Comparative activity of the new lipoglycopeptide telavancin in the presence and absence of serum against 50 glycopeptide non-susceptible staphylococci and three vancomycin-resistant Staphylococcus aureus
Comparative activity of the new lipoglycopeptide telavancin in the presence and absence of serum against 50 glycopeptide non-susceptible staphylococci and three vancomycin-resistant Staphylococcus aureus
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DOI：
10.1093/jac/dkl235
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发表时间：
2006-08-01
影响因子：
5.2
通讯作者：
Rybak, Michael J.
中科院分区：
文献类型：
--
作者：
Leuthner, Kimberly D.;Cheung, Chrissy M.;Rybak, Michael J.
背景。特拉万星是一种新型多功能脂糖肽抗生素，对多种病原体表现出广谱革兰氏阳性活性。我们与万古霉素、奎努普丁/达福普丁、利奈唑胺和 方法：针对所有抗菌药物进行 MIC 和 MBC。使用两种 GISS 菌株（Mu50；NJ992）和 VRSA（VRSA(MI)；VRSA(PA)）在 1、2、4、8、16 和 32x MIC 下进行时间灭活实验。在存在和不存在血清的情况下评估特拉万星和达托霉素。结果：所有 GISS 和 hGISS 对测试药物均敏感，其中特拉万星和奎努普丁/达福普汀表现出最低 MIC，其次是达托霉素、利奈唑胺和万古霉素。针对 VRSA，达托霉素和奎努普丁/达福普汀的 MIC 最低，其次是利奈唑胺、特拉万星和万古霉素。在血清存在下，特拉万星和达托霉素 MIC 增加 1 至 4 倍。在存在和不存在血清的情况下，特拉万星和达托霉素证明了浓度依赖性活性。特拉万星和达托霉素对 GISS 具有杀菌作用，并且在血清存在下表现相似。奎奴普汀/达福普汀在临床可达到的浓度下表现出杀菌活性，而利奈唑胺具有抑菌作用。 结论：特拉万星在等于或高于 4 倍 MIC 的浓度下对 GISS、hGISS 和 VRSA 表现出浓度依赖性杀菌活性，该浓度对应于 GISS 的治疗水平和针对 VRSA 的临床达到浓度。与达托霉素相似，特拉万星活性在血清存在下减弱，但杀菌活性得以维持。有必要对特拉万星针对 GISS、hGISS 和 VRSA 进行进一步研究。
Background. Telavancin, a new multifunctional lipoglycopeptide antibiotic, exhibits broad-spectrum Gram-positive activity against a variety of pathogens. We examined the effects of human serum and antimicrobial concentrations on the activity of telavancin against glycopeptide-intermediate staphylococcal species (GISS), heteroresistant GISS (hGISS) and three vancomycin-resistant Staphylococcus aureus (VRSA) compared with vancomycin, quinupristin/dalfopristin, linezolid and daptomycin.Methods: MIC and MBCs were performed against all antimicrobials. Time-kill experiments were performed using two strains of GISS (Mu50; NJ992) and VRSA (VRSA(MI); VRSA(PA)) at 1, 2,4,8,16 and 32x MIC. Telavancin and daptomycin were evaluated in the presence and absence of serum.Results: All GISS and hGISS were susceptible to the tested agents with telavancin and quinupristin/dalfopristin demonstrating the lowest MIC, followed by daptomycin, linezolid and vancomycin. Against VRSA, daptomycin and quinupristin/dalfopristin had the lowest MIC, followed by linezolid, telavancin and vancomycin. In the presence of serum, telavancin and daptomycin MICs increased 1- to 4-fold. Concentration-dependent activity was demonstrated by telavancin and daptomycin, in the presence and absence of serum. Telavancin and daptomycin were bactericidal against GISS and performed similarly in the presence of serum. Quinupristin/dalfopristin demonstrated bactericidal activity at clinically achievable concentrations, whereas linezolid was bacteriostatic.Conclusions: Telavancin demonstrated concentration-dependent bactericidal activity against GISS, hGISS and VRSA at concentrations equal to or above 4x MIC, which corresponds to therapeutic levels against GISS and clinically achieved concentrations against the VRSA. Similar to daptomycin, telavancin activity was diminished in the presence of serum but bactericidal activity was maintained. Further investigation with telavancin against GISS, hGISS and VRSA is warranted.