Linezolid (PNU-100766) is an orally active oxazolidinone antibiotic that has inhibitory activity against a variety of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate Staphylococcus aureus (GISA), vancomycin-resistant Enterococci (VRE), and penicillin-resistant Streptococcus pneumoniae[1]. Linezolid is a 50S ribosomal subunit-specific inhibitor that binds to the 50S ribosomal subunit to inhibit the initial step of protein synthesis[2]. The IC50 of linezolid for protein synthesis in Staphylococcus aureus is 0.3μg/ml, and the IC50 for 50S subunit formation is 0.6μg/ml[3]. Linezolid is indicated for the treatment of skin infections, bacterial pneumonia, and infections complicated by bacteremia[4].
In vitro, Linezolid (1.18 mM) treatment of THP-1 cells infected with Staphylococcus aureus (ATCC 25923 and E19977) for 24 h had no effect on cell viability, but had a significant inhibitory effect on intracellular and extracellular strains[5].
In vivo, Linezolid (50 mg/kg) was intraperitoneally injected into rats with MRSA mediastinitis for 7 days, significantly reducing bacterial counts in the mediastinum and sternum[6].
References:
[1] Perry C M, Jarvis B. Linezolid: a review of its use in the management of serious gram-positive infections[J]. Drugs, 2001, 61: 525-551.
[2] Swaney S M, Aoki H, Ganoza M C, et al. The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria[J]. Antimicrobial agents and chemotherapy, 1998, 42(12): 3251-3255.
[3] Champney W S, Miller M. Linezolid is a specific inhibitor of 50S ribosomal subunit formation in Staphylococcus aureus cells[J]. Current microbiology, 2002, 44: 350-356.
[4] Chen H, Du Y, Xia Q, et al. Role of linezolid combination therapy for serious infections: review of the current evidence[J]. European Journal of Clinical Microbiology & Infectious Diseases, 2020, 39: 1043-1052.
[5] Sandberg A, Jensen K S, Baudoux P, et al. Intra-and extracellular activity of linezolid against Staphylococcus aureus in vivo and in vitro[J]. Journal of antimicrobial chemotherapy, 2010, 65(5): 962-973.
[6] Sacar M, Sacar S, Kaleli I, et al. Efficacy of linezolid in the treatment of mediastinitis due to methicillin-resistant Staphylococcus aureus: an experimental study[J]. International journal of infectious diseases, 2008, 12(4): 396-401.
利奈唑胺（Linezolid; PNU-100766）是一种具有口服活性的恶唑烷酮类抗生素，对多种革兰氏阳性菌具有抑制活性，包括耐甲氧西林金黄色葡萄球菌（MRSA）、糖肽中间体金黄色葡萄球菌（GISA）、耐万古霉素肠球菌（VRE）和耐青霉素肺炎链球菌[1]。Linezolid是一种50S核糖体亚基特异性抑制剂，作用机制是在50S核糖体亚基上结合抑制蛋白质合成的起始步骤[2]。Linezolid对葡萄球菌（Staphylococcus aureus）蛋白质合成的IC50为0.3μg/ml，对50S亚基形成的IC50为0.6μg/ml[3]。Linezolid适用于治疗皮肤感染、细菌性肺炎和菌血症并发的感染[4]。
在体外，Linezolid（1.18mM）处理被金黄色葡萄球菌（ATCC 25923和E19977）感染的THP-1细胞24h，对细胞活力没有影响，但是对细胞内及细胞外的菌株有显著抑制作用[5]。
在体内，Linezolid（50mg/kg）通过腹腔注射治疗MRSA纵隔炎的大鼠7天，显著减少了纵隔和胸骨中的细菌计数[6]。