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万古霉素联合达托霉素对耐万古霉素肠球菌的协同作用。

Synergistic Effect of Vancomycin Combined with Daptomycin Against Vancomycin-Resistant Enterococci.

机构信息

Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

出版信息

Microb Drug Resist. 2019 Dec;25(10):1484-1489. doi: 10.1089/mdr.2019.0033. Epub 2019 Jul 25.

Abstract

New antimicrobial agents are being designed to treat infections of multidrug-resistant pathogens and have been introduced in the past few years, but there has been a worldwide increase in the incidence of vancomycin-resistant enterococci (VRE) infections, and treatment options are still limited. In this study, it was aimed to investigate the activity of vancomycin combined with daptomycin against 30 VRE strains. The minimum inhibitory concentration (MIC) values of antibiotics were determined using broth microdilution assay as described by the Clinical and Laboratory Standards Institute (CLSI). The activities of antibiotics in combination were assessed using a broth microcheckerboard method. In addition, 4 of the 30 strains were randomly selected to determine the time-kill curves at 1 × MIC concentrations and 2 of 4 strains at ½ × MIC concentrations. Viable counts were determined at 0-, 4-, 8-, 12-, 24-, 48-, and 72-hr intervals. This was accomplished by subculturing 0.1 mL from repetitive serial dilutions in Eppendorf tubes, followed by subculturing 0.1 mL from tubes onto Tryptic Soy Agar plates. All plates were incubated at 35°C for 24 hr. The synergistic effect was found 100% using the broth microcheckerboard method, and in strains tested using the time-kill method at both 1 × MIC and ½ × MIC concentrations. The results of this study suggest that this combination could be effective in the treatment of the VRE-associated infection.

摘要

新型抗菌药物被设计用于治疗多药耐药病原体感染,并在过去几年中得到了应用,但万古霉素耐药肠球菌(VRE)感染的全球发病率仍在上升,治疗选择仍然有限。本研究旨在研究万古霉素联合达托霉素对 30 株 VRE 菌株的活性。采用肉汤微量稀释法(CLSI 描述)测定抗生素的最低抑菌浓度(MIC)值。采用肉汤微量棋盘法评估抗生素联合的活性。此外,随机选择 30 株中的 4 株,在 1×MIC 浓度和 4 株中的 2 株在 ½×MIC 浓度下确定时间杀伤曲线。在 0、4、8、12、24、48 和 72 小时的时间间隔测定活菌数。通过在 Eppendorf 管中进行重复连续稀释,从管中取出 0.1 mL 进行亚培养,然后从管中取出 0.1 mL 进行接种到大豆胰蛋白胨琼脂板上,来完成这一过程。所有平板在 35°C 孵育 24 小时。采用肉汤微量棋盘法发现协同作用为 100%,在 1×MIC 和 ½×MIC 浓度下采用时间杀伤法测试的菌株中也发现协同作用为 100%。本研究结果表明,该联合用药可能对治疗 VRE 相关感染有效。

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