Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Avenue Mounier 73 B1.73.05, 1200, Brussels, Belgium.
Drugs. 2015 Dec;75(18):2073-95. doi: 10.1007/s40265-015-0505-8.
Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Gram-positive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospital-acquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections.
奥利万星、替拉万星和达巴万星是最近上市的脂糖肽类抗生素，与传统药物相比具有显著差异。达巴万星主要通过抑制转糖基酶活性来抑制肽聚糖合成的晚期阶段，而奥利万星和替拉万星通过与二糖部分相连的亲脂性侧链锚定在细菌膜上，破坏膜的完整性并导致细菌溶解。奥利万星对万古霉素耐药肠球菌保持活性，对转肽酶的抑制作用强于转糖基酶。这些药物对革兰氏阳性菌具有很强的活性，特别是葡萄球菌（包括耐甲氧西林金黄色葡萄球菌和在一定程度上对万古霉素中介金黄色葡萄球菌）、链球菌（包括对多种药物耐药的肺炎球菌）和梭菌。所有药物均被批准用于治疗急性细菌性皮肤和皮肤结构感染，替拉万星还被批准用于治疗医院获得性和呼吸机相关性细菌性肺炎。替拉万星每天给药 10mg/kg，而奥利万星和达巴万星的半衰期显著延长，允许频繁给药（奥利万星单次剂量 1200mg，达巴万星第 1 天给予 1000mg，第 8 天给予 500mg），这在未来可能会用于门诊治疗。在临床开发过程中发现的可能存在的安全性问题包括：奥利万星增加了骨髓炎的风险；替拉万星有味觉障碍、肾毒性和校正的 QT 间期延长的风险（尤其是在存在高危共用药的情况下）；达巴万星会导致肝酶升高。奥利万星和替拉万星会干扰凝血试验。这些药物在临床试验中被证明与传统治疗相比不劣效，但在未来对更严重感染的评估中可能会更好地证明其优势。
