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Emergence of Multi-Drug Resistant Gram-Positive Bacteria and New Active Antibiotics

机译:多重耐药革兰氏阳性细菌和新型活性抗生素的出现

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The extensive use of antimicrobials in community as well as nosocomial environments during the last half century has created a pressure that is able to select resistant microorganisms, transforming this "evolution" into one of the most dangerous phenomena of the last twenty years. Two different aspects of the same problem have to be examined: the appearance of "new opportunistic multiresistant microorganisms, and the assembly of resistance related genetic elements from heterologous sources in well known pathogens. In both cases, the bacterial response to this selective pressure is the acquisition and spread of a variety of determinants due to mutations of normal cellular genes, acquisition of foreign resistance determinants or a combination of these two genetic mechanisms.All these processes are generally present in contemporary Gram-positive pathogens that have evolved and spread over the last twenty years becoming a special, and perhaps unique, threat for the emergence of resistance in our era.Streptococcus pneumoniae, Streptococcus pyogenes, Staphy loco ecus aureus, and Enterococci, which are currently isolated, are no longer the same organisms isolated 50 years ago: becoming multiresistant or predominant opportunistic pathogens, they have paid a "biological price" to the use of antibiotics in a short time period. Once established, a resistant strain may persist under selective pressure from numerous antimicrobials, furthermore, some resistances are widespread and others local, but it is still unclear why some bacterial lineages achieve epidemic spread whereas others, that are equally resistant, do not.Many interesting new antibiotics have been developed and recently marketed or are undergoing phase III clinical trials. These drugs, some of which have novel mechanisms of action, may help to counterbalance and, if used appropriately, prevent the spread of resistant bacteria.This review will consider some of these new drugs such as streptogramins, oxazolidinones, the newer fluoroquinolones, ketolides, daptomycin, new glycopeptides, glycylcyclines and the newer cephalosporins.
机译:在过去的半个世纪中,抗菌素在社区和医院环境中的广泛使用产生了一种压力,该压力能够选择抗性微生物,从而将这种“进化”转变为过去二十年来最危险的现象之一。必须研究同一问题的两个不同方面:“新的机会性多抗性微生物的出现,以及已知病原体中来自异源的抗性相关遗传元件的组装。在这两种情况下,细菌对这种选择压力的反应都是由于正常细胞基因突变,获得外来抗性决定簇或这两种遗传机制的结合而获得各种决定簇的获得和传播。所有这些过程通常存在于当代革兰氏阳性病原体中,这些病原体在过去的一个世纪里一直在进化和传播。二十年来,它已成为当今时代耐药性出现的特殊威胁,也许是独特的威胁。目前分离的肺炎链球菌,化脓性链球菌,金黄色葡萄球菌和肠球菌已不再是50年前分离的相同生物:成为多药耐药或主要的机会病原体,他们付出了“价格”以在短时间内使用抗生素。一旦建立,耐药菌株可能会在众多抗生素的选择性压力下持续存在,此外,一些耐药菌广泛存在而另一些耐药菌是局部的,但仍不清楚为什么某些细菌谱系实现了流行扩散,而其他同样耐药的细菌谱系却没有。已经开发出新的抗生素,并且最近已经上市销售,或者正在进行III期临床试验。这些药物,其中一些具有新颖的作用机制,可能有助于平衡,并且,如果使用得当,还可以防止耐药菌的传播。本文将考虑一些新药,例如链霉菌素,恶唑烷酮,较新的氟喹诺酮类药物,酮类内酯,达托霉素,新糖肽,糖基环素和新的头孢菌素。

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