The GenoType MTBDRsl test rapidly detects resistance to
ethambutol,
fluoroquinolones, and second-line
aminoglycosides (
amikacin and
kanamycin) and
cyclic peptide (
capreomycin) in Mycobacterium tuberculosis. A set of 41 multidrug-resistant (MDR) M.
tuberculosis strains, 8 extensively drug-resistant (XDR) M.
tuberculosis strains, and 3 non-MDR M.
tuberculosis strains were tested by the MTBDRsl test and by
DNA sequencing of the resistance-determining regions in gyrA and gyrB (
fluoroquinolones [FQ]), rpsL (
streptomycin), rrs and tlyA (
aminoglycosides and/or
cyclic peptide), and embB (
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 in gyrB 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 in rrs 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 in embB, 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 in gyrB) 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.