[Antimycobacterial activities of rifamycin derivatives]

The Standard Initial Chemotherapy, chemotherapeutic activity of which depends mostly on the two potent bactericidal drugs, INH and RFP, has made a remarkable progress in the treatment of tuberculosis. However, certain difficult situations still remain in the treatment of resistant diseases, mostly in retreatment cases especially resistant to INH and/or RFP, and of the patients who are not able to continue the Standard Regimens because of side effects and/or severe complications with various organ dysfunctions. It is evident that presently available antituberculosis drugs are not potent enough to deal satisfactorily with the above situations, and besides, there has been unsatisfactory chemotherapeutic efficacy against infections caused by Mycobacterium avium complex. The above matters strongly urge our effort to develop new antimycobacterial agents. In the present review, in vitro and in vivo activities of newly synthesized rifamycin derivatives (3'-hydroxy-5'-alkylpiperazinyl-benzoxazinorifamycins, KRMs) were discussed. Of a total of 158 newly synthesized compounds, five (KRM-1648, KRM-1657, KRM-1668, KRM-1674, KRM-2312) were selected due to significantly lower MICs than those of RFP against M. tuberculosis H37Rv and M. intracellulare 31F093T. The MIC90s of these compounds were 16 to 32 times lower than MIC90 of RFP against RFP-susceptible clinical isolates (20 strains) of M. tuberculosis, and 100 times or more lower than MIC90s of RFP against 20 disease-associated M. avium complex strains.(ABSTRACT TRUNCATED AT 250 WORDS)