Mouton J W, den Hollander J G
Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University Hospital Rotterdam, The Netherlands.
Antimicrob Agents Chemother. 1994 May;38(5):931-6. doi: 10.1128/AAC.38.5.931.
An in vitro pharmacokinetic model mimicking human serum drug concentrations, based on a dialyzer unit, was developed to study the efficacies of continuous infusion and intermittent administration of ceftazidime over a period of 36 h. The daily dose of ceftazidime was 300 mg/liter/24 h given either as a continuous infusion or as three bolus doses. The intermittent dosing regimen yielded peak and trough concentrations after the fourth dose of 92.3 (standard deviation, 8.0) and 1.4 (standard deviation, 0.9) mg/liter, respectively. Continuous administration yielded concentrations of approximately 20 mg/liter. To study efficacy, three Pseudomonas aeruginosa strains, ATCC 27853, CF4, and CF16, were used. The MICs of ceftazidime for these strains were 1, 4, and 16 mg/liter, respectively. Strain CF16 was killed initially during both regimens and then started to regrow. At the end of the fourth dosing interval, i.e., after 32 h, viable counts showed no difference between the regimens. Strains ATCC 27853 and CF4 were killed initially during both dosing schedules, and after the first dosing interval viable counts were similar. However, after the fourth interval, there was a marked difference between bacterial counts during continuous and intermittent infusion, being 2.2 and 2.8 log10, respectively, demonstrating a greater efficacy during continuous infusion. The results indicate that, in the absence of other factors, a sustained level of ceftazidime around or slightly above the MIC is not high enough to maintain efficacy over more than one (8-h) dosing interval. When sustained concentrations higher than four times the MIC are employed, continuous administration in this model is more efficacious than intermittent dosing.
基于透析器单元，开发了一种模拟人体血清药物浓度的体外药代动力学模型，以研究头孢他啶连续输注和间歇给药36小时的疗效。头孢他啶的日剂量为300mg/升/24小时，可连续输注或分三次推注给药。间歇给药方案在第四次给药后产生的峰浓度和谷浓度分别为92.3（标准差，8.0）和1.4（标准差，0.9）mg/升。连续给药产生的浓度约为20mg/升。为研究疗效，使用了三种铜绿假单胞菌菌株，ATCC 27853、CF4和CF16。头孢他啶对这些菌株的最低抑菌浓度分别为1、4和16mg/升。CF16菌株在两种给药方案开始时均被杀死，然后开始重新生长。在第四个给药间隔结束时，即32小时后，活菌计数显示两种给药方案之间没有差异。ATCC 27853和CF4菌株在两种给药方案开始时均被杀死，在第一个给药间隔后活菌计数相似。然而，在第四个间隔后，连续输注和间歇输注期间的细菌计数存在显著差异，分别为2.2和2.8 log10，表明连续输注期间疗效更佳。结果表明，在没有其他因素的情况下，头孢他啶维持在最低抑菌浓度附近或略高于最低抑菌浓度的水平不足以在超过一个（8小时）给药间隔内维持疗效。当采用高于最低抑菌浓度四倍的持续浓度时，该模型中的连续给药比间歇给药更有效。
