title: In vitro microbiological characterization of novel macrolide CP-163,505 for animal health specific use.
abstract: A novel 16-membered-ring macrolide agent (CP-163,505, a reductive amination derivative of repromicin) was identified as an antibacterial against Pasteurella haemolytica, P. multocida and Actinobacillus pleuropneumoniae, important etiological agents of livestock respiratory disease. In vitro MIC50/90 analysis revealed that CP-163,505 was more potent (4x) than tilmicosin against P. multocida, and equivalent to tilmicosin against P. haemolytica and A. pleuropneumoniae. In time kill kinetic studies, CP-163,505 showed bactericidal activity against P. haemolytica, P. multocida and A. pleuropneumoniae and bacteriostatic activity against E. coli at 8 times its MIC. In vitro, CP-163,505 was more potent in alkaline pH (16 approximately 32 x ) 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. Similar 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.
authors.affiliation: Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Norcia
authors.forename: S B
authors.initials: SB
authors.lastname: Seibel
authors.forename: B J
authors.initials: BJ
authors.lastname: Kamicker
authors.forename: M A
authors.initials: MA
authors.lastname: Lemay
authors.forename: S C
authors.initials: SC
authors.lastname: Lilley
authors.forename: S J
authors.initials: SJ
authors.lastname: Hecker
authors.forename: J M
authors.initials: JM
authors.lastname: Bergeron
authors.forename: J A
authors.initials: JA
authors.lastname: Retsema
authors.forename: S F
authors.initials: SF
authors.lastname: Hayashi
mesh_terms: D016977:Actinobacillus pleuropneumoniae / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D018942:Macrolides; D016978:Mannheimia haemolytica / Q000187:drug effects; D008566:Membranes / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D016979:Pasteurella multocida / Q000187:drug effects; D015645:Tylosin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C111763:CP 163505; D018942:Macrolides; D004917:Erythromycin; C052319:tilmicosin; D015645:Tylosin