IN-VITRO MICROBIOLOGICAL CHARACTERIZATION OF NOVEL MACROLIDE CP-163,505 FOR ANIMAL HEALTH SPECIFIC USE

A novel 16-membered-ring macrolide agent (CP-163,505, a reductive amin ation derivative of repromicin) was identified as an antibacterial aga inst Pasteurella haemolytica, P. multocida and Actinobacillus pleuropn eumoniae, important etiological agents of livestock respiratory diseas e. In vitro MIC50/90 analysis revealed that CP-163,505 was more potent (4x) than tilmicosin against P. multocida, and equivalent to tilmicos in against P. haemolytica and A. pleuropneumoniae. In time kill kineti c studies, CP-163,505 showed bactericidal activity against P. haemolyt ica, P. multocida and A. pleuropneumoniae and bacteriostatic activity against E. coli at 8 times its MIG. In vitro, CP-163,505 was more pote nt in alkaline pH (16 similar to 32x) and less potent in the presence of excess cations (Mg+2 and Ca+2, 4x). EDTA and PMBN increased CP-163, 505 potency against E. coli (4x) but not against the other species. Si milar results were obtained with erythromycin A and tilmicosin, which were used as controls. From our data, we hypothesize that Pasteurella and Actinobacillus have an outer membrane significantly different from that of the typical enteric Gram-negative bacterium E. coli.