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DOI10.1073/PNAS.2023467118
Comparing treatment strategies to reduce antibiotic resistance in an in vitro epidemiological setting
Angst D.C.; Tepekule B.; Sun L.; Bogos B.; Bonhoeffer S.
发表日期2021
ISSN00278424
卷号118期号:13
英文摘要The rapid rise of antibiotic resistance, combined with the increasing cost and difficulties to develop new antibiotics, calls for treatment strategies that enable more sustainable antibiotic use. The development of such strategies, however, is impeded by the lack of suitable experimental approaches that allow testing their effects under realistic epidemiological conditions. Here, we present an approach to compare the effect of alternative multidrug treatment strategies in vitro using a robotic liquid-handling platform. We use this framework to study resistance evolution and spread implementing epidemiological population dynamics for treatment, transmission, and patient admission and discharge, as may be observed in hospitals. We perform massively parallel experimental evolution over up to 40 d and complement this with a computational model to infer the underlying population-dynamical parameters. We find that in our study, combination therapy outperforms monotherapies, as well as cycling and mixing, in minimizing resistance evolution and maximizing uninfecteds, as long as there is no influx of double resistance into the focal treated community. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Antibiotic resistance; Combination therapy; Experimental epidemiology
语种英语
scopus关键词adult; antibiotic resistance; article; computer model; drug combination; hospital admission; human; in vitro study; monotherapy; population dynamics
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180051
作者单位Institute of Integrative Biology, Department for Environmental System Science, ETH Zurich, Zurich, 8092, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, 8091, Switzerland; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, United States; Redbiotec AG, Schlieren, 8952, Switzerland
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GB/T 7714
Angst D.C.,Tepekule B.,Sun L.,et al. Comparing treatment strategies to reduce antibiotic resistance in an in vitro epidemiological setting[J],2021,118(13).
APA Angst D.C.,Tepekule B.,Sun L.,Bogos B.,&Bonhoeffer S..(2021).Comparing treatment strategies to reduce antibiotic resistance in an in vitro epidemiological setting.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA Angst D.C.,et al."Comparing treatment strategies to reduce antibiotic resistance in an in vitro epidemiological setting".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).
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