Drug-resistant strains of Mycobacterium tuberculosis isolated in Russia

SETTING: State Research Center for Applied Microbiology, Russian Research Institute of Pathisiopulmonology (Ministry of Health, Moscow). OBJECTIVE: To analyze drug-resistant clinical isolates of Mycobacterium tuberculosis obtained from patients referred to the institute from different parts of Russia, and to study the mechanisms of their rifampicin resistance. DESIGN: Fifty clinical isolates of M. tuberculosis were analysed. Polymerase chain reaction (PCR) and sequencing were used to study the mechanisms of rifampicin resistance in 25 isolates. RESULTS: Among cultures isolated from 50 patients, drug resistance was detected in 33. Most of the isolates were resistant to rifampicin (25 isolates), isoniazid (14 isolates), and streptomycin (seven isolates). Only 6% of the isolates were resistant to one drug, while 14% were resistant to two, 32% to three, 40% to four, and 8% to five drugs. Susceptible isolates were derived from 17 patients. The following point mutations and deletions in the rpoB locus, responsible for high level rifampicin resistance (more than 50 mu g/ml in egg-based medium), were detected: G-->A/335 (Arg-->Gln), C-->T/232 (His-->Tyr), C-->T/221 (Ser-->Leu), G-->T/202 (Asp-->Tyr), GA-->TT/202-203 (Asp-->Phe), Delta ATGGACCAG/199-207 (Met, Asp, Gin), A-->T/91 (met-->Leu), TG-->CC/227-228 (Leu-->Ser), GAG-->AGT/349-350-351(Gln-->Ser), Delta CCG/354(Gly). CONCLUSION: A number of previously unrecognised genetic modifications in the rpoB region were found in rifampicin-resistant strains isolated from patients from different parts of Russia.