KILLING OF PSEUDOMONAS-AERUGINOSA DURING CONTINUOUS AND INTERMITTENT INFUSION OF CEFTAZIDIME IN AN IN-VITRO PHARMACOKINETIC MODEL
KILLING OF PSEUDOMONAS-AERUGINOSA DURING CONTINUOUS AND INTERMITTENT INFUSION OF CEFTAZIDIME IN AN IN-VITRO PHARMACOKINETIC MODEL
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DOI：
10.1128/aac.38.5.931
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发表时间：
1994-05-01
影响因子：
4.9
通讯作者：
DENHOLLANDER, JG
中科院分区：
文献类型：
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作者：
MOUTON, JW;DENHOLLANDER, JG
建立了模拟人血药浓度的体外药代动力学模型，用于研究头孢他啶连续输注和间歇给药36 h的疗效。头孢他啶的每日剂量为300 mg/L/24 h，以连续输注或三次推注剂量给药。间歇给药方案在第4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/L。连续给药产生的浓度约为20 mg/L。为了研究功效，使用三种铜绿假单胞菌菌株ATCC 27853、CF 4和CF 16。头孢他啶对这些菌株的MIC分别为1、4和16 mg/L。菌株CF 16在两种方案中最初被杀死，然后开始再生。在第四次给药间隔结束时，即，32小时后，两种方案之间的活菌计数没有差异。在两种给药方案期间，最初杀灭了菌株ATCC 27853和CF 4，在第一个给药间隔后，活菌计数相似。然而，在第四个间隔后，连续和间歇输注期间的细菌计数之间存在显著差异，分别为2.2和2.8 log（10），表明连续输注期间的疗效更高。结果表明，在不存在其他因素的情况下，头孢他啶的持续水平在MIC附近或略高于MIC不足以在一个以上（8小时）给药间隔内维持疗效。当采用高于MIC四倍的持续浓度时，在该模型中连续给药比间歇给药更有效。
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 log(10), 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.