Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain.
Int J Antimicrob Agents. 2010 Nov;36(5):401-7. doi: 10.1016/j.ijantimicag.2010.06.048. Epub 2010 Aug 21.
Oritavancin is a lipoglycopeptide antibiotic under investigation for the treatment of serious infections caused by Gram-positive bacteria. Oritavancin has demonstrated rapid dose-dependent bactericidal activity towards vancomycin-susceptible and -resistant enterococci, meticillin-susceptible and -resistant Staphylococcus aureus, vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), vancomycin-resistant S. aureus (VRSA) and small-colony variants of S. aureus. It is also active against Clostridium difficile. Upon intravenous administration, oritavancin displays a three-compartment pharmacokinetic model, dose proportionality, a distribution volume of ca. 110 L, a terminal elimination half-life in excess of 2 weeks and it is not metabolised. Its pharmacodynamic properties make it an ideal antibiotic for a once-daily or even single-dose regimen. Oritavancin is currently under review by the US Food and Drug Administration. So far, oritavancin has demonstrated efficacy in two pivotal Phase III trials conducted in patients with complicated skin and skin-structure infections in which oritavancin was compared with vancomycin plus cefalexin. In both trials, the primary endpoint (clinical cure in clinically evaluable patients at first follow-up with a 10% non-inferiority margin) was met, with the advantages of shorter duration of therapy and fewer adverse events. Further results indicating its activity against bacteria growing in biofilms as well as stationary-phase bacteria open the way for its use to treat prosthetic device infections, which is to be investigated in upcoming trials.
奥利万星是一种正在研究用于治疗革兰氏阳性菌引起的严重感染的糖肽类抗生素。奥利万星对万古霉素敏感和耐药肠球菌、甲氧西林敏感和耐药金黄色葡萄球菌、万古霉素中介金黄色葡萄球菌（VISA）、异质性万古霉素耐药金黄色葡萄球菌（hVISA）、万古霉素耐药金黄色葡萄球菌（VRSA）和金黄色葡萄球菌小菌落变异体具有快速、剂量依赖性杀菌活性。它对艰难梭菌也有活性。静脉注射给药时，奥利万星表现出三房室药代动力学模型、剂量比例性、约 110 L 的分布容积、超过 2 周的终末消除半衰期，且不被代谢。其药效学特性使其成为每日一次甚至单剂量方案的理想抗生素。奥利万星目前正在接受美国食品和药物管理局的审查。到目前为止，奥利万星已在两项关键性 III 期临床试验中证明了疗效，这些试验在患有复杂性皮肤和皮肤结构感染的患者中进行，将奥利万星与万古霉素加头孢氨苄进行了比较。在这两项试验中，主要终点（首次随访时具有 10%非劣效性边界的临床可评估患者的临床治愈率）得到满足，具有治疗持续时间更短和不良反应更少的优势。进一步表明其对生物膜中生长的细菌和静止期细菌具有活性的结果为其用于治疗假体装置感染开辟了道路，这将在即将进行的试验中进行研究。
