Influence of glutoxim and its derivatives on the growth of mycobacterium tuberculosis (Mtb)

Background. Study of the ability of immunomodulators to potentiate the effect of isoniazide (I) on Mtb isoniazid-resistant strains is a promising line of research in conditions of spreading of the of multidrug-resistant Mtb. Aim is to study isoniazid potentiating activity of commercial immunomodulatory drug Glutoxim (G) and to determine the minimum inhibitory concentration (MIC) of its derivatives (GD). Design . It were investigated H37Rv and two clinical isoniazid-resistant Mtb isolates with mutations in the genes katG , ahpC and inhA from our collection of clinical Mtb strains. Modified "checkerboard method” and microdilution method with Middlebrook 7H9 with OADC, Thiazolyl blue visualization and photometric (630 nm) growth registration were used to evaluate MICs of I, G, their combinations and GDs . Results . G had no effect on the Mtb growth in all tests series. I MIC for H37Rv was 0.062 μg/ml, G(50-3.1 μg/ml) had reduced it to 0.031 μg/ml. Only salt V-007-8 of ten GDs has lowered MIC in twofold, activity of the other GDs did not differ from the isoniazid. Mtb strain with complex of mutations in genes katG (Ser315 → Thr, IIe335 → Va), ahpC _T10 had high level of resistance to isoniazid (23.3 μg/ml), addition of G (50-3,1 μg/ml) has lowered MIC in twofold, salt V-007-8 has decreased MIC in 1.75 time. I MIC for the strain with mutation of inhA-T15 was 0,33-0,5 μg/ml, addition of G enhanced the I activity in 1.6 times. MIC of salt V-007-8 was less than the I MIC in 2 times. Conclusion. G has potentiated the activity of I in 1.6-2 times, MIC of V-007-8 was less than the I MIC in 1.75-2.0 times both sensitive strain H37Rv, and clinical Mtb isolates with mutations in the genes katG, ahpC and inhA.