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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

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dc.contributor.author Jugheli, L.
dc.contributor.author Bzekalava, N.
dc.contributor.author de Rijk, P.
dc.contributor.author Fissette, K.
dc.contributor.author Portaels, F.
dc.contributor.author Rigouts, L.
dc.date.accessioned 2009-12-21T13:33:19Z
dc.date.available 2009-12-21T13:33:19Z
dc.date.issued 2009
dc.identifier.issn 0066-4804
dc.identifier.doi http://dx.doi.org/10.1128/AAC.00851-09
dc.identifier.other ITG-M1B
dc.identifier.other ITG-M2B
dc.identifier.other ITG-M3B
dc.identifier.other ITG-M4B
dc.identifier.other ITG-M5A
dc.identifier.other ITG-MLA
dc.identifier.other MICRO
dc.identifier.other U-MYCOB
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other UPD17
dc.identifier.other ABSTRACT
dc.identifier.uri http://hdl.handle.net/10390/2860
dc.description.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. en
dc.language English en
dc.subject Bacterial diseases en
dc.subject Tuberculosis en
dc.subject Mycobacterium tuberculosis en
dc.subject Drug resistance en
dc.subject Cross-resistance en
dc.subject Kanamycin en
dc.subject Amikacin en
dc.subject Capreomycin en
dc.subject Mutations en
dc.subject 16S rRNA gene en
dc.subject Georgia en
dc.subject Asia, Central en
dc.title 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 en
dc.type Article en
dc.citation.issue 12 en
dc.citation.jtitle Antimicrobial Agents and Chemotherapy en
dc.citation.volume 53 en
dc.citation.pages 5064-5068 en
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/19752274
dc.citation.jabbreviation Antimicrob Agents Chemother en


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