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抗菌药物敏感性试验的新概念:突变预防浓度和突变选择窗方法。

New concepts in antimicrobial susceptibility testing: the mutant prevention concentration and mutant selection window approach.

作者信息

Blondeau Joseph M

机构信息

Department of Clinical Microbiology, Royal University Hospital, Canada S7N 0W8.

出版信息

Vet Dermatol. 2009 Oct;20(5-6):383-96. doi: 10.1111/j.1365-3164.2009.00856.x.

DOI:10.1111/j.1365-3164.2009.00856.x
PMID:20178475
Abstract

Current measurements of antimicrobial susceptibility or resistance utilize a standardized bacterial inoculum (10(5) cfu/mL) exposed to varying drug concentrations in a test tube. Following incubation under ideal conditions, the lowest drug concentration inhibiting growth is the minimum inhibitory concentration (MIC). When the MIC exceeds the amount of drug that can be safely achieved in the body, we call these microorganisms resistant; established breakpoints for various 'bug-drug' combinations are used to categorize microorganisms as susceptible, intermediate or resistant. MIC testing has been used for decades to guide antimicrobial therapy and remains an important measurement for infectious diseases. More recently, the mutant prevention concentration (MPC) has been described as a novel measurement of in vitro susceptibility or resistance and is based on the testing of larger bacterial inocula, i.e. > or =10(9) cfu/mL - such as those associated with some infections in humans and animals. MPC defines the lowest drug concentration required to block the growth of the least susceptible cell present in high density bacterial populations. MPC testing applies to microorganisms considered susceptible to the drug by MIC testing. The mutant selection window (MSW) defines the 'danger zone' for therapeutic drug concentrations. Minimizing the length of time the drug concentration remains in the MSW may reduce the likelihood for resistance selection during therapy. The MSW is bordered by the MIC and MPC values and the drug concentration range between the measured MIC and MPC values defines the MSW. MPC values, when considered with drug pharmacology, may allow prediction on the probability of resistance selection when bacteria are exposed to antimicrobial agents during therapy for infectious diseases. In today's environment, resistance prevention should be a goal of antimicrobial therapy.

摘要

目前对抗菌药物敏感性或耐药性的检测是在试管中使用标准化的细菌接种物(10⁵ cfu/mL),使其暴露于不同的药物浓度下。在理想条件下孵育后,抑制生长的最低药物浓度即为最低抑菌浓度(MIC)。当MIC超过体内可安全达到的药物量时,我们称这些微生物具有耐药性;各种“细菌 - 药物”组合的既定断点用于将微生物分类为敏感、中介或耐药。MIC检测已用于指导抗菌治疗数十年,并且仍然是传染病的一项重要检测指标。最近,突变预防浓度(MPC)已被描述为一种体外敏感性或耐药性的新检测指标,它基于对更大细菌接种量的检测,即≥10⁹ cfu/mL,例如与人类和动物的某些感染相关的接种量。MPC定义了阻止高密度细菌群体中最不敏感细胞生长所需的最低药物浓度。MPC检测适用于通过MIC检测被认为对该药物敏感的微生物。突变选择窗(MSW)定义了治疗药物浓度的“危险区”。尽量缩短药物浓度停留在MSW内的时间可能会降低治疗期间耐药性选择的可能性。MSW以MIC和MPC值为边界,测量的MIC和MPC值之间的药物浓度范围定义了MSW。当与药物药理学一起考虑时,MPC值可能有助于预测在传染病治疗期间细菌接触抗菌药物时耐药性选择的概率。在当今环境下,预防耐药性应是抗菌治疗的目标。

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