New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, 14260, USA.
Pharmacotherapy. 2010 Jan;30(1):80-94. doi: 10.1592/phco.30.1.80.
Resistance to antibiotics among gram-positive bacteria, especially enterococci and staphylococci, has led to the need to develop new antibiotics. Vancomycin, a glycopeptide antibiotic, has been used for over 3 decades to treat serious methicillin-resistant Staphylococcus aureus infections. The increased frequency of multidrug-resistant bacteria, especially vancomycin-resistant strains, has focused interest on three new lipoglycopeptides for the treatment of infections caused by gram-positive bacteria: oritavancin, dalbavancin, and telavancin. Although oritavancin and dalbavancin are still in development, telavancin received approval from the United States Food and Drug Administration in September 2009 for treatment of complicated skin and skin structure infections. Structurally different from vancomycin and teicoplanin, all three lipoglycopeptides have greater potency and less potential for development of resistant organisms. Of particular importance is the activity of oritavancin, dalbavancin, and telavancin against vancomycin-resistant organisms. In addition, the pharmacokinetic properties of these new antimicrobials substantially differ from those of vancomycin. Both oritavancin and dalbavancin have long terminal half-lives, which may allow for infrequent dosing. In addition, oritavancin is primarily cleared through hepatic pathways, which makes it potentially useful in patients with renal compromise. In animal models, these new lipoglycopeptides were effective in treating serious gram-positive infections, including complicated skin and skin structure infections, endocarditis, bacteremia, and pneumonia; in clinical studies, however, efficacy was shown only in complicated skin and skin structure infections for all three agents. According to preliminary data, the adverse-effect profile of these lipoglycopeptides is generally similar to that of drugs currently used to treat severe gram-positive infections. However, further evaluation and monitoring is necessary as more patients are exposed to these agents. As antimicrobial resistance continues to increase worldwide, the lipoglycopeptides may provide clinicians with a useful antimicrobial in the continued fight against multidrug-resistant gram-positive bacteria.
革兰氏阳性菌(尤其是肠球菌和葡萄球菌)对抗生素的耐药性导致了开发新抗生素的需求。万古霉素是一种糖肽类抗生素,已被使用超过 30 年,用于治疗严重的耐甲氧西林金黄色葡萄球菌感染。由于多药耐药菌(尤其是耐万古霉素的菌株)的发病率增加,人们对三种新型用于治疗革兰氏阳性菌感染的糖脂肽类抗生素(奥利万星、达巴万星和替考拉宁)产生了兴趣。虽然奥利万星和达巴万星仍在开发中,但替考拉宁已于 2009 年 9 月获得美国食品和药物管理局批准,用于治疗复杂的皮肤和皮肤结构感染。与万古霉素和替考拉宁在结构上不同,这三种糖脂肽类抗生素的抗菌活性更强,产生耐药菌的潜力更小。特别重要的是,奥利万星、达巴万星和替考拉宁对耐万古霉素菌具有活性。此外,这些新型抗菌药物的药代动力学特性与万古霉素有很大不同。奥利万星和达巴万星的半衰期均较长,这可能使它们的用药频率降低。此外,奥利万星主要通过肝脏途径清除,这使其在肾功能受损的患者中可能具有潜在的应用价值。在动物模型中,这些新型糖脂肽类抗生素在治疗严重的革兰氏阳性感染方面(包括复杂的皮肤和皮肤结构感染、心内膜炎、菌血症和肺炎)是有效的;然而,在临床试验中,只有三种药物中的替考拉宁在复杂的皮肤和皮肤结构感染中显示出疗效。根据初步数据,这些糖脂肽类抗生素的不良反应谱与目前用于治疗严重革兰氏阳性感染的药物大致相似。然而,随着更多的患者接触这些药物,还需要进一步评估和监测。随着全球范围内抗生素耐药性的不断增加,糖脂肽类抗生素可能为临床医生在与多药耐药革兰氏阳性菌的持续斗争中提供一种有用的抗菌药物。