Keywords
Abstract
The growth of multiple (MDR) and extensively drug resistance (XDR) of the tuberculosis causative agent continues on the background of epidemiological tension decrease. The question about change of the Mtb resistance level to isoniazid (H) is needed in reply. The frequency of the Mtb resistance to the H high concentrations (10 µg/ml) has been compared in the 3 periods: 1st - 2004-2006 (period near to the peak incidence of tuberculosis in Russia), 2nd - 2007-2011 (interim period), 3rd - 2012-2017 (period of stable decline in incidence). We have examined 942 poly-drug-resistant (PDR), MDR and XDR Mtb strains isolated from patients with pulmonary tuberculosis during these periods. Minimal inhibitory concentration (MIC) of H against 41 Mtb strains was tested by REMA. This H-resistant strains were isolated in 2014-2017. The proportion of strains resistant to H 10 ?g/ml has been decreased slightly from 1st period to the third: 27.1% - 24.3% - 18.6%. Inside each of the periods significant differences in the frequency of isolates resistant to H 10 ?g/ml between PDR, MDR and XDR-strains of Mtb were not revealed. Comparison of the frequency of high-resistant PDR- and MDR-strains between periods had not revealed differences. In the 3rd period XDR strains with a high level of resistance to H has been detected less frequently than in the first period - 20.4% versus 36.4% (?2=3.883, p=0.049). The detection of H MIC against 41 PDR, MDR, XDR isolates has been revealed a significant variability in the drug resistance level - up 1.6 to 100 ?g/ml. It were no significant differences in the proportion of strains with the same MIC values. A resistance to H in concentrations of less than 12.5 ?g/ml has been detected in 52.5% the strains. By intravenous medication of H it may be possible to achieve a concentration exceeding the threshold for the concrete strain, which can provide an increase in the effectiveness of therapy for MDR/XDR tuberculosis taking into consideration the selectivity of isoniazid action.