Detection by genotype MTBDRsl test of complex resistance mechanisms to second-line drugs and ethambutol in multidrug-resistant strains of Mycobacterium tuberculosis
Abstract number: O237
Brossier F., Veziris N., Aubry A., Jarlier V., Sougakoff W.
Objectives: The Genotype MTBDRsl test aims at rapid detection of resistance to ethambutol, fluoroquinolones and second line aminoglycosides (amikacin, kanamycin) and cyclic peptide (capreomycin) in Mycobacterium tuberculosis (Mtb).
Methods: A set of 41 MDR (multidrug-resistant) and 8 XDR (extensively drug-resistant) Mtb strains has been tested by MTBDRsl and DNA sequencing of the resistance-determining regions in gyrA and gyrB (fluoroquinolones), rpsl (streptomycin), rrs and tlyA (aminoglycosides-cyclic peptide) and embB (ethambutol).
Results: The values of sensitivity/specificity of the MTBDRsl test were as follows: fluoroquinolones 87/96%, amikacin 100/100%, kanamycin 77/100%, capreomycin 80/98% and ethambutol 57/92%. Analysis of the discrepant results indicated that 3 FQ-resistant strains (including one XDR) with mutations in gyrB were missed by MTBDRsl, and that one FQ-susceptible strain, identified as resistant by MTBDRsl, had a double mutation T80A-A90G in GyrA not conferring resistance to FQ. Five strains (including 2 XDR) without mutation in rrs were mono-resistant to aminoglycosides or cyclic peptide and were missed by MTBDRsl. Finally, 16/28 ethambutol-resistant strains had a mutation at codon 306 in embB while 2/24 ethambutol susceptible strains had such a mutation.
Conclusions: MTBDRsl 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 yet-uncharacterized resistance mechanisms (particularly those related to ethambutol and to aminoglycosides-cyclic peptide mono-resistance), the wild-type results yielded by the MTBDRsl test need to be confirmed by drug susceptibility testing when the prevalence of resistance is high.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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