Maire P, Barbaut X, Vergnaud J M, el Brouzi M, Confesson M A, Pivot C, Chuzeville M, Ivanoff N, Brazier J L, Jelliffe R W
ADCAPT, Hopital A. Charial, Hospices Civils de Lyon, Francheville, France.
Int J Biomed Comput. 1994 Jun;36(1-2):77-85. doi: 10.1016/0020-7101(94)90097-3.
The treatment of endocarditis often requires prolonged antibiotic therapy. Individualized drug dosage regimens have made such therapy possible even in patients with impaired renal function. However, the problem of efficacy remains. Especially for aminoglycosides, it would be a useful guide to have at least an approximate idea of the concentration of an antibiotic within an endocardial vegetation. This study was designed to develop software to model the drug concentrations at different layers within spherical vegetations to provide a guide during clinical therapy of patients with endocarditis. A general model describing the diffusion of antibiotics in spheres has now been developed and interfaced with the USC*PACK PC Clinical Programs in order to compute and plot concentrations, within the vegetation, based on the regimen given to the patient and the diffusitivity of the antibiotic into the vegetation. Some preliminary results of this research, which are still in progress, are presented. Diffusion into simulated spherical vegetations has been computed for different treatment regimens for endocarditis: amikacin or netilmicin and vancomycin were given to three elderly patients (3 women, 74, 75 and 92 years old, with initial estimated creatinine clearances of 51, 36, and 31 ml/min/1.73 m2, respectively). Although Amikacin has a low diffusivity, the concentrations, even in the center of the vegetation, appear to be effective. The effects of various regimens, including a 'once-a-day' aminoglycoside regimen, are presented.
心内膜炎的治疗通常需要长期使用抗生素。个体化的药物剂量方案使得即使在肾功能受损的患者中也能进行这种治疗。然而，疗效问题依然存在。特别是对于氨基糖苷类药物，了解心内膜赘生物内抗生素的浓度至少有一个大致的概念将是一个有用的指导。本研究旨在开发软件，以模拟球形赘生物不同层内的药物浓度，为心内膜炎患者的临床治疗提供指导。现在已经开发了一个描述抗生素在球体中扩散的通用模型，并与USC*PACK PC临床程序接口，以便根据给予患者的治疗方案和抗生素向赘生物中的扩散率来计算和绘制赘生物内的浓度。本文展示了这项仍在进行中的研究的一些初步结果。针对心内膜炎的不同治疗方案，已计算出抗生素向模拟球形赘生物中的扩散情况：对三名老年患者（3名女性，年龄分别为74岁、75岁和92岁，初始估计肌酐清除率分别为51、36和31 ml/min/1.73 m2）给予阿米卡星或奈替米星以及万古霉素。尽管阿米卡星的扩散率较低，但即使在赘生物中心的浓度似乎也有效。文中呈现了包括“每日一次”氨基糖苷类治疗方案在内的各种治疗方案的效果。
