[In vitro activities of new rifamycin derivatives against Mycobacterium tuberculosis and M. avium complex]

The in vitro anti-M. tuberculosis and anti-M. avium complex activities of five new rifamycin derivatives, KRM1648, KRM1657, KRM1668, KRM1674 and KRM2312, provided by Kanegafuchi Chem. Ind. Co. Japan were evaluated and compared with those of rifampicin (RFP) and rifabutin (RBU). Antimycobacterial activity was tested by broth dilution method using Kirchner's liquid medium supplemented with 10% bovine serum. The MICs 90 (micrograms/ml) of all five KRMs and RBU for 20 clinical isolates of M. tuberculosis were 0.035-0.07, whereas that of RFP was 1.25. The new rifamycin derivatives showed 16 to 32 times lower MICs than those of RFP against M. tuberculosis. All five KRMs inhibited 100% of 20 clinical isolates of M. avium complex at a concentration of 1.25 micrograms/ml, while only 35% and 10% of the strains were inhibited by the same concentration of RBU and RFP, respectively. The MICs 90 (micrograms/ml) for the strains tested were 0.07-0.3 for all five KRMs, and 5 and 40-80 for RBU and RFP, respectively. The new rifamycin derivatives were 16 times more active than RBU, which was 8 times more active than RFP. The new rifamycin derivatives were far more effective against M. tuberculosis in vitro than RFP, and their superiority to RBU which showed the effect superior to RFP was notable in in vitro anti-M. avium complex activities.