Paladino Joseph A
CPL Associates LLC, 3980 Sheridan Drive, Suite 501, Amherst, NY 14226, USA.
Am J Health Syst Pharm. 2002 Dec 15;59(24):2413-25. doi: 10.1093/ajhp/59.24.2413.
The pharmacology, antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effects of linezolid are reviewed. Linezolid, the only oxazolidinone antimicrobial approved for use in the United States, has significant activity against gram-positive bacteria, including penicillin-, cephalosporin-, and vancomycin-resistant species. Linezolid inhibits bacterial protein synthesis via binding to the 50S ribosomal subunit to prevent translation. The drug lacks cross-resistance with other antimicrobials. Linezolid is primarily excreted renally as unchanged drug. The measured plasma half-life of four to five hours permits twice-daily administration for all indicated infections. Virtually complete oral bioavailability allows for 1:1 conversion between the intravenous and oral dosage forms. Controlled comparative clinical trials demonstrate that linezolid is effective in the treatment of vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA) infections, nosocomial and community-acquired pneumonia, and skin and skin-structure infections due to susceptible organisms. The recommended dosage is 600 mg i.v. or p.o. twice daily for all indications except uncomplicated skin and skin-structure infections (400 mg twice daily); adjustments for mild to moderate renal or hepatic impairment are not necessary. Clinically important interactions with monoamine oxidase inhibitors have not been observed. Reversible myelosuppression has been observed in a few patients. Linezolid has gram-positive activity comparable to that of vancomycin, is effective in a variety of infections, and is well tolerated, with diarrhea, headache, and nausea being the most frequently reported adverse effects. Linezolid provides a reasonable therapeutic alternative for patients with vancomycin-resistant E. faecium infections and patients infected with MRSA who cannot tolerate vancomycin.
本文综述了利奈唑胺的药理学、抗菌活性、药代动力学、临床疗效及不良反应。利奈唑胺是美国唯一获批使用的恶唑烷酮类抗菌药物，对革兰氏阳性菌具有显著活性，包括对青霉素、头孢菌素及万古霉素耐药的菌株。利奈唑胺通过与50S核糖体亚基结合来抑制细菌蛋白质合成，从而阻止翻译过程。该药物与其他抗菌药物不存在交叉耐药性。利奈唑胺主要以原形药物经肾脏排泄。测得的血浆半衰期为4至5小时，所有适应证感染均允许每日给药两次。口服生物利用度几乎达100%，使得静脉剂型和口服剂型之间可按1:1转换。对照比较临床试验表明，利奈唑胺在治疗耐万古霉素屎肠球菌及耐甲氧西林金黄色葡萄球菌（MRSA）感染、医院获得性和社区获得性肺炎以及由易感菌引起的皮肤及皮肤结构感染方面有效。除单纯性皮肤及皮肤结构感染（每日两次，每次400mg）外，所有适应证的推荐剂量均为每日两次，每次600mg静脉注射或口服；轻度至中度肾或肝功能损害无需调整剂量。尚未观察到与单胺氧化酶抑制剂有临床意义的相互作用。少数患者中观察到可逆性骨髓抑制。利奈唑胺的革兰氏阳性菌活性与万古霉素相当，对多种感染有效，耐受性良好，腹泻、头痛和恶心是最常报告的不良反应。利奈唑胺为耐万古霉素屎肠球菌感染患者以及不能耐受万古霉素的MRSA感染患者提供了合理的治疗选择。
