为了有效的抗菌治疗,医师需要使用临床微生物学实验室提供的敏感性断点进行定性检测.本文总结了用于建立替迪唑胺临床实验室标准研究所(CLSI)断点的关键组件。首先,使用最近的监测和临床试验分离物的体外研究确定了对相关生物的最小抑制浓度(MIC)分布,包括葡萄球菌,链球菌,还有肠球菌.在感染的动物模型中的研究确定了以与人类相同的剂量施用磷酸替迪唑胺后的抗菌功效和存活率。药代动力学和药效学分析检查了血浆浓度与针对靶生物体的MIC之间的关系。最后,临床试验通过MIC评估临床和微生物学结局.对所有这些数据进行评估和组合,以获得已批准的金黄色葡萄球菌的替地唑胺的CLSI敏感性标准≤0.5μg/mL,化脓性链球菌,无乳链球菌,和粪肠球菌,≤0.25μg/mL的角度。
For effective antibacterial therapy, physicians require qualitative test results using susceptibility
breakpoints provided by clinical microbiology laboratories. This article summarizes the key components used to establish the Clinical Laboratory Standards Institute (CLSI)
breakpoints for tedizolid. First, in vitro studies using recent surveillance and clinical trial isolates ascertained minimal inhibitory concentration (MIC) distributions against pertinent organisms, including staphylococci, streptococci, and enterococci. Studies in animal models of infection determined rates of antibacterial efficacy and survival following administration of tedizolid phosphate at doses equivalent to those in humans. Pharmacokinetic and pharmacodynamic analyses examined the relationship between plasma concentrations and MICs against the target organism. Finally, clinical trials assessed clinical and microbiologic outcomes by MIC. All these data were evaluated and combined to obtain the ratified CLSI susceptibility criteria for tedizolid of ≤0.5μg/mL for Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Enterococcus faecalis and ≤0.25μg/mL for Streptococcus anginosus group.