Dalbavancin: A Novel Lipoglycopeptide Antibiotic with Extended Activity Against Gram-Positive Infections.
Dalbavancin: A Novel Lipoglycopeptide Antibiotic with Extended Activity Against Gram-Positive Infections.
复制标题
DOI：
10.1007/s40121-015-0077-7
复制
发表时间：
2015-09
影响因子：
5.4
通讯作者：
Rybak MJ
中科院分区：
文献类型：
--
作者：
Smith JR;Roberts KD;Rybak MJ
达巴万星是一种脂糖肽抗生素，最近被美国食品和药物管理局（FDA）批准用于急性细菌性皮肤和皮肤结构感染（ABSSSI）。它对革兰氏阳性病原体有活性，包括耐甲氧西林金黄色葡萄球菌（MRSA），最低抑菌浓度（MIC）始终<0.125 µg/ml，远低于大多数其他抗MRSA药物。达巴万星具有超过1周的延长半衰期，允许初始剂量为1000 mg，1周后为500 mg，以完成ABSSSI的疗程。它约95%与蛋白结合，广泛分布于全身，在许多组织中达到与血浆水平相似的浓度。针对MRSA，达巴霉素在体外的效力是万古霉素的4-8倍，并且有限的数据表明其具有针对MRSA的活性，而对万古霉素如hVISA和VISA的敏感性降低。达巴霉素还具有抗链球菌和肠球菌的体外活性，尽管缺乏抗万古霉素耐药肠球菌的活性。在3期ABSSSI研究中，达巴霉素显示出与万古霉素相似的活性，并提供了更方便的给药方案。有限的2期数据表明达巴霉素在导管相关的血流感染中也具有活性。潜在的进一步治疗用途包括需要长期治疗的疾病，如骨髓炎和感染性心内膜炎，尽管目前缺乏数据。达巴霉素的半衰期延长，沿着其对革兰氏阳性生物体的体外活性，对其他抗MRSA抗生素的敏感性降低，表明它可能具有令人兴奋的临床作用。
Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) for acute bacterial skin and skin structure infections (ABSSSIs). It is active against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), and minimum inhibitory concentrations (MICs) are consistently <0.125 µg/ml, much lower than most other anti-MRSA agents. Dalbavancin possesses an extended half-life of over 1 week, allowing an initial dose of 1000 mg followed by 500 mg 1 week later to complete a course of therapy for ABSSSI. It is approximately 95% protein bound and is widely distributed throughout the body, achieving concentrations similar to plasma levels in numerous tissues. Against MRSA, dalbavancin is 4–8 times more potent than vancomycin in vitro, and limited data suggest it possesses activity against MRSA with reduced susceptibility to vancomycin such as hVISA and VISA. Dalbavancin also possesses in vitro activity against streptococci and enterococci, although activity against vancomycin-resistant enterococci is lacking. In phase 3 ABSSSI studies, dalbavancin demonstrated similar activity to vancomycin and provides a more convenient dosing regimen. Limited phase 2 data suggest dalbavancin also possesses activity in catheter-related bloodstream infections. Potential further therapeutic uses include conditions that require long-term treatment such as osteomyelitis and infective endocarditis, although data are currently lacking. The extended half-life of dalbavancin, along with its in vitro activity against gram-positive organisms with reduced susceptibility to other anti-MRSA antibiotics, suggest it could have an exciting clinical role going forward.