SIGNIFICANCE OF EXTRAVASCULAR PROTEIN-BINDING FOR ANTIMICROBIAL PHARMACODYNAMICS IN AN INVITRO CAPILLARY MODEL OF INFECTION
SIGNIFICANCE OF EXTRAVASCULAR PROTEIN-BINDING FOR ANTIMICROBIAL PHARMACODYNAMICS IN AN INVITRO CAPILLARY MODEL OF INFECTION
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DOI：
10.1128/aac.34.1.98
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发表时间：
1990-01-01
影响因子：
4.9
通讯作者：
ZINNER, SH
中科院分区：
文献类型：
--
作者：
DUDLEY, MN;BLASER, J;ZINNER, SH
在体外感染毛细血管模型中研究了血管外空间蛋白结合对抗菌药物药效学的影响。模拟口服500毫克双氯西林(.apprx。96%结合)或头孢氨苄（< 5%结合）每6小时给药，共4剂。还研究了10倍剂量的双氯西林，以确定药物浓度对减少蛋白质存在下的细菌杀灭的影响。将金黄色葡萄球菌ATCC 25923接种于填充穆勒-辛顿肉汤或穆勒-辛顿肉汤加25%人血清的外周腔中。在24小时内收集了连续的细菌计数样本。在前6小时，血清的存在显著降低了双氯西林对细菌的杀伤作用，而头孢氨苄对细菌的杀伤作用则没有（双向方差分析，F = 6.04, P < 0.05），但在24小时内则没有。在含血清的培养室中，双氯西林活性的降低随着剂量的增加而持续存在。这些数据表明，尽管高结合药物在含蛋白质的血管外空间获得更高的总药物浓度，但在该模型中，蛋白质结合在治疗的早期阶段降低了杀菌活性。
The effect of protein binding in an "extravascular" space on antimicrobial pharmacodynamics was studied in an in vitro capillary model of infection. Simulated 500-mg oral doses of dicloxacillin (.apprx. 96% bound) or cephalexin (< 5% bound) were administered every 6 h for four doses. A 10-fold-higher dose of dicloxacillin was also studied to determine the effect of drug concentration on the reduction of bacterial killing in the presence of protein. Staphylococcus aureus ATCC 25923 was inoculated into peripheral chambers filled with either Mueller-Hinton broth or Mueller-Hinton broth plus 25% human serum. Serial samples for bacterial counts were collected over 24 h. The presence of serum in the chambers significantly reduced bacterial killing by dicloxacillin but not by cephalexin during the first 6 h (two-way analysis of variance, F = 6.04, P < 0.05) but not at 24 h. Reduction of dicloxacillin activity in serum-containing chambers persisted with the higher dose. These data suggest that despite attaining higher total drug concentrations in protein-containing extravascular spaces with highly bound drugs, protein binding reduces bactericidal activity during the early stages of treatment in this model.