EVALUATION OF ANTIBIOTIC DIFFUSION INTO CARDIAC VEGETATIONS BY QUANTITATIVE AUTORADIOGRAPHY
EVALUATION OF ANTIBIOTIC DIFFUSION INTO CARDIAC VEGETATIONS BY QUANTITATIVE AUTORADIOGRAPHY
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DOI：
10.1093/infdis/159.5.938
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发表时间：
1989-05-01
影响因子：
6.4
通讯作者：
CARBON, C
中科院分区：
文献类型：
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作者：
CREMIEUX, AC;MAZIERE, B;CARBON, C
细菌性心内膜炎难以治愈的原因多年来一直存在争议。一种解释可能是抗生素在植被内的扩散是异质的。通过放射自显影研究标记的抗生素扩散到兔的营养变异链球菌心内膜炎的大型感染心脏赘生物中，研究了这一假设。感染后10天，在30分钟内静脉注射653 μ Ci [3 H]青霉素、410 μ Ci [3 H]妥布霉素或174 μ Ci [14 C]替考拉宁。输注结束后30分钟（T30），赘生物/血液放射性比率为2.48 ±。1.27，2.49。0.67和3.94 ±。1.19青霉素妥布霉素替考拉宁放射自显影清楚地显示三种药物的分布不同：妥布霉素均匀分布;青霉素更多地集中在外围，但仍能到达赘生物中心;替考拉宁仅集中在外围。替考拉宁在T120时观察到相同的分布模式（即，一个t1/2 β。之后）以及同时输注治疗剂量（15 mg/kg）的冷替考拉宁后。一些抗生素所表现出的扩散梯度可以解释尽管局部浓度很高，但难以对赘生物进行消毒，以及赘生物的大小对治疗反应的有害影响。
The reason bacterial endocarditis is difficult to cure has been controversial for many years. One explanation could be that antibiotic diffusion inside the vegetations is heterogeneous. This hypothesis was investigated by means of an autoradiographic study of diffusion of labeled antibiotics into large infected cardiac vegetations of nutritionally variant Streptococcus endocarditis in rabbits. Ten days after infection, 653 .mu.Ci of [3H]penicillin, 410 .mu.Ci of [3H]tobramycin, or 174 .mu.Ci of [14C]teicoplanin were injected iv over 30 min. Thirty minutes after the end of infusion (T30), vegetation/blood radioactivity ratios were 2.48 .+-. 1.27, 2.49 .+-. 0.67, and 3.94 .+-. 1.19 for penicillin, tobramycin, and teicoplanin, respectively. Autoradiography clearly showed that distribution of the three drugs was different: Tobramycin was homogeneously distributed; penicillin was more concentrated at the periphery but still reached the center of vegetations; teicoplanin was concentrated only at the periphery. The same distribution pattern was observed with teicoplanin at T120 (i.e., one t1/2.beta. later) and also after simultaneous infusion of a therapeutic dose (15 mg/kg) of cold teicoplanin. The diffusion gradient exhibited by some antibiotics could explain the difficulty in sterilizing vegetations despite high local concentrations, and the deleterious effect of the size of the vegetations on the therapeutic response.