Ambrose Paul G
Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, New York 12208, USA.
Treat Respir Med. 2005;4 Suppl 1:5-11.
Since the early 1960s, considerable advancements have been made to standardize and provide quality assurance for clinical susceptibility testing procedures of antimicrobial agents. Controversy, however, remains as to the interpretation of clinical laboratory susceptibility test results. While some feel susceptibility breakpoints should only detect resistance mechanisms, others believe they should predict a high probability of clinical response. This has resulted in confusion among clinicians, as it has been apparent for some time that there can be discordance between interpretive test results and clinical response to therapy (generally cures of infections caused by resistant pathogens). Nearly simultaneous with the beginning of the standardization process for clinical susceptibility testing procedures, the first penicillin-resistant Streptococcus pneumoniae isolates were detected. During the ensuing decades, penicillin-resistant pneumococci became a greater clinical concern, resulting in macrolides emerging as safe therapeutic alternatives to beta-lactam agents for the treatment of community-acquired respiratory tract infections. During the last 10 years, the incidence of pneumococcal isolates with elevated macrolide minimum inhibitory concentration (MIC) values has also increased, yet the debate over the clinical meaning of these statistics persists. The youthful science of pharmacokinetics-pharmacodynamics provides a useful platform to determine which pneumococcal strains with elevated MIC values can be treated with contemporary dosing regimens and also facilitates the proper selection of antimicrobial breakpoints for all antimicrobial classes, including the newer macrolides.
自20世纪60年代初以来，在抗菌药物临床药敏试验程序的标准化和质量保证方面已经取得了相当大的进展。然而，对于临床实验室药敏试验结果的解释仍存在争议。一些人认为药敏断点仅应检测耐药机制，而另一些人则认为它们应预测临床反应的高概率。这导致临床医生之间产生困惑，因为一段时间以来很明显，解释性试验结果与治疗的临床反应（通常是由耐药病原体引起的感染的治愈情况）之间可能存在不一致。几乎与临床药敏试验程序标准化进程开始的同时，首次检测到对青霉素耐药的肺炎链球菌分离株。在随后的几十年里，耐青霉素肺炎球菌成为更大的临床关注点，导致大环内酯类药物成为治疗社区获得性呼吸道感染时β-内酰胺类药物的安全治疗替代药物。在过去10年中，大环内酯类药物最低抑菌浓度（MIC）值升高的肺炎球菌分离株的发生率也有所增加，但关于这些统计数据临床意义的争论仍在继续。年轻的药代动力学-药效学科学提供了一个有用的平台，以确定哪些MIC值升高的肺炎球菌菌株可以用当代给药方案治疗，并且还有助于为所有抗菌药物类别，包括新型大环内酯类药物，正确选择抗菌药物断点。
