CAJ | 학술논문

为了合理地使用抗生素,制定防止耐药菌产生的用药方案,本研究利用近年来提出的防耐药突变浓度(MPC)和耐药选择窗(MSW)这两个药效学(PD)参数,并结合药代动力学(PK)参数,制定恩诺沙星防耐药突变用药方案,控制由嗜水气单胞菌引起的鲫细菌性败血症.研究结果显示,恩诺沙星对该致病性嗜水气单胞菌的体外药效学参数为:最小抑菌浓度(MIC)为0.125μg/mL;2MIC、4MIC、8MIC的抗菌后效应(PAE)分别为(1.67±0.42) h、(2.03±0.17) h、(2.38±0.06) h; MPC为1.125μg/mL; MSW为0.125~1.125μg/mL.根据鲫(Carassius auratus)口灌恩诺沙星后的药代动力学曲线,得出血浆药物浓度>MPC的时间分别为5 h、9.5 h、23 h.PK/PD综合参数:24 h内血药浓度-时间曲线下面积与MIC的比值(AUC24/MIC)分别为137.22、285.15、426.25;峰浓度与MIC的比值(Cmax/MIC)分别为15.05、41.43、52.32.综合血浆药物浓度>MPC的时间超过(24-PAE)h、AUC24/MIC≥100或Cmax/MIC>8的指标,建议恩诺沙星在控制由嗜水气单胞菌引起的鲫细菌性败血症时的给药方案为:给药剂量20 mg/kg体质量,1次/d.根据肌肉内恩诺沙星的药动学方程,药残达到国家限量标准所需时间约为25 d,所以建议休药期不低于25 d.本研究方案也可广泛用于其他水产养殖抗菌药物的防耐药突变用药方案的制定.
위료합리지사용항생소,제정방지내약균산생적용약방안,본연구이용근년래제출적방내약돌변농도(MPC)화내약선택창(MSW)저량개약효학(PD)삼수,병결합약대동역학(PK)삼수,제정은낙사성방내약돌변용약방안,공제유기수기단포균인기적즉세균성패혈증.연구결과현시,은낙사성대해치병성기수기단포균적체외약효학삼수위:최소억균농도(MIC)위0.125μg/mL;2MIC、4MIC、8MIC적항균후효응(PAE)분별위(1.67±0.42) h、(2.03±0.17) h、(2.38±0.06) h; MPC위1.125μg/mL; MSW위0.125~1.125μg/mL.근거즉(Carassius auratus)구관은낙사성후적약대동역학곡선,득출혈장약물농도>MPC적시간분별위5 h、9.5 h、23 h.PK/PD종합삼수:24 h내혈약농도-시간곡선하면적여MIC적비치(AUC24/MIC)분별위137.22、285.15、426.25;봉농도여MIC적비치(Cmax/MIC)분별위15.05、41.43、52.32.종합혈장약물농도>MPC적시간초과(24-PAE)h、AUC24/MIC≥100혹Cmax/MIC>8적지표,건의은낙사성재공제유기수기단포균인기적즉세균성패혈증시적급약방안위:급약제량20 mg/kg체질량,1차/d.근거기육내은낙사성적약동학방정,약잔체도국가한량표준소수시간약위25 d,소이건의휴약기불저우25 d.본연구방안야가엄범용우기타수산양식항균약물적방내약돌변용약방안적제정.
The widespread use of antibiotics in aquaculture has led to increasing problems caused by bacterial re-sistance. Given this, there is an urgent need to develop a medication regimen that prevents the formation of drug resistant bacteria. We estimated a number of pharmacodynamic (including mutant prevent concentration and mu-tant selection window) and pharmacokinetic parameters for the antibiotic drug enrofloxacin. Our objective was to develop a medication regimen against hemorrhagic septicemia in crucian carp(Carassius auratus), a disease caused by Aeromonas hydrophila. The minimal inhibitory concentration (MIC) was 0.125 μg/mL, the post-antibiotic effect (PAE) of enrofloxacin on the pathogenic bacterial strains was observed up to (1.67±0.42) h, (2.03±0.17) h, and (2.38±0.06) h at 2MIC, 4MIC, and 8MIC, respectively, the mutant prevention concentration (MPC) was 1.125 μg/mL, and the mutant selection window was between 0.125 and 1.125 μg/mL. We developed integrated enrofloxacin concentration-time curves for the serum of crucian carp following administration of a range of doses. Enrofloxacin persisted in the serum at concentrations above the MPC for 5 h at a dose of 5 mg/kg;9.5 h at a dose of 10 mg/kg, and 23 h at a dose of 20 mg/kg. The serum PK/PD parameters AUC24/MIC and Cmax/MIC were 137.22 and 15.05, respectively, at a dose of 5 mg/kg, 285.25 and 41.43, respectively, at a dose of 10 mg/kg, and 426.25 and 52.32, respectively, at a dose of 20 mg/kg.The drug remained in the plasma with a concentration>MPC for (24-PAE) h and AUC24/MIC≥100 or Cmax/MIC>8. Our results suggest that hemorrhagic septicemia can be controlled using a dosing regimen of 20 mg/kg enrofloxacin, at intervals of 24 h.The proposed withdrawal time in crucian carp should not be less than 25 d. The methods described in this study also can be used for developing dose guidelines for other anti-bacterial drugs to prevent selection for drug-resistance.