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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
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 AT lixu synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance AT ganjunyuan synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance AT yiminwang synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance AT yunqiuqu synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance AT meijingzhou synergisticcombinationoftwoantimicrobialagentsclosingeachothersmutantselectionwindowstopreventantimicrobialresistance
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Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance

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