Aspects of the antituberculous activity of 27753-RP, a new semisynthetic derivative of griselimycine.
The antituberculous activity of 27753-RP (RP), a new semisynthetic derivative of griselimycine, was determined both in vitro and in vivo, and its activity against atypical mycobacteria was also studied in vitro. 1) The minimal inhibitory concentration of RP against H37Rv and its mutants resistant to streptomycin, isoniazide, kanamycin, rifampicin and enviomycin was 0.5 microgram/ml in liquid media, showing no cross-resistance. However, loss of potency occurred in Ogawa's egg media, and 50 micrograms/ml of RP were required for inhibition of growth. 2) In the therapeutic study of experimental tuberculosis in mice, RP was shown to have a remarkable effect. In particular, when treatment was started immediately after infection, RP showed a therapeutic efficacy comparable to that of rifampicin, although a double dose of the drug was required. When treatment was started 3 weeks after infection, RP was inferior to rifampicin in therapeutic efficacy. 3) RP also showed excellent antituberculous activity against experimental tuberculosis in guinea-pigs. Twice-a-week treatment had a therapeutic efficacy comparable to that obtained by daily treatment, but with an increased dosage. 4) Among atypical mycobacteria, RP showed some degree of activity against Mycobacterium kansasii in vitro, while its activity against M. intracellulare appeared to be extremely low.
D000818:Animals; D000900:Anti-Bacterial Agents; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009170:Nontuberculous Mycobacteria / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D010455:Peptides; C028747:27753R.P.; D012293:Rifampin