虹鳟杀鲑气单胞菌耐药性研究与盐酸多西环素给药方案制定  

Drug resistance of Aeromonas salmonicides in rainbow trout and formulation of doxycycline hydrochloride dosing regimen

作　　者：刘博[1,2] 张培 彭嘉琪 程波 赵雅贤[3] 穆迎春[2] 孙慧武[2] LIU Bo;ZHANG Pei;PENG Jia-qi;CHENG Bo;ZHAO Ya-xian;MU Ying-chun;SUN Hui-wu(National Demonstration Center for Experimental Fisheries Science Education,Shanghai Ocean University,Shanghai 201306,China;Key Laboratory of Aquatic Product Quality and Safety Control,Ministry of Agriculture and Rural Affairs,Chinese Academy of Fishery Sciences,Beijing 100141,China;Beidaihe Central Experiment Station,Chinese Academy of Fishery Sciences,Qinhuangdao 066100,Hebei,China)

机构地区：[1]上海海洋大学水产科学国家级实验教学示范中心,上海201306 [2]中国水产科学研究院,农业农村部水产品质量安全控制重点实验室,北京100141 [3]中国水产科学研究院北戴河中心实验站,河北秦皇岛066100

出　　处：《淡水渔业》2023年第6期69-79,共11页Freshwater Fisheries

基　　金：世界自然基金会(WWT)蔚蓝量球基金:海水养殖抗菌药物科学使用技术研究与推广应用(PORO001427);现代农业产业技术体系建设专项资金(CARS-46)。

摘　　要：为科学制定虹鳟(Oncorhynchus mykiss)杀鲑气单胞菌(Aeromonas salmonicida)病的给药方案,对3株分离自虹鳟的杀鲑气单胞菌采用纸片扩散法(K-B法)进行24种抗生素耐药性测定,并对其中4种敏感且批准使用的抗生素进行体外药效学实验,研究20、30、40和60 mg/kg盐酸多西环素在染病虹鳟体内的药代动力学特征。结果显示:3株杀鲑气单胞菌对复方新诺明、磺胺异恶唑、青霉素、阿莫西林、头孢唑林耐药,对盐酸多西环素最敏感,其最小抑菌浓度(MIC)为0.5μg/mL,最小杀菌浓度(MBC)在2~4μg/mL之间,防耐药突变浓度(MPC)为1μg/mL;恩诺沙星的MIC在0.25~1μg/mL之间,MBC为4μg/mL,MPC为1.5μg/mL;氟苯尼考的MIC为1μg/mL,MBC为8μg/mL,MPC为2μg/mL;硫酸新霉素MIC为4μg/mL,MBC为8μg/mL,MPC为12μg/mL。40 mg/kg剂量单次给药,盐酸多西环素在患病虹鳟血浆中的峰浓度为1.19μg/mL,达峰时间为4 h,且血药浓度维持在MIC以上16 h,可以满足虹鳟杀鲑气单胞菌病治疗需要。60 mg/kg剂量单次给药,盐酸多西环素在患病虹鳟血浆、肌肉、肾脏和肝脏中药物浓度维持在MIC以上的时间分别为23、18、23.5和23.5 h,在患病虹鳟血浆、肾脏和肝脏中药物浓度维持在MPC之上的时间分别为6、23.5和23.5 h,此使用剂量既能达到虹鳟杀鲑气单胞菌治疗作用,又能有效防止产生耐药性。A total of 24 antibiotic resistance determinations were carried out on three strains of Aeromonas salmonicida isolated from rainbow trout,to scientifically formulate the dosing protocol of Aeromonas salmonicida disease in rainbow trout(Oncorhynchus mykiss).Meanwhile,in vitro pharmacodynamic experiments were conducted on four sensitive and approved antibiotics to study the pharmacokinetic characteristics of doxycycline hydrochloride at 20,30,40,and 60 mg/kg in infected rainbow trout.The results showed that three strains of Aeromonas salmonicide were resistant to compound trimoxazole,sulfamethoxazole,penicillin,amoxicillin,and cefazolin,and were most sensitive to doxycycline hydrochloride,with a minimum inhibitory concentration(MIC)of 0.5μg/mL,a minimum bactericidal concentration(MBC)between 2~4μg/mL,and an anti-drug resistance mutation concentration(MPC)of 1μg/mL.The minimum inhibitory concentration(MIC)of enrofloxacin was between 0.25~1μg/mL,the minimum bactericidal concentration(MBC)was 4μg/mL,and the anti-drug resistance mutation concentration(MPC)was 1.5μg/mL.The minimum inhibitory concentration(MIC)of florfenicol was 1μg/mL,the minimum bactericidal concentration(MBC)was 8μg/mL,and the anti-resistance mutation concentration(MPC)was 2μg/mL;The minimum inhibitory concentration(MIC)of neomycin sulfate was 4μg/mL,the minimum bactericidal concentration(MBC)was 8μg/mL,and the anti-resistance mutation concentration(MPC)was 12μg/mL.With a single dose of 40 mg/kg,the peak concentration of doxycycline hydrochloride in the plasma of diseased rainbow trout was 1.19μg/mL,the peak time was 4 h,and the plasma concentration was maintained above MIC for 16 h,which could meet the treatment needs of rainbow trout salmonicide.With a single dose of 60 mg/kg,the drug concentrations of doxycycline hydrochloride in the plasma,muscle,kidney and liver of the diseased rainbow trout were maintained above MIC for 23,18,23.5,and 23.5 h,respectively,and the drug concentrations in the plasma,kidney and liver of the diseased rain

关 键 词：杀鲑气单胞菌(Aeromonas salmonicida) 虹鳟(Oncorhynchus mykiss) 耐药 盐酸多西环素 给药方案 

分 类 号：S948[农业科学—水产养殖]