科研课题研究_猪传染性胸膜炎药效评价模型的建立与应用

猪传染性胸膜炎药效评价模型的建立与应用

本文报道麻保沙星等24种抗菌药物对血清学1型猪胸膜肺炎放线杆菌（APP）的体外最小抑菌浓度（MIC）及麻保沙星对实验性猪传染性胸膜肺炎的药效学研究，同时对血浆药物浓度进行了监测。以试管两倍稀释法测定麻保沙星等抗菌药物对猪胸膜肺炎放线杆菌的体外MIC。结果表明，对APP高度敏感的药物有麻保沙星、环丙沙星、单诺沙星、沙拉沙星、二氟沙星、氧氟沙星、洛美沙星及头孢噻呋，其MIC值分别为0.01、0.01、0.03、0.03、0.03、0.03、0.06和0.01mg/ml；敏感的药物有青霉素G、恩诺沙星、氨苄西林、阿莫西林、头孢氨苄、盐酸土霉素、盐酸金霉素、盐酸多西环素、氯霉素及氟甲砜霉素，其MIC值分别为0.12IU/ml、0.12、0.12、0.25、1、0.5、0.5、0.5、0.5和0.5mg/ml；较不敏感或耐药的药物有硫酸红霉素4mg/ml、盐酸林可霉素8mg/ml、硫酸卡那霉素32mg/ml和SM2、SMD、SMZ，对APP的MIC均大于128mg/ml。体外抑菌试验结果表明，麻保沙星对猪胸膜肺炎放线杆菌具有良好的抗菌活性，其作用与环丙沙星、头孢噻呋相同，优于恩诺沙星、单诺沙星和氧氟沙星及其它对照药物。60头健康杜洛克×长白×大白三元杂交断奶仔猪，7~8周龄，随机分为6组，每组10头。按每kg体重颈部气管接种7.5×10~6菌落形成单位的猪胸膜肺炎放线杆菌，可诱发出具有典型猪传染性胸膜肺炎临床症状的疾病模型。表现

为接种后2~3h，猪呼吸困难、精神沉郁、体温升高，部分猪出现短暂性呕吐。接种后4~6h，猪直肠体温达到最高值，平均升高1.5~2℃。接种后10天，从前腔静脉采血分离血清，经酶联免疫吸附法检测呈阳性抗体反应，证明猪感染了传染性胸膜肺炎。感染猪用麻保沙星进行治疗（高、中、低剂量治疗组的给药剂量分别为5.0、2.5、1.25mg/kg），以恩诺沙星作对照（2.5mg/kg），一天一次，连续用药4天。各治疗组的治愈率分别为90%、80%和60%，恩诺沙星组为60%，感染对照组的死亡率为90%。采用高效液相色谱法（HPLC）测定感染猪多剂量给药治疗期间的血浆药物浓度，紫外检测器检测，波长为290nm。麻保沙星高、中、低剂量组给药后24h的血浆药物浓度(盨.E.)分别为0.43±0.05、0.17±0.02和0.07±0.01mg/ml。给药后24h各剂量组的血浆药物浓度均高于麻保沙星对APP的MIC，可以有效杀灭细菌，缓解临床症状，达到治疗目的。本研究证实，麻保沙星对血清学1型猪胸膜肺炎放线杆菌具有优良的体内外抗菌活性，其体外MIC为0.01mg/ml；以2.5~5.0mg/kg体重颈部肌注给药，每天一次，连用4天，对实验性猪传染性胸膜肺炎具有较好的疗效。

英文摘要：

The minimum inhibitory concentrations(MICs)of marbofloxacin and23 other antimicrobial agents were tested against porcine Actinobacillus Pleuropneumoniae(APP)in vitro.The efficacy against porcine contagious pleuropneumonia and plasma concentration monitoring of marbofloxacin in pigs were investigated.The MICs of marbofloxacin and other antimicrobial agents were determined by the two-fold dilution method in vitro.Marbofloxacin,

ciprofloxacin,danofloxacin,sarafloxacin,difloxacin,ofloxacin,lomefloxacin and ceftiofur were highly sensitive to APP,and the MICs were0.01,0.01,0.03, 0.03,0.03,0.03,0.06and0.01mg/ml,respectively.Penicillin G,enrofloxacin, ampicillin,amoxicillin,cephalexin,oxytetracycline,chlortetracycline, doxycycline,chloramphenicol and florfenicol were sensitive to APP,and the MICs were0.12IU/ml,0.12,0.12,0.25,1,0.5,0.5,0.5,0.5and0.5mg/ml, respectively.Erythromycin,lincomycin,kanamycin,sulfamethazine(SM2), sulfamethoxydiazine(SMD)and sulfamethoxazole(SMZ)were less sensitive or resistant to APP,and the MICs were4,8,32,>128,>128and>128mg/ml, respectively.The results showed that marbofloxacin had the similar activity against APP as ceftiofur and ciprofloxacin,but was superior to enrofloxacin, danofloxacin,ofloxacin and other agents.Sixty crossed pigs aged seven to eight weeks were randomly assigned to six groups,ten pigs for each group.Five groups of pigs were induced porcine contagious pleuropneumonia by intratracheally inoculation with bacterial suspension containing7.5×10~6 colony forming units(CFU)of serotype1APP and the disease model was indicated by clinical signs,rectal temperature,ELISA test,necropy and isolation of the pathogen.One group of pigs was used as healthy control.Three groups of infected pigs were treated with marbofloxacin at a dosage of5.0,2.5,and1.25 mg/kg b.w.,respectively,and one group of infected pigs was treated as the positive control with enrofloxacin at a dosage of2.5mg/kg b.w..The medication was carried out by intramuscular administration once daily for four consecutive