Garraffo R, Drugeon H B, Dellamonica P, Bernard E, Lapalus P
Laboratoire de Pharmacologie Expérimentale et Clinique, Centre Hospitalier Universitaire, Nice, France.
Antimicrob Agents Chemother. 1990 Apr;34(4):614-21. doi: 10.1128/AAC.34.4.614.
The pharmacokinetics and serum killing curves of amikacin, which was administered by a 30-minute intravenous infusion of single doses of 7.5 mg/kg and then 15 mg/kg, were investigated in six healthy volunteers who received the two doses in a crossover study with a washout period of 20 days. The serum killing curves were determined for four bacterial species: Escherichia coli, Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa. All strains were serum resistant, and the bactericidal activity was analyzed by separating the early phase (first 5 h) and the late phase (24 h) of the killing curve. For the early phase, the bactericidal activity was evaluated by correlating an index of surviving bacteria with amikacin concentrations. This methodology allowed determination of two parameters: the maximal effective concentration and the lowest effective concentration. For the late phase, the threshold values separating bacteriostatic and bactericidal activities were lower than 10 mg/liter for each strain. The concentration dependence of amikacin bactericidal activity was confirmed for Escherichia coli and Enterobacter cloacae and, to a lesser extent, for Serratia marcescens and Pseudomonas aeruginosa. Correlation of these data with amikacin pharmacokinetic data in volunteers indicated that a daily dose of 15 mg/kg may be effective in the treatment of Escherichia coli and Enterobacter cloacae infections. For Pseudomonas aeruginosa and Serratia marcescens, the partially time-dependent activity probably necessitates two daily administrations and combination with another antibiotic.
在一项交叉研究中，对6名健康志愿者进行了研究，他们接受单剂量7.5mg/kg然后15mg/kg的阿米卡星静脉输注30分钟，洗脱期为20天，以此来研究阿米卡星的药代动力学和血清杀菌曲线。测定了四种细菌的血清杀菌曲线：大肠杆菌、粘质沙雷氏菌、阴沟肠杆菌和铜绿假单胞菌。所有菌株均对血清耐药，并通过分离杀菌曲线的早期阶段（最初5小时）和晚期阶段（24小时）来分析杀菌活性。在早期阶段，通过将存活细菌指数与阿米卡星浓度相关联来评估杀菌活性。这种方法可以确定两个参数：最大有效浓度和最低有效浓度。在晚期阶段，每种菌株的抑菌和杀菌活性的阈值均低于10mg/L。对于大肠杆菌和阴沟肠杆菌，证实了阿米卡星杀菌活性的浓度依赖性，对于粘质沙雷氏菌和铜绿假单胞菌，在较小程度上也证实了这一点。这些数据与志愿者体内阿米卡星药代动力学数据的相关性表明，每日剂量15mg/kg可能对治疗大肠杆菌和阴沟肠杆菌感染有效。对于铜绿假单胞菌和粘质沙雷氏菌，部分时间依赖性活性可能需要每日给药两次并与另一种抗生素联合使用。
