The pharmacokinetics and pharmacodynamics of vancomycin in clinical practice: evidence and uncertainties.
The pharmacokinetics and pharmacodynamics of vancomycin in clinical practice: evidence and uncertainties.
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万古霉素在临床实践中的药代动力学和药效学：证据和不确定性。
DOI：
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发表时间：
2013
影响因子：
5.2
通讯作者：
E. Tacconelli
中科院分区：
文献类型：
--
作者：
S. Vandecasteele;A. D. Vriese;E. Tacconelli
自20世纪50年代末以来，万古霉素一直被广泛使用。尽管近年来推出了几种新的有价值的抗革兰氏阳性抗生素，葡萄球菌对万古霉素的敏感性也在下降，但它仍然是治疗由耐甲氧西林葡萄球菌引起的菌血症的金标准。万古霉素具有明显的剂量-反应和剂量-毒性关系。人们普遍认为，AUC/MIC模型可以很好地预测这些相关性，目标水平>；400是临床分界点。这个模型的实验基础并不像人们通常认为的那样可靠，也没有包括万古霉素耐药性中的几个重要问题，如生物被膜耐药性和接种效应。基于这个模型，目前的给药指南建议间歇给药，目标谷值为15-20 mg/L。已经提出了根据肾功能进行剂量调整的建议，但尚未得到验证。临床数据也支持使用持续输注，目标平台水平为20-25 mg/L，具有类似的疗效，但代价是肾毒性较低。尽管万古霉素经过了几十年的密集临床应用和大量的研究和出版物，但在剂量-反应关系的高要求和剂量-毒性关系的严重缺陷之间，万古霉素的最佳剂量策略仍有待建立。
Vancomycin has been used extensively since the late 1950s. Despite the introduction of several new valuable anti-Gram-positive antibiotics during recent years and the waning susceptibility of staphylococci to vancomycin, it remains the gold standard for the treatment of bacteraemia caused by methicillin-resistant staphylococci. Vancomycin has clear dose-response and dose-toxicity correlations. It is widely accepted that these correlations are best predicted by the AUC/MIC model, with target levels of >400 being the clinical cut-off. The experimental base of this model is less robust than frequently believed, and several important issues in vancomycin resistance, such as biofilm resistance and the inoculum effect, are not included. Based on this model, current dosing guidelines propose intermittent dosing of vancomycin with target trough levels of 15-20 mg/L. Dose adaptations according to renal function have been proposed but are not yet validated. Clinical data also support the use of continuous infusion with target plateau levels of 20-25 mg/L, with similar efficacy at the cost of lower nephrotoxicity. Despite decades of intense clinical use and numerous studies and publications, the optimal dosing strategy for vancomycin reconciling the high needs of the dose-response relationship with the serious drawbacks of the dose-toxicity relationship remains to be established.
影响因子：
11.8
作者：
Stryjewski, Martin E.;Szczech, Lynda A.;Fowler, Vance G., Jr.
通讯作者：
Fowler, Vance G., Jr.
影响因子：
9.6
作者：
Walkey, Allan J.;O'Donnell, Max R.;Wiener, Renda Soylemez
通讯作者：
Wiener, Renda Soylemez