Bailey E M, Rybak M J, Kaatz G W
Department of Pharmacy Services, Detroit Receiving Hospital/University Health Center, Michigan.
Antimicrob Agents Chemother. 1991 Jun;35(6):1089-92. doi: 10.1128/AAC.35.6.1089.
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 micrograms/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 micrograms/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 greater than 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.
评估了蛋白结合对替考拉宁抗金黄色葡萄球菌活性的影响。将替考拉宁在补充阳离子的穆勒-欣顿肉汤（SMHB）中以及在人血清与补充阳离子的穆勒-欣顿肉汤的1:1混合物（PHS-SMHB）中的杀菌率与万古霉素的杀菌率进行了比较。在两个系列中研究了每种药物的八种浓度，范围从15至150微克/毫升，这两个系列分别对应于低剂量（每日一次，6毫克/千克体重）和高剂量（每日一次，30毫克/千克）替考拉宁在血清中达到的浓度。总体而言，替考拉宁的杀菌率低于万古霉素。在有血清存在的情况下，替考拉宁在PHS-SMHB中的杀菌率低于在SMHB中的杀菌率，通常在24小时内CFU仅下降一个对数10。在两种培养基中，高浓度和低浓度替考拉宁的杀菌率均无统计学差异。此外，两种药物在SMHB中均未表现出浓度依赖性杀菌作用。还研究了替考拉宁和万古霉素在血清超滤物与SMHB的1:1混合物中60微克/毫升浓度下的杀菌率。值得注意的是，血清超滤物的存在均未影响两种药物的杀菌率。这一发现与替考拉宁的高度蛋白结合（据报道在未稀释血清中大于90%）一致，并进一步证实了只有游离药物对微生物有活性这一假设。这些数据支持蛋白结合是替考拉宁抗金黄色葡萄球菌活性的一个影响因素。
