Young Katherine
Merck Research Laboratories, Rahway, New Jersey, USA.
Curr Protoc Pharmacol. 2006 Oct;Chapter 13:Unit13A.6. doi: 10.1002/0471141755.ph13a06s34.
The study of resistance is vital to the discovery and development of new antibacterial agents. Consider the case where the resistance frequency (the proportion of cells within a population that exhibit a resistance phenotype to the agent under study) of an agent is such that, in an average infection, a mutant resistant to the agent is likely to already exist. This compound will not be useful in the clinic as a single agent, since this mutant can survive its administration, leading to potential clinical failure. This unit provides protocols for determining the frequency and rate of resistance to antibacterial agents, as well as generating resistant mutants for mechanism of action determinations or for use in antibacterial discovery or development programs.
耐药性研究对于新型抗菌药物的发现和开发至关重要。设想这样一种情况:某种药物的耐药频率(即群体中对所研究药物表现出耐药表型的细胞比例)使得在一般感染中,很可能已经存在对该药物耐药的突变体。这种化合物作为单一药物在临床上将毫无用处,因为这种突变体能够在给药后存活下来,从而导致潜在的临床治疗失败。本单元提供了用于确定对抗菌药物的耐药频率和速率的方案,以及产生耐药突变体以用于作用机制研究或抗菌药物发现与开发项目的方案。