新リファマイシン系薬剤KRM-1648のin vitro抗結核菌作用

抄録

In vitro antimicrobial activities of the benzoxazinorifamycin derivative KRM -1648 (KRM) against 50 strains of Mycobacterium tuberculosis isolated from patients with mainly intractable pulmonary tuberculosis were studied. MIC ₉₀ values of KRM, rifabutin (RBT) and rifampicin (RFP) for RFP -sensitive strains (27 strains; defined as those with MIC RFP values of <1.56μ g/ml) were 0.013, 0.1 and 0.4μ g/ml, respectively, when determined by the agar dilution method using 7H11 medium. MIC ₉₀ values of KRM, RBT, and RFP for RFP -resistant strains (23 strains; defined as those having MIC RFP values of ≥ 1.56μ g/ml) were 100, 12.5 and > 100μ g/ml/, respectively. MICs of KRM against 50 clinical isolates of M. tuberculosis distributed over a much lower range than those of RFP. KRM showed more potent antimicrobial activity than RBT against the organisms with low MIC values (≥ 1.56μ g/ml/), while it was not so active as RBT against the organisms with high MIC values (pg/m/). Cross-resistance between KRM and RFP or RBT was observed for M. tuberculosis.