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替拉万星对多种耐药金黄色葡萄球菌的体外生物膜模型显示出优于万古霉素的活性。

Telavancin shows superior activity to vancomycin with multidrug-resistant Staphylococcus aureus in a range of in vitro biofilm models.

机构信息

Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, G4 0BA, Scotland, UK.

出版信息

Eur J Clin Microbiol Infect Dis. 2013 Oct;32(10):1327-32. doi: 10.1007/s10096-013-1883-z. Epub 2013 Apr 29.

DOI:10.1007/s10096-013-1883-z
PMID:23624635
Abstract

The activity of telavancin was compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in planktonic culture and biofilms grown using a range of in vitro models. Antibiotic efficacy was determined using 24 clinical isolates, including healthcare-associated (HA)-MRSA, community-associated (CA)-MRSA and isolates with reduced (intermediate) susceptibility to vancomycin (VISA). Activity against biofilms was compared using three models: 96-peg plates, 96-well flat-bottom plates and a flow-cell system. Cell death was evaluated using a metabolic dye and Live/Dead staining. The planktonic minimum inhibitory concentration (MIC) range for telavancin was lower than that for vancomycin (0.06-0.25 mg/l and 0.5-8 mg/l, respectively). Vancomycin (100 × MIC) killed, on average, 59% of cells in HA-MRSA biofilms grown on 96-peg plates, 44% of cells in CA-MRSA biofilms and 26% of cells in VISA biofilms. Telavancin (100 × MIC) killed, on average, 63%, 49% and 41% of cells, respectively. The antibiotics showed similar efficacy against MRSA biofilms but telavancin was more effective against those formed by VISA isolates. In the flow-cell system, antibiotic cell killing was enhanced with both antibiotics, killing up to 80% of biofilm-associated cells. The variance in cell killing displayed when biofilms were grown using different systems highlights the importance of selecting an appropriate model for antimicrobial efficacy tests. The flow-cell system more closely reflects conditions encountered during infection and is possibly more clinically relevant than a 96-well plate system. Despite differences between the models evaluated, telavancin typically demonstrated improved efficacy over vancomycin, indicating the potential value of the agent in the treatment of biofilm-mediated infections caused by S. aureus, especially multidrug-resistant isolates.

摘要

替考拉宁的活性与万古霉素在浮游培养物和生物膜中的活性进行了比较,使用一系列体外模型来研究耐甲氧西林金黄色葡萄球菌(MRSA)。使用 24 株临床分离株,包括医院获得性(HA)-MRSA、社区获得性(CA)-MRSA 和对万古霉素(VISA)中介度敏感的分离株,来确定抗生素的疗效。使用三种模型比较生物膜的活性:96 孔 PEG 板、96 孔平底板和流动池系统。使用代谢染料和 Live/Dead 染色评估细胞死亡。替考拉宁的浮游最低抑菌浓度(MIC)范围低于万古霉素(分别为 0.06-0.25 mg/L 和 0.5-8 mg/L)。万古霉素(100×MIC)平均杀死 HA-MRSA 生物膜上生长的 96 孔 PEG 板上的 59%的细胞、CA-MRSA 生物膜中的 44%的细胞和 VISA 生物膜中的 26%的细胞。替考拉宁(100×MIC)分别平均杀死 63%、49%和 41%的细胞。这两种抗生素对 MRSA 生物膜的疗效相似,但替考拉宁对 VISA 分离株形成的生物膜更有效。在流动池系统中,两种抗生素都增强了抗生素对细胞的杀伤作用,杀死了多达 80%的生物膜相关细胞。在使用不同系统生长的生物膜中显示出的细胞杀伤差异突出了为抗菌疗效测试选择合适模型的重要性。流动池系统更接近感染期间遇到的条件,并且可能比 96 孔板系统更具临床相关性。尽管评估的模型之间存在差异,但替考拉宁通常比万古霉素表现出更好的疗效,表明该药物在治疗金黄色葡萄球菌引起的生物膜介导感染方面具有潜在价值,尤其是多药耐药分离株。

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