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An Evaluation of Antibiotic Resistance: Structure-Activity Relationship Studies of Tetracyclic Indolines as A Novel Class of Resistance-Modifying Agents for MRSA u26 Analysis of Recent FDA Regulations on Antibiotic Use in Livestock

机译:抗生素抗药性的评估:四环吲哚啉作为新型抗药性修饰剂用于MRSA的结构-活性关系研究 u26最新FDA畜牧业抗生素使用法规分析

摘要

While the rate at which resistance develops against antimicrobials rises, research and development for new antimicrobials declines. By placing selective pressure on bacteria we are inadvertently forcing bacteria into expressing and propagating genes conferring high levels of resistance. Continued misuse and overuse of antibiotics, in light of the evident problem developing, must be resolved. To find a resolve, a multidisciplinary and multifaceted approach must be taken which involves 1) research and development of novel antimicrobial agents and 2) governmental regulation.Strides in new antimicrobial drug development largely revolve around making old antibiotics usable again. Resistance-Modifying Agents (RMAs) act to re-sensitize resistant bacteria to antibiotics. Foreseeably, while these compounds have shown efficacy and certainly are of value in the present crisis, it is a short-term solution in light of the evidently rapid and dynamic capability of bacteria to respond evolutionarily. Nonetheless, a new class of RMAs, currently being researched and developed at Wang lab, hope to extend RMA lifespan through a model of synthetic compound development that targets gene expression.Both clinically and community-acquired resistance contribute to the demolishment of a critical building block (antibiotics) of modern medicine. Arguably the most nonsensical piece of the puzzle is subtherapeutic antibiotic use in livestock, which accounts for 80% of all antibiotic use in the United States12. FDA regulations are seemingly the only feasible way to fix the problem, and yet their efforts in recent regulatory measures not only contain major loopholes, but seem altogether to be largely barren of any significant resolutions.
机译:虽然对抗菌素产生耐药性的速率增加,但对新抗菌素的研究与开发却减少了。通过对细菌施加选择性压力,我们无意间迫使细菌表达和传播赋予高水平抗性的基因。根据明显的问题发展,必须解决继续滥用和过度使用抗生素的问题。为了找到解决方案,必须采取一种多学科,多方面的方法,其中包括1)新型抗菌剂的研究和开发以及2)政府法规。在新抗菌药物开发方面的进步主要围绕使旧抗生素再次可用。抗药性改良剂(RMA)可使抗药性细菌对抗生素重新敏感。可以预见,尽管这些化合物已显示出功效,并且在当前危机中当然具有价值,但鉴于细菌对进化的响应具有明显的快速和动态能力,这是一种短期解决方案。尽管如此,Wang实验室目前正在研发的新型RMA希望通过针对基因表达的合成化合物开发模型来延长RMA的寿命,临床和社区获得的耐药性都有助于破坏关键构件。 (抗生素)的现代医学。可以说,最无意义的难题是家畜中亚治疗性抗生素的使用,占美国所有抗生素使用的80%12。 FDA法规似乎是解决问题的唯一可行方法,然而,它们在最新法规措施中的努力不仅存在重大漏洞,而且在任何重大解决方案中似乎都显得很贫乏。

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    Cleaver Lakota K;

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