Sequence analyses of just four genes to detect extensively drug resistant tuberculosis among MDR-TB patients undergoing treatment. - Related Articles
Sequence analyses of just four genes to detect extensively drug resistant tuberculosis among MDR-TB patients undergoing treatment.
Antimicrob Agents Chemother. 2009 May 26;
Authors: Feuerriegel S, Cox HS, Zarkua N, Karimovich HA, Braker K, Rüsch-Gerdes S, Niemann S
Rapid detection of second line drug resistant tuberculosis is crucial to institute appropriate treatment regimens as early as possible. Although molecular methods have been successfully used for the rapid diagnosis of resistance to first-line drugs, there is limited data on mutations conferring resistance to second line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n=26) and to capreomycin and/or amikacin (n=48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs and tlyA). Ofloxacin (n=49) and capreomycin and/or amikacin (n=39) susceptible strains were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26) of the ofloxacin resistant strains, while none of the susceptible strains displayed mutations. The most common mutation occurs in gyrA codon 94 (17/26, 65.4%), followed by codons 90 and 91. Two strains showed mutations in gyrB at codons 485 and 543; both have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40, 85.0%). Three strains had mutations in tlyA, of which two (codon 18, 118) were associated with resistance to capreomycin alone. Overall, 10 resistant strains (five amikacin resistant and capreomycin susceptible), and all 39 susceptible control strains had no mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions in relatively few target genes to rapidly detect second line drug resistance in strains isolated from patients undergoing MDR-TB treatment. The mechanisms conferring amikacin resistance in this setting remain unclear.
PMID: 19470506 [PubMed - as supplied by publisher] [Tuberculosis Pulmonary]