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    Feb 24, 2021
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    Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment

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    Authors
    Feuerriegel, S
    Cox, H S
    Zarkua, N
    Karimovich, H A
    Braker, K
    Rüsch-Gerdes, S
    Niemann, S
    Affiliation
    Research Center Borstel, National Reference Center for Mycobacteria, Parkallee 18, 23845 Borstel, Germany; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia; Medecins Sans Frontieres, Tashkent, Uzbekistan; Ministry of Health, Nukus, Karakalpakstan, Uzbekistan; Medecins Sans Frontieres, Berlin, Germany
    Issue Date
    2009-05-26
    
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    Journal
    Antimicrobial Agents and Chemotherapy
    Abstract
    The rapid detection of Mycobacterium tuberculosis isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n = 26) and to capreomycin and/or amikacin (n = 48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs, and tlyA). Strains susceptible to ofloxacin (n = 49) and capreomycin and/or amikacin (n = 39) were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in gyrA at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in gyrB, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40 strains [85.0%]). Three strains had mutations in tlyA, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.
    URI
    http://hdl.handle.net/10144/114155
    DOI
    10.1128/AAC.00050-09
    PubMed ID
    19470506
    Additional Links
    http://aac.asm.org/cgi/content/full/53/8/3353?view=long&pmid=19470506
    Type
    Article
    Language
    en
    ISSN
    1098-6596
    ae974a485f413a2113503eed53cd6c53
    10.1128/AAC.00050-09
    Scopus Count
    Collections
    TB

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