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


Sirgel, F A; Tait, M; Warren, R M; Streicher, E M; Böttger, E C; Van Helden, P D; Gey Van Pittius, N C; Coetzee, G; Hoosain, E Y; Chabula-Nxiweni, M; Hayes, C; Victor, T C; Trollip, A (2012). Mutations in the rrs A1401G gene and phenotypic resistance to amikacin and capreomycin in mycobacterium tuberculosis. Microbial Drug Resistance, 18(2):193-197.

Abstract

The 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 (>20 mg/L) and decreased phenotypic susceptibility to CAP (MICs 10-15 mg/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.

Abstract

The 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 (>20 mg/L) and decreased phenotypic susceptibility to CAP (MICs 10-15 mg/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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:2012
Deposited On:14 Sep 2011 10:24
Last Modified:07 Dec 2017 08:58
Publisher:Mary Ann Liebert
ISSN:1076-6294
Additional Information:This is a copy of an article published in the Microbial Drug Resistance © 2011 copyright Mary Ann Liebert, Inc.; Microbial Drug Resistance is available online at: http://www.liebertonline.com
Publisher DOI:https://doi.org/10.1089/mdr.2011.0063
PubMed ID:21732736

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