Das Biswadeep, Sarkar Chayna, Das Debasmita, Gupta Amit, Kalra Arnav, Sahni Shubham
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS) Rishikesh, Rishikesh, India.
Department of Pharmacology & Clinical Pharmacology, North Eastern Indira Gandhi Regional Institute of Health & Medical Sciences (NEIGRIHMS) Shillong, Shillong, India.
Ther Adv Infect Dis. 2017 Mar;4(2):49-73. doi: 10.1177/2049936117690501. Epub 2017 Mar 8.
Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA ( group, or ). Telavancin has two proposed mechanisms of action. , telavancin has a rapid, concentration-dependent bactericidal effect, due to disruption of cell membrane integrity. Telavancin has demonstrable activity against aerobic and anaerobic Gram-positive bacteria. Telavancin and vancomycin have similar spectra of activity. Gram-negative bacteria are usually non-susceptible to telavancin. Telavancin has been successfully tested in various animal models of bacteremia, endocarditis, meningitis, and pneumonia. Phase II Telavancin versus Standard Therapy for Treatment of Complicated Skin and Soft-Tissue Infections due to Gram-Positive Bacteria (FAST 1 and FAST 2) and phase III [Assessment of Telavancin in Complicated Skin and Skin Structure Infections 1 (ATLAS 1 and ATLAS 2)] clinical trials have been conducted for evaluating telavancin's efficacy and safety in cSSSIs. Phase III clinical trials have been carried out for evaluating telavancin's safety and efficacy in nosocomial pneumonia [Assessment of Telavancin for Treatment of Hospital acquired Pneumonia 1 and 2 (ATTAIN 1 and ATTAIN 2)]. A phase II randomized, double-blind, clinical trial has been carried out for evaluating telavancin's safety and efficacy in uncomplicated bacteremia [Telavancin for Treatment of Uncomplicated Bacteremia (ASSURE)]. Pacemaker lead-related infective endocarditis due to a vancomycin intermediate (VISA) strain (non-daptomycin susceptible) was successfully treated with parenteral telavancin for 8 weeks. Telavancin extensively binds to serum albumin (~93%) and has a relatively small volume of distribution. Telavancin is not biotransformed by any cytochrome P microsomal enzymes and excreted mainly in the urine. Though well-tolerated, worrisome adverse effects, including renal dysfunction and QTc prolongation are of potential concern. Given its extensive binding to plasma proteins, long half-life, and a long post-antibiotic effect, it represents a promising addition to the therapeutic armamentarium in combating infections caused by resistant Gram-positive pathogens, namely, MRSA.
特拉万星（TD-6424）是一种半合成脂糖肽类万古霉素衍生物，是Theravance公司研发的一种新型抗菌药物，用于克服革兰氏阳性菌感染，特别是耐甲氧西林金黄色葡萄球菌（MRSA）感染。美国食品药品监督管理局（USFDA）于2009年批准特拉万星用于治疗由革兰氏阳性菌引起的复杂性皮肤及皮肤结构感染（cSSSIs），包括MRSA（ 组或 组）。特拉万星有两种作用机制。其一，由于细胞膜完整性遭到破坏，特拉万星具有快速的浓度依赖性杀菌作用。特拉万星对需氧和厌氧革兰氏阳性菌均有显著活性。特拉万星和万古霉素的活性谱相似。革兰氏阴性菌通常对特拉万星不敏感。特拉万星已在菌血症、心内膜炎、脑膜炎和肺炎等多种动物模型中成功进行了测试。开展了II期试验（特拉万星与标准疗法治疗革兰氏阳性菌引起的复杂性皮肤和软组织感染（FAST 1和FAST 2））以及III期试验[评估特拉万星在复杂性皮肤及皮肤结构感染中的疗效1（ATLAS 1和ATLAS 2）]以评估特拉万星在cSSSIs中的疗效和安全性。开展了III期临床试验以评估特拉万星在医院获得性肺炎中的安全性和疗效[评估特拉万星治疗医院获得性肺炎1和2（ATTAIN 1和ATTAIN 2）]。开展了一项II期随机、双盲临床试验以评估特拉万星在非复杂性菌血症中的安全性和疗效[特拉万星治疗非复杂性菌血症（ASSURE）]。一株万古霉素中介（VISA）菌株（对达托霉素不敏感）引起的心内膜炎起搏器导线相关感染，经静脉注射特拉万星治疗8周后成功治愈。特拉万星与血清白蛋白广泛结合（约93%），分布容积相对较小。特拉万星不会被任何细胞色素P微粒体酶代谢，主要经尿液排泄。尽管耐受性良好，但令人担忧的不良反应，包括肾功能不全和QTc延长仍值得关注。鉴于其与血浆蛋白广泛结合、半衰期长以及抗生素后效应长，它有望成为对抗耐药革兰氏阳性病原体（即MRSA）所致感染的治疗药物库中的新成员。
