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Antibiotics: Pharmacokinetics, toxicity, resistance and multidrug efflux pumps

机译：抗生素：药代动力学，毒性，抗性和多药泵泵

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摘要

The discovery of penicillin followed by streptomycin, tetracycline, cephalosporins and other natural, semi-synthetic and synthetic antimicrobials completely revolutionized medicine by reducing human morbidity and mortality from most of the common infections. However, shortly after they were introduced to clinical practice, the development of resistance was emerged. The decreasing interest from antibiotic industry in spite of rapid global emergence of antibiotic resistance is a tough dilemma from the pointview of public health. The efficiency of antimicrobial treatment is determined by both pharmacokinetics and pharmacodynamics. In spite of their selective toxicity, antibiotics still cause severe, life threatening adverse reactions in host body mostly due to defective drug metabolism or excessive dosing regimen. The present article aims at updating current knowledge on pharmacokinetics/pharmacodynam ics concepts and models, toxicity of antibiotics as well as antibiotic resistance mechanisms, resistome analyses and search for novel antibiotic resistance determinants with special emphasis given to the state-of-the-art regarding multidrug efflux pumps and their additional physiological functions in stress adaptation and virulence of bacteria. All these issues are highly linked to each other and not only important for most efficient and prolonged use of current antibiotics, but also for discovery and development of new antibiotics and novel inhibitors of antibiotic resistance determinants of pathogens. (C) 2016 Elsevier Inc. All rights reserved.
机译：青霉素的发现，然后是链霉素，四环素，头孢菌素和其他天然，半合成和合成抗微生物通过减少来自大多数常见感染的人的发病率和死亡率完全旋转化药物。但是，在临床实践中介绍后不久，抵抗的发展出现。尽管抗生素抗性快速全球出现的抗生素出现的抗生素行业的兴趣降低是来自公共卫生地点的艰难的困境。抗微生物治疗的效率由药代动力学和药效学确定。尽管他们的选择性毒性，抗生素仍然导致宿主体内的严重威胁不良反应主要是由于药物代谢或过量给药方案过度的药物。本文旨在更新目前关于药代动力学/药物学委员会概念和模型的知识，抗生素的毒性以及抗生素抗性机制，抵抗力分析和寻找新的抗生素抗性决定簇，特别强调对最先进的抗生素抗性决定簇多rrugEfflux泵及其在细菌应激适应和毒力中的额外生理功能。所有这些问题彼此高度相关，而且对最有效和长期使用目前的抗生素来说，也是重要的，而且对于发现和开发新的抗生素和病原体抗生素抗性决定簇的新抑制剂。 （c）2016年Elsevier Inc.保留所有权利。

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