In vitro microbiological characterization of novel cyclic homopentapeptides, CP-101,680 and CP-163,234, for animal health use

Two cyclic homopentapeptides, CP-101,680 and CP-163,234 [6a-(3',4'-dichloro pheny- amino) analogs of viomycin and capreomycin, respectively], were iden tified as novel antibacterial agents for the treatment of animal disease, e specially for livestock respiratory disease. The in vitro microbiological c haracterization of both CP-101,680 and CP-163,234 was carried out using the ir parent compounds, viomycin and capreomycin, as controls. This characteri zation included antibacterial spectrum, influence of media, inoculum size, pH, EDTA, polymixin B nonapeptide (PMBN), serum, cell-free protein synthesi s inhibition, and time-kill kinetics. Our results indicated that the capreo mycin analog, CP-163,234, showed slightly improved in vitro potency over th e viomycin analog, CP-101,680. Both analogs showed very potent cell-free pr otein synthesis inhibition activity and were bactericidal against Pasteurel la haemolytica, P. multocida and Actinobacillus pleuropneumoniae at the lev el of 4 times and 8 times MICs. CP-163,234 was bactericidal at the level of 4x and 8x MIC against E. coli, but re-growth was observed after 24 hours i ncubation at both concentrations of CP-101,680.