Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance

Abstract Antimicrobial resistance seriously threatened human health. Combination therapy is generally an effective strategy to fight resistance, while some data on its effects are conflicting. To explore the reasons, the fractional inhibitory concentration indexes (FICIs) of three designed combinati...

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Autores principales: Xuejie Xu, Li Xu, Ganjun Yuan, Yimin Wang, Yunqiu Qu, Meijing Zhou
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/63965a28105a42c4bd82ce20538a6a18
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spelling oai:doaj.org-article:63965a28105a42c4bd82ce20538a6a182021-12-02T15:07:52ZSynergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance10.1038/s41598-018-25714-z2045-2322https://doaj.org/article/63965a28105a42c4bd82ce20538a6a182018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25714-zhttps://doaj.org/toc/2045-2322Abstract Antimicrobial resistance seriously threatened human health. Combination therapy is generally an effective strategy to fight resistance, while some data on its effects are conflicting. To explore the reasons, the fractional inhibitory concentration indexes (FICIs) of three designed combinations against methicillin-resistant Staphylococcus aureus (MRSA) were determined using checkerboard method, and their minimal concentrations inhibiting colony formation by 99% (MIC99%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.Xuejie XuLi XuGanjun YuanYimin WangYunqiu QuMeijing ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-7 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Xuejie Xu
Li Xu
Ganjun Yuan
Yimin Wang
Yunqiu Qu
Meijing Zhou
Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
description Abstract Antimicrobial resistance seriously threatened human health. Combination therapy is generally an effective strategy to fight resistance, while some data on its effects are conflicting. To explore the reasons, the fractional inhibitory concentration indexes (FICIs) of three designed combinations against methicillin-resistant Staphylococcus aureus (MRSA) were determined using checkerboard method, and their minimal concentrations inhibiting colony formation by 99% (MIC99%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.
format article
author Xuejie Xu
Li Xu
Ganjun Yuan
Yimin Wang
Yunqiu Qu
Meijing Zhou
author_facet Xuejie Xu
Li Xu
Ganjun Yuan
Yimin Wang
Yunqiu Qu
Meijing Zhou
author_sort Xuejie Xu
title Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
title_short Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
title_full Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
title_fullStr Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
title_full_unstemmed Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
title_sort synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/63965a28105a42c4bd82ce20538a6a18
work_keys_str_mv AT xuejiexu synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance
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AT ganjunyuan synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance
AT yiminwang synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance
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