Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections.
Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections.
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DOI：
10.2147/dddt.s30728
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Grau S
中科院分区：
文献类型：
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作者：
Urbina O;Ferrández O;Espona M;Salas E;Ferrández I;Grau S
磷酸替地唑胺（TR-701）是替地唑胺（TR-700）的前药，是下一代恶唑烷酮，在其第一个III期临床试验中显示出治疗急性细菌性皮肤和皮肤结构感染的良好结果。当口服或静脉内给药时，泰地唑胺具有高生物利用度、渗透性和组织分布。对葡萄球菌属菌株，链球菌属，和肠球菌属（Enterococcus spp.）体外研究，包括对利奈唑胺耐药的菌株和对万古霉素或达托霉素不敏感的菌株。其药代动力学特征允许每日一次给药，导致比利奈唑胺更可预测的疗效和安全性特征。在替地唑胺给药长达3周的I期、II期或III期临床试验中，当以200 mg的治疗剂量使用时，未报告与替地唑胺相关的血液学不良反应。鉴于200、300和400 mg剂量的临床和微生物学疗效相似，选择200 mg每日一次持续6天的最低有效剂量用于急性细菌性皮肤和皮肤结构感染的III期研究，提供了一种安全的给药方案，发生骨髓抑制的可能性较低。与利奈唑胺不同，替地唑胺在体内不会抑制单胺氧化酶，因此预期不会与肾上腺素能、多巴胺能和多巴胺能药物发生相互作用。总之，泰地唑胺是一种新型抗生素，对引起皮肤和软组织感染的革兰氏阳性微生物（包括对万古霉素、利奈唑胺和达托霉素耐药的菌株）具有强效活性，因此满足了日益增长的治疗需求。
Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. Its pharmacokinetic characteristics allow for a once-daily administration that leads to a more predictable efficacy and safety profile than those of linezolid. No hematological adverse effects have been reported associated with tedizolid when used at the therapeutic dose of 200 mg in Phase I, II, or III clinical trials of up to 3 weeks of tedizolid administration. Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need.