COMPARATIVE EFFECT OF PROTEIN-BINDING ON THE KILLING ACTIVITIES OF TEICOPLANIN AND VANCOMYCIN
COMPARATIVE EFFECT OF PROTEIN-BINDING ON THE KILLING ACTIVITIES OF TEICOPLANIN AND VANCOMYCIN
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DOI：
10.1128/aac.35.6.1089
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发表时间：
1991-06-01
影响因子：
4.9
通讯作者：
KAATZ, GW
中科院分区：
文献类型：
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作者：
BAILEY, EM;RYBAK, MJ;KAATZ, GW
研究了蛋白结合对teicoplanin抗金黄色葡萄球菌活性的影响。比较了teicoplanin在阳离子补充穆勒-辛顿肉汤（SMHB）和人血清与阳离子补充穆勒-辛顿肉汤（PHS-SMHB） 1:1混合中的杀菌率与万古霉素的杀菌率。每种药物的8个浓度范围为15 - 150 μ g/ml，分为两个系列进行研究，这些浓度对应于低剂量（6 mg/kg体重每日一次）和高剂量（30 mg/kg每日一次）替柯planin在血清中的浓度。总体而言，替柯planin的杀菌率低于万古霉素。在血清存在的情况下，PHS-SMHB中teicoplanin的杀菌率低于SMHB，通常导致24小时内CFU仅下降1 log10。高浓度和低浓度替柯planin在两种培养基中的杀菌率均无统计学差异。此外，两种药剂对SMHB的杀伤作用均不明显。以60 μ g/ml的血清超滤液与SMHB的1:1混合，研究了替柯planin和万古霉素的杀菌率。结果表明，两种药剂的杀菌率均不受血清超滤液存在的影响。这一发现与teicoplanin与蛋白质的高度结合（据报道，在未稀释的血清中，teicoplanin与蛋白质的结合率为90%）相一致，并进一步证实了只有游离药物对微生物有活性的假设。这些数据支持蛋白质结合是teicoplanin抗金黄色葡萄球菌活性的一个因素。
The effect of protein binding on the activity of teicoplanin against Staphylococcus aureus was evaluated. Bactericidal rates of teicoplanin in cation-supplemented Mueller-Hinton broth (SMHB) and in a 1:1 mixture of pooled human serum and cation-supplemented Mueller-Hinton broth (PHS-SMHB) were compared with those of vancomycin. Eight concentrations of each drug ranging from 15 to 150-mu-g/ml were studied in two series which correspond to the concentrations in serum achieved with low- (6 mg/kg of body weight once daily) and high-dose (30 mg/kg once daily) teicoplanin. Overall, the bactericidal rate of teicoplanin was lower than that of vancomycin. In the presence of serum, the bactericidal rate of teicoplanin in PHS-SMHB was lower than that in SMHB, often resulting in only one log10 drop in CFU over a 24-h period. There was no statistical difference in the bactericidal rates of high- and low-concentration teicoplanin in either medium. Additionally, concentration-dependent killing in SMHB was not evident with either agent. The bactericidal rates of teicoplanin and vancomycin in a 1:1 mixture of serum ultrafiltrate and SMHB at 60-mu-g/ml were also studied. It was noted that the bactericidal rate of neither agent was affected by the presence of serum ultrafiltrate. This finding is consistent with teicoplanin's high degree of protein binding (reported to be > 90% in undiluted serum) and further substantiates the hypothesis that only the free drug is active against microorganisms. These data support protein binding as being a factor in teicoplanin activity against S. aureus.