Fung H B, Kirschenbaum H L, Ojofeitimi B O
Critical Care Center, Veterans Affairs Medical Center, Bronx, New York 10468, USA.
Clin Ther. 2001 Mar;23(3):356-91. doi: 10.1016/s0149-2918(01)80043-6.
Linezolid is the first oxazolidinone anti-infective agent marketed in the United States. It is indicated for the treatment of nosocomial pneumonia, complicated skin and skin-structure infections caused by methicillin-sensitive or methicillin-resistant Staphylococcus aureus and other susceptible organisms, and vancomycin-resistant Enterococcus faecium infections. It also is indicated for the treatment of uncomplicated skin and skin-structure infections caused by methicillin-sensitive S. aureus or Streptococcus pyogenes, and community-acquired pneumonia caused by penicillin-sensitive Streptococcus pneumoniae.
This article reviews the pharmacologic properties and clinical usefulness of linezolid.
Using the terms linezolid, PNU-100766, and oxazolidinone, we performed a literature search of the following databases: MEDLINE (1966 to September 2000), HealthSTAR (1993 to September 2000), Iowa Drug Information Service (1966 to September 2000), International Pharmaceutical Abstracts (1970 to September 2000), PharmaProjects (January 2000 version), and meeting abstracts of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1996 to 2000).
Linezolid has a unique structure and mechanism of action, which targets protein synthesis at an exceedingly early stage. Consequently, cross-resistance with other commercially available antimicrobial agents is unlikely. It is primarily effective against gram-positive bacteria. To date, resistance to linezolid has been reported in patients infected with enterococci. The pharmacokinetic parameters of linezolid in adults are not altered by hepatic or renal function, age, or sex to an extent requiring dose adjustment. Linezolid is metabolized via morpholine ring oxidation, which is independent of the cytochrome P450 (CYP450) enzyme system; as a result, linezolid is unlikely to interact with medications that stimulate or inhibit CYP450 enzymes. Compassionate-use trials and other clinical studies involving mainly adult hospitalized patients with gram-positive infections have shown that linezolid administered intravenously or orally is effective in a variety of nosocomial and community-acquired infections, including those caused by resistant gram-positive organisms. Reported adverse effects include thrombocytopenia. diarrhea, headache, nausea, vomiting, insomnia, constipation, rash, and dizziness. Preliminary pharmacoeconomic data indicate that a significantly higher percentage of patients receiving linezolid therapy versus comparator could be discharged from the hospital by day 7 (P = 0.005).
Linezolid appears to be effective while maintaining an acceptable tolerability profile. Due to the risk of bacterial resistance, linezolid should be reserved for the treatment of documented serious vancomycin-resistant enterococcal infections.
利奈唑胺是美国上市的首个恶唑烷酮类抗感染药物。它适用于治疗医院获得性肺炎、由对甲氧西林敏感或耐药的金黄色葡萄球菌及其他易感菌引起的复杂性皮肤及皮肤结构感染，以及耐万古霉素屎肠球菌感染。它还适用于治疗由对甲氧西林敏感的金黄色葡萄球菌或化脓性链球菌引起的非复杂性皮肤及皮肤结构感染，以及由对青霉素敏感的肺炎链球菌引起的社区获得性肺炎。
本文综述利奈唑胺的药理特性及临床应用价值。
使用利奈唑胺、PNU - 100766和恶唑烷酮等术语，我们检索了以下数据库：医学索引数据库（1966年至2000年9月）、健康之星数据库（1993年至2000年9月）、爱荷华州药物信息服务数据库（1966年至2000年9月）、国际药学文摘数据库（1970年至2000年9月）、药物研发项目数据库（2000年1月版），以及美国传染病学会和抗菌药物与化疗跨学科会议的会议摘要（1996年至2000年）。
利奈唑胺具有独特的结构和作用机制，它在极早期阶段靶向蛋白质合成。因此，与其他市售抗菌药物发生交叉耐药的可能性不大。它主要对革兰氏阳性菌有效。迄今为止，已报道在感染肠球菌的患者中出现了对利奈唑胺的耐药性。利奈唑胺在成年人中的药代动力学参数不会因肝功能、肾功能、年龄或性别而改变到需要调整剂量的程度。利奈唑胺通过吗啉环氧化进行代谢，这独立于细胞色素P450（CYP450）酶系统；因此，利奈唑胺不太可能与刺激或抑制CYP450酶的药物发生相互作用。同情用药试验及其他主要涉及成年住院革兰氏阳性菌感染患者的临床研究表明，静脉或口服给予利奈唑胺对多种医院获得性和社区获得性感染有效，包括由耐药革兰氏阳性菌引起的感染。报道的不良反应包括血小板减少、腹泻、头痛、恶心、呕吐、失眠、便秘、皮疹和头晕。初步的药物经济学数据表明，与对照药物相比，接受利奈唑胺治疗的患者在第7天出院的比例显著更高（P = 0.005）。
利奈唑胺似乎有效且耐受性可接受。由于存在细菌耐药的风险，利奈唑胺应仅用于治疗已确诊的严重耐万古霉素肠球菌感染。
