In vivo susceptibility of Mycobacterium ulcerans to KRM-1648, a new benzoxazinorifamycin, in comparison with rifampicin. Anti-mycobacterial activity of KRM-1648.
The antibacterial effects of a new benzoxazinorifamycin, KRM-1648 (3'-hydroxy-5'-(4-isobutyl-1-piperazinyl, CAS 129791-92-0), against Mycobacterium ulcerans were evaluated in vivo in mouse foot pads, and the results were compared against those obtained with rifampicin (rifampin, CAS 13292-46-1). When mice were fed with the drugs from the day of footpad inoculations, KRM-1648, at concentrations of 0.001% and higher, mixed in mouse food, was effective in inhibiting the growth of M. ulcerans in the foot pads, and the effects were bactericidal. Effects of KRM-1648 at 0.0005% were bacteriostatic. Similar results were obtained with rifampicin, but only at concentrations of 0.008% and above. In established infection, i.e., when M. ulcerans were growing actively in footpads, bactericidal effects were observed with KRM-1648 at concentrations of 0.002% and above; to obtain similar results with rifampicin, the minimum dose was 0.032%. Thus, the results suggest the superiority of KRM-1648 over rifampicin in the treatment of M. ulcerans infection. The possibility of using KRM-1648 in combination with other antimycobacterial agents is discussed.
Dhople
A M
AM
Department of Biological Sciences, Florida Institute of Technology, Melbourne, Florida, USA. adhople@fit.edu
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005528:Foot / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D019911:Mycobacterium ulcerans / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C068980:KRM 1648; D012293:Rifampin