Hashemian Seyed Mohammad Reza, Farhadi Tayebeh, Ganjparvar Mojdeh
Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Drug Des Devel Ther. 2018 Jun 18;12:1759-1767. doi: 10.2147/DDDT.S164515. eCollection 2018.
Linezolid can be considered as the first member of the class of oxazolidinone antibiotics. The compound is a synthetic antibiotic that inhibits bacterial protein synthesis through binding to rRNA. It also inhibits the creation of the initiation complex during protein synthesis which can reduce the length of the developed peptide chains, and decrease the rate of reaction of translation elongation. Linezolid has been approved for the treatment of infections caused by vancomycin-resistant , hospital-acquired pneumonia caused by , complicated skin and skin structure infections (SSSIs), uncomplicated SSSIs caused by methicillin-susceptible or , and community-acquired pneumonia caused by . Analysis of high-resolution structures of linezolid has demonstrated that it binds a deep cleft of the 50S ribosomal subunit that is surrounded by 23S rRNA nucleotides. Mutation of 23S rRNA was shown to be a linezolid resistance mechanism. Besides, mutations in specific regions of ribosomal proteins uL3 and uL4 are increasingly associated with linezolid resistance. However, these proteins are located further away from the bound drug. The methicillin-resistant and vancomycin-resistant enterococci are considered the most common Gram-positive bacteria found in intensive care units (ICUs), and linezolid, as an antimicrobial drug, is commonly utilized to treat infected ICU patients. The drug has favorable in vitro and in vivo activity against the mentioned organisms and is considered as a useful antibiotic to treat infections in the ICU.
利奈唑胺可被视为恶唑烷酮类抗生素中的首个成员。该化合物是一种合成抗生素，通过与核糖体RNA（rRNA）结合来抑制细菌蛋白质合成。它还抑制蛋白质合成过程中起始复合物的形成，这会减少所形成肽链的长度，并降低翻译延伸的反应速率。利奈唑胺已被批准用于治疗由耐万古霉素的 引起的感染、由 引起的医院获得性肺炎、复杂性皮肤及皮肤结构感染（SSSIs）、由对甲氧西林敏感的 或 引起的非复杂性SSSIs，以及由 引起的社区获得性肺炎。对利奈唑胺高分辨率结构的分析表明，它结合在50S核糖体亚基的一个深裂隙中，该裂隙被23S rRNA核苷酸环绕。23S rRNA的突变被证明是一种利奈唑胺耐药机制。此外，核糖体蛋白uL3和uL4特定区域的突变与利奈唑胺耐药性的关联日益增加。然而，这些蛋白质距离结合的药物更远。耐甲氧西林的 和耐万古霉素的肠球菌被认为是重症监护病房（ICUs）中最常见的革兰氏阳性菌，而利奈唑胺作为一种抗菌药物，通常用于治疗ICU中受感染的患者。该药物对上述微生物具有良好的体外和体内活性，被认为是治疗ICU感染的一种有用抗生素。
