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双管齐下对抗致病菌:噬菌体与抗生素联合策略。

Fighting Pathogenic Bacteria on Two Fronts: Phages and Antibiotics as Combined Strategy.

机构信息

Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany.

Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

出版信息

Front Cell Infect Microbiol. 2019 Feb 18;9:22. doi: 10.3389/fcimb.2019.00022. eCollection 2019.

Abstract

With the emerging threat of infections caused by multidrug resistant bacteria, phages have been reconsidered as an alternative for treating infections caused by tenacious pathogens. However, instead of replacing antibiotics, the combination of both types of antimicrobials can be superior over the use of single agents. Enhanced bacterial suppression, more efficient penetration into biofilms, and lowered chances for the emergence of phage resistance are the likely advantages of the combined strategy. While a number of studies have provided experimental evidence in support of this concept, negative interference between phages and antibiotics have been reported as well. Neutral effects have also been observed, but in those cases, combined approaches may still be important for at least hampering the development of resistance. In any case, the choice of phage type and antibiotic as well as their mixing ratios must be given careful consideration when deciding for a dual antibacterial approach. The most frequently tested bacterium for a combined antibacterial treatment has been , but encouraging results have also been reported for , and . Given the immense play area of conceivable phage-antibiotic combinations and their potential excess value, it is time to recapitulate of what has been achieved so far. This review therefore gathers and compares the results from most relevant studies in order to help researchers and clinicians in their strategies to combat multidrug resistant bacteria. Special attention is given to the selected bacterial model organisms, the phage families and genera employed, and the experimental design and evaluation (e.g., vs. models, biofilm vs. planktonic culture experiments, order and frequency of administration etc.). The presented data may serve as a framework for directed further experimental approaches to ultimately achieve a resolute challenge of multidrug resistant bacteria based on traditional antibiotics and phages.

摘要

随着多药耐药菌感染威胁的出现,噬菌体已被重新考虑作为治疗顽固病原体感染的替代方法。然而,这种联合治疗策略并不是替代抗生素,而是将这两种类型的抗菌药物联合使用可能优于单一药物的使用。增强细菌抑制、更有效地渗透生物膜以及降低噬菌体产生耐药性的机会是这种联合策略的可能优势。虽然许多研究已经提供了支持这一概念的实验证据,但也有报道称噬菌体和抗生素之间存在负干扰。中性效应也观察到了,但在这些情况下,联合方法对于至少阻碍耐药性的发展仍然很重要。在任何情况下,在决定采用双重抗菌方法时,必须仔细考虑噬菌体类型和抗生素的选择以及它们的混合比例。最常被用于联合抗菌治疗的细菌是 ,但也有报道称 和 也取得了令人鼓舞的结果。鉴于可想象的噬菌体-抗生素组合的巨大作用范围及其潜在的额外价值,现在是回顾迄今为止所取得的成果的时候了。因此,本综述收集并比较了大多数相关研究的结果,以帮助研究人员和临床医生制定对抗多药耐药菌的策略。特别关注选定的细菌模式生物、使用的噬菌体科和属,以及实验设计和评估(例如, 与 模型、生物膜与浮游培养实验、给药顺序和频率等)。所呈现的数据可以作为进一步实验方法的框架,最终实现基于传统抗生素和噬菌体的多药耐药菌的坚决挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fea/6387922/e7e774aea5c2/fcimb-09-00022-g0001.jpg

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