Mohr John F, Murray Barbara E
Department of Internal Medicine, Division of Infectious Diseases and Center for Emerging and Re-emerging Pathogens, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Clin Infect Dis. 2007 Jun 15;44(12):1536-42. doi: 10.1086/518451. Epub 2007 May 4.
Since the discovery, development, and US Food and Drug Administration approval of vancomycin in the 1950s, this agent has remained a mainstay for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, because of the development of new antistaphylococcal antibiotics and reports of vancomycin failures, the utility of vancomycin has recently been questioned. Although vancomycin did not undergo the strict US Food and Drug Administration approval process that is in place today to demonstrate efficacy, there is considerable information available that sheds light on the role vancomycin has in infectious diseases pharmacotherapy today. In addition, although we look to in vitro susceptibility testing to assess vancomycin activity against S. aureus, we have come to appreciate that resistance of S. aureus to vancomycin can be a continuous--rather than a categorical--phenomenon. This has resulted in clinical microbiology laboratories having difficulty identifying S. aureus that may not respond to conventional doses of vancomycin. A better understanding is needed of the pharmacodynamic relationship between vancomycin and MRSA as relates to optimal dosing strategies, including consideration for loading doses, and development of rational categorical breakpoints for susceptibility based on clinical outcomes. By better understanding these critical issues, it may be possible to optimize the use of vancomycin, resulting in a cost-effective treatment option for many patients infected with MRSA.
自20世纪50年代发现、研发并获得美国食品药品监督管理局批准以来，万古霉素一直是治疗耐甲氧西林金黄色葡萄球菌（MRSA）感染的主要药物。然而，由于新型抗葡萄球菌抗生素的出现以及万古霉素治疗失败的报道，万古霉素的效用最近受到了质疑。尽管万古霉素并未经历如今美国食品药品监督管理局所采用的严格审批流程来证明其疗效，但仍有大量信息能够阐明万古霉素在当今传染病药物治疗中的作用。此外，尽管我们依靠体外药敏试验来评估万古霉素对金黄色葡萄球菌的活性，但我们逐渐认识到金黄色葡萄球菌对万古霉素的耐药可能是一种持续的——而非绝对的——现象。这导致临床微生物实验室难以鉴定出可能对常规剂量万古霉素无反应的金黄色葡萄球菌。需要更好地理解万古霉素与MRSA之间的药效学关系，这涉及到最佳给药策略，包括考虑负荷剂量，以及根据临床结果制定合理的敏感性分类断点。通过更好地理解这些关键问题，有可能优化万古霉素的使用，为许多感染MRSA的患者提供一种具有成本效益的治疗选择。
