Open AccessDetection by GenoType MTBDR sl Test of Complex Mechanisms of Resistance to Second-Line Drugs and Ethambutol in Multidrug-Resistant Mycobacterium tuberculosis Complex Isolates
Author(s) -
Florence Brossier,
Nicolas Véziris,
Alexandra Aubry,
Vincent Jarlier,
Wladimir Sougakoff
Publication year - 2010
Publication title -
journal of clinical microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.349
H-Index - 255
eISSN - 1070-633X
pISSN - 0095-1137
DOI - 10.1128/jcm.01947-09
Subject(s) - ethambutol , capreomycin , amikacin , kanamycin , mycobacterium tuberculosis , microbiology and biotechnology , biology , streptomycin , virology , tuberculosis , medicine , antibiotics , pathology
The GenoType MTBDRsl test rapidly detects resistance to ethambutol, fluoroquinolones, and second-line aminoglycosides (amikacin and kanamycin) and cyclic peptide (capreomycin) inMycobacterium tuberculosis . A set of 41 multidrug-resistant (MDR)M. tuberculosis strains, 8 extensively drug-resistant (XDR)M. tuberculosis strains, and 3 non-MDRM. tuberculosis strains were tested by the MTBDRsl test and by DNA sequencing of the resistance-determining regions ingyrA andgyrB (fluoroquinolones [FQ]),rpsL (streptomycin),rrs andtlyA (aminoglycosides and/or cyclic peptide), andembB (ethambutol). The sensitivity and specificity of the MTBDRsl test were as follows: 87% and 96%, respectively, for fluoroquinolones; 100% for both for amikacin; 77% and 100%, respectively, for kanamycin, 80% and 98%, respectively, for capreomycin; and 57% and 92%, respectively, for ethambutol. Analysis of the discrepant results indicated that three FQ-resistant strains (including one XDR strain) with mutations ingyrB were missed by the MTBDRsl test and that one FQ-susceptible strain, identified as resistant by the MTBDRsl test, had a double mutation (T80A-A90G) in GyrA that did not confer resistance to FQ. Five strains (including two XDR strains) without mutations inrrs were monoresistant to aminoglycosides or cyclic peptide and were missed by the MTBDRsl test. Finally, 12/28 ethambutol-resistant strains had no mutation at codon 306 inembB , while 2/24 ethambutol-susceptible strains had such a mutation. In conclusion, the MTBDRsl test efficiently detects the most common mutations involved in resistance to fluoroquinolones, aminoglycosides/cyclic peptide, and ethambutol and accurately assesses susceptibility to amikacin. However, due to mutations not included in the test (particularly ingyrB ) or resistance mechanisms not yet characterized (particularly those related to ethambutol resistance and to monoresistance to aminoglycosides or cyclic peptide), the wild-type results yielded by the MTBDRsl test should be confirmed by drug susceptibility testing.