Mutations in the rrs A1401G gene and phenotypic resistance to amikacin and capreomycin in mycobacterium tuberculosis
Date
2012
Authors
Sirgel F.A.
Tait M.
Warren R.M.
Streicher E.M.
Bottger E.C.
Van Helden P.D.
Gey Van Pittius N.C.
Coetzee G.
Hoosain E.Y.
Chabula-Nxiweni M.
Journal Title
Journal ISSN
Volume Title
Publisher
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 (>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.
Description
Keywords
agar, alanine, amikacin, bacterial DNA, bacterial protein, capreomycin, glycine, Middlebrook 7H11 agar, protein rrs, tlyA protein, unclassified drug, antibiotic resistance, antibiotic sensitivity, article, bacterial strain, bacterium isolate, clinical article, cohort analysis, controlled study, cross resistance, DNA sequence, drug bioavailability, extensively drug resistant tuberculosis, gene expression, gene mutation, human, minimum inhibitory concentration, multidrug resistant tuberculosis, Mycobacterium tuberculosis, nonhuman, phenotype, priority journal, South Africa, wild type
Citation
Microbial Drug Resistance
18
2
193
197
18
2
193
197