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成人万古霉素治疗药物监测:美国卫生系统药剂师学会、美国感染病学会和感染病学会药剂师协会共识推荐总结。

Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.

机构信息

Anti-Infective Research Laboratory, Pharmacy Practice-4148, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit,MI 48201, USA.

出版信息

Pharmacotherapy. 2009 Nov;29(11):1275-9. doi: 10.1592/phco.29.11.1275.

Abstract

Vancomycin is a commonly used antibiotic due to its effectiveness in treating serious gram-positive infections caused by methicillin-resistant Staphylococcus aureus. As commercial drug assays and a multitude of pharmacokinetic data from a variety of patient populations are widely available, therapeutic monitoring of serum vancomycin concentrations is frequently performed by clinicians, with the expectation that targeting the concentrations within a relatively narrow range can minimize toxicity yet still achieve therapeutic success. Much debate exists, however, over the value of routine therapeutic monitoring of vancomycin levels because of conflicting evidence regarding the ability of serum concentrations to predict effectiveness or prevent toxicity. In addition, studies have suggested that the potential for nephrotoxicity or ototoxicity with vancomycin monotherapy is minimal at conventional dosages of 1 g (15 mg/kg) every 12 hours. However, increased rates of nephrotoxicity have recently been reported with doses of 4 g/day or higher. The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists published a consensus statement on therapeutic monitoring of serum vancomycin levels in adults. These organizations established an expert panel to review the scientific data and controversies associated with vancomycin monitoring and to make recommendations based on the available evidence. As the members of this panel, we summarize the conclusions and highlight the recommendations from the consensus statement. We determined that the area under the concentration-time curve (AUC): minimum inhibitory concentration (MIC) ratio is the most useful pharmacodynamic parameter to predict vancomycin effectiveness and suggested a target ratio of 400 or greater to eradicate S. aureus. In addition, trough serum concentration monitoring is the most accurate and practical method to monitor vancomycin serum levels. Increasing trough concentrations to 15-20 mg/L to attain the target AUC:MIC ratio may be desirable but is currently not supported by clinical trials. Alternative therapies should be considered in patients with S. aureus infections that demonstrate a vancomycin MIC of 2 mg/L or greater because the target AUC:MIC ratio ( 400) is unlikely to be achieved in this setting. Increasing the dosage to result in higher trough concentrations may increase the potential for toxicity; however additional clinical experience is required to determine the extent.

摘要

万古霉素是一种常用的抗生素,因为它在治疗由耐甲氧西林金黄色葡萄球菌引起的严重革兰氏阳性感染方面非常有效。由于商业药物检测和来自各种患者群体的大量药代动力学数据广泛可用,临床医生经常进行血清万古霉素浓度的治疗监测,期望将浓度目标定在相对较窄的范围内可以最大限度地降低毒性,同时仍能取得治疗成功。然而,由于关于血清浓度是否能够预测疗效或预防毒性的证据存在冲突,关于常规监测万古霉素水平的价值存在很多争议。此外,研究表明,在常规剂量(1 克,每 12 小时 15 毫克/千克)的万古霉素单药治疗中,潜在的肾毒性或耳毒性极小。然而,最近报告的更高剂量(4 克/天或更高剂量)的肾毒性发生率增加。美国卫生系统药剂师学会、传染病学会和感染性疾病药剂师学会发布了成人血清万古霉素水平治疗监测的共识声明。这些组织成立了一个专家小组,审查与万古霉素监测相关的科学数据和争议,并根据现有证据提出建议。作为该小组的成员,我们总结了结论并突出了共识声明中的建议。我们确定浓度-时间曲线下面积(AUC):最低抑菌浓度(MIC)比值是预测万古霉素疗效最有用的药效学参数,并建议目标比值为 400 或更高,以消除金黄色葡萄球菌。此外,谷浓度监测是监测万古霉素血清水平最准确和实用的方法。增加谷浓度至 15-20 毫克/升以达到目标 AUC:MIC 比值可能是理想的,但目前尚未得到临床试验的支持。对于金黄色葡萄球菌感染患者,如果万古霉素 MIC 为 2 毫克/升或更高,应考虑替代治疗,因为在这种情况下不太可能达到目标 AUC:MIC 比值(400)。增加剂量以提高谷浓度可能会增加毒性的可能性;但是,需要更多的临床经验来确定程度。

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