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  • 标题:Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
  • 本地全文:下载
  • 作者:Xuejie Xu ; Li Xu ; Ganjun Yuan
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2018
  • 卷号:8
  • 期号:1
  • 页码:7237
  • DOI:10.1038/s41598-018-25714-z
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:s) and mutant prevention concentrations (MPCs) alone or in combinations including different proportions were first determined using agar plates. The results indicated that different proportions of a combination had presented different MPCs and mutant selection window (MSWs), and also showed that the smaller the FICIs of two agents in combinations were, the more probable their MSWs were to close each other. As two agents of a combination had different pharmacokinetic characters, the ratios of two agents in blood and infectious sites were likely different even though a specific proportion was administrated, which would lead to different effects preventing resistance. Thereby, these experimental results theoretically indicated that synergistic combination closing each other's MSWs had a great potency to prevent resistance according to the hypotheses of MSW and MPC, and deduced that in vivo synergistic validity of a combination was likely a key to prevent resistance. Moreover, a synergistic combination of roxithromycin/doxycycline with the FICIs of 0.26-0.50 and 0.28-0.38 respectively against MRSA 01 and 02 was obtained, and the MSWs of these two agents could be simultaneously closed each other in a certain range of proportions, but for others. Meanwhile, its effect preventing resistance needs to be further verified.
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