Linezolid, approved for clinical use since 2000, has become an important addition to the anti-Gram-positive infection armamentarium. This oxazolidinone drug has in vitro and in vivo activity against essentially all Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The in vitro activity of linezolid was well documented prior to its clinical application, and several ongoing surveillance studies demonstrated consistent and potent results during the subsequent years of clinical use. Emergence of resistance has been limited and associated with invasive procedures, deep organ involvement, presence of foreign material and mainly prolonged therapy. Non-susceptible organisms usually demonstrate alterations in the 23S rRNA target, which remain the main resistance mechanism observed in enterococci; although a few reports have described the detection of cfr-mediated resistance in Enterococcus faecalis. S. aureus isolates non-susceptible to linezolid remain rare in large surveillance studies. Most isolates harbour 23S rRNA mutations; however, cfr-carrying MRSA isolates have been observed in the United States and elsewhere. It is still uncertain whether the occurrences of such isolates are becoming more prevalent. Coagulase-negative isolates (CoNS) resistant to linezolid were uncommon following clinical approval. Surveillance data have indicated that CoNS isolates, mainly Staphylococcus epidermidis, currently account for the majority of Gram-positive organisms displaying elevated MIC results to linezolid. In addition, these isolates frequently demonstrate complex and numerous resistance mechanisms, such as alterations in the ribosomal proteins L3 and/or L4 and/or presence of cfr and/or modifications in 23S rRNA. The knowledge acquired during the past decades on this initially used oxazolidinone has been utilized for developing new candidate agents, such as tedizolid and radezolid, and as linezolid patents soon begin to expire, generic brands will certainly become available. These events will likely establish a new chapter for this successful class of antimicrobial agents.

中文翻译：

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利奈唑胺更新：经过十多年的临床使用和相关耐药机制的总结，体外活性稳定。

自2000年以来获准用于临床的利奈唑胺已成为抗革兰氏阳性感染武器库的重要补充。该恶唑烷酮药物对基本上所有革兰氏阳性生物都有体外和体内活性，包括耐甲氧西林的金黄色葡萄球菌（MRSA）和耐万古霉素的肠球菌（VRE）。在临床应用之前，利奈唑胺的体外活性已得到充分记录，并且正在进行的监测研究表明，在随后的临床使用年限中，结果一致且有效。抗药性的出现受到限制，并且与侵入性手术，深部器官受累，异物的存在以及主要是延长的治疗有关。非敏感生物通常会表现出23S rRNA靶标的改变，这仍然是肠球菌中观察到的主要耐药机制；尽管有一些报道描述了在粪肠球菌中检测到cfr介导的耐药性。对利奈唑胺不敏感的金黄色葡萄球菌分离株在大型监测研究中仍然很少见。多数分离株带有23S rRNA突变。但是，在美国和其他地方已经发现了携带cfr的MRSA分离株。仍不确定此类分离物的发生是否越来越普遍。临床批准后，罕见的抗利奈唑胺凝固酶阴性分离株（CoNS）罕见。监测数据表明，CoNS分离株（主要是表皮葡萄球菌）目前占大多数革兰氏阳性生物的相对于利奈唑胺显示出较高的MIC结果。此外，这些分离物经常表现出复杂且众多的抗性机制，例如核糖体蛋白L3和/或L4的改变和/或cfr的存在和/或23S rRNA的修饰。在过去的几十年中，关于这种最初使用的恶唑烷酮的知识已被用于开发新的候选药物，例如泰地唑酯和雷地唑胺，而随着利奈唑胺的专利即将开始失效，仿制药肯定会可用。这些事件很可能为这一成功的抗菌剂类别树立新的篇章。如泰地唑酯和雷地唑胺，随着利奈唑胺专利即将开始失效，仿制药肯定会面世。这些事件很可能为这一成功的抗菌剂类别树立新的篇章。如泰地唑酯和雷地唑胺，随着利奈唑胺专利即将开始失效，仿制药肯定会面世。这些事件可能会为这一成功的抗菌剂类别树立新的篇章。