Norcia L J, Seibel S B, Kamicker B J, Lemay M A, Lilley S C, Hecker S J, Bergeron J M, Retsema J A, Hayashi S F
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
J Antibiot (Tokyo). 1998 Feb;51(2):136-44. doi: 10.7164/antibiotics.51.136.
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.
一种新型的16元环大环内酯类药物（CP-163,505，瑞普米星的还原胺化衍生物）被鉴定为对溶血巴斯德氏菌、多杀性巴氏杆菌和胸膜肺炎放线杆菌具有抗菌活性，这些是家畜呼吸道疾病的重要病原体。体外MIC50/90分析表明，CP-163,505对多杀性巴氏杆菌的活性比替米考星强（4倍），对溶血巴斯德氏菌和胸膜肺炎放线杆菌的活性与替米考星相当。在时间杀菌动力学研究中，CP-163,505对溶血巴斯德氏菌、多杀性巴氏杆菌和胸膜肺炎放线杆菌表现出杀菌活性，对大肠杆菌在其MIC的8倍浓度时表现出抑菌活性。在体外，CP-163,505在碱性pH条件下活性更强（约16至32倍），在存在过量阳离子（Mg+2和Ca+2，4倍）时活性较弱。EDTA和PMBN可增强CP-163,505对大肠杆菌的活性（4倍），但对其他菌种无效。作为对照的红霉素A和替米考星也得到了类似结果。根据我们的数据，我们推测巴斯德氏菌属和放线杆菌属的外膜与典型的肠道革兰氏阴性菌大肠杆菌有显著差异。
