microbial
dc.subjectDrug Resistance, Multiple
dc.subjectFollow-Up Studies
dc.subjectHumans
dc.subjectIsoniazid
dc.subjectMicrobial Sensitivity Tests
dc.subjectMycobacterium tuberculosis
dc.subjectPolymerase Chain Reaction
dc.subjectPolymorphism, Single-Stranded Conformational
dc.subjectRetrospective Studies
dc.subjectSequence Analysis, DNA
dc.subjectSouth Africa
dc.subjectTuberculosis, Pulmonary
dc.subjectVariation (Genetics)
dc.titleGenome and MIC stability in Mycobacterium tuberculosis and indications for continuation of use of isoniazid in multidrug-resistant tuberculosis
dc.typeArticle
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