Goldstein Beth P, Jones Ronald N, Fritsche Thomas R, Biedenbach Douglas J
Vicuron Pharmaceuticals, King of Prussia, PA, USA.
Diagn Microbiol Infect Dis. 2006 Feb;54(2):83-7. doi: 10.1016/j.diagmicrobio.2005.09.004.
Dalbavancin, a new-generation semisynthetic lipoglycopeptide in phase 3 clinical development, has been documented to be more active than vancomycin or teicoplanin against Gram-positive bacteria, including multidrug-resistant strains, by in vitro testing and in animal models. The human pharmacokinetics of dalbavancin predicts efficacy at weekly dosing intervals. In a phase 2 open-label clinical trial, dalbavancin exhibited superiority when compared with vancomycin against catheter-related bloodstream infection (CR-BSI). The majority of pathogens identified in this study as in clinical practice were coagulase-negative staphylococci (CoNS), necessitating rigorous characterization of duplicate isolates to rule out contaminants and to validate cases for study evaluations. At follow-up for the intent-to-treat population, overall pathogen eradication was 92.3% for dalbavancin and 75.9% for vancomycin. We describe the details of organisms isolated, their epidemiologic/genetic characterization, susceptibility patterns against glycopeptides, and the eradication rates by organism group. In conclusion, dalbavancin was active against all isolated pathogens associated with CR-BSI (CoNS, Staphylococcus aureus and Enterococcus faecalis; all MIC results, < or = 0.25 microg/mL) and achieved significant (P < 0.05) clinical success when compared with vancomycin.
达巴万星是一种处于3期临床开发阶段的新一代半合成脂糖肽，体外试验和动物模型研究表明，其对革兰氏阳性菌（包括多重耐药菌株）的活性比万古霉素或替考拉宁更强。达巴万星的人体药代动力学表明，每周给药一次即可达到有效剂量。在一项2期开放标签临床试验中，与万古霉素相比，达巴万星在治疗导管相关血流感染（CR-BSI）方面表现出优势。本研究中鉴定出的大多数病原体与临床实践中一样，为凝固酶阴性葡萄球菌（CoNS），因此有必要对重复分离株进行严格鉴定，以排除污染物，并确认用于研究评估的病例。在意向性治疗人群的随访中，达巴万星的总体病原体清除率为92.3%，万古霉素为75.9%。我们描述了分离出的微生物的详细情况、它们的流行病学/基因特征、对糖肽类的敏感性模式以及各微生物组的清除率。总之，达巴万星对所有与CR-BSI相关的分离病原体（CoNS、金黄色葡萄球菌和粪肠球菌；所有MIC结果均≤0.25μg/mL）均有活性，与万古霉素相比，取得了显著（P<0.05）的临床成功。
