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噬菌体疗法与感染性心内膜炎——这现实吗?

Bacteriophage therapy and infective endocarditis - is it realistic?

作者信息

Pedersen Emilie C, Lerche Christian Johann, Schwartz Franziska Angelica, Ciofu Oana, Azeredo Joana, Thomsen Kim, Moser Claus

机构信息

Department of Clinical Microbiology, Copenhagen University Hospital, Copenhagen, Denmark.

Department for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

出版信息

APMIS. 2024 Oct;132(10):675-687. doi: 10.1111/apm.13455. Epub 2024 Jul 15.

Abstract

Infective endocarditis (IE) is a severe infection of the inner heart. Even with current standard treatment, the mean in-hospital mortality is as high as 15-20%, and 1-year mortality is up to 40% for left-sided IE. Importantly, IE mortality rates have not changed substantially over the past 30 years, and the incidence of IE is rising. The treatment is challenging due to the bacterial biofilm mode of growth inside the heart valve vegetations, resulting in antibiotic tolerance. Achieving sufficient antibiotic anti-biofilm concentrations in the biofilms of the heart valve vegetations is problematic, even with high-dose and long-term antibiotic therapy. The increasing prevalence of IE caused by antibiotic-resistant bacteria adds to the challenge. Therefore, adjunctive antibiotic-potentiating drug candidates and strategies are increasingly being investigated. Bacteriophage therapy is a reemerging antibacterial treatment strategy for difficult-to-treat infections, mainly biofilm-associated and caused by multidrug-resistant bacteria. However, significant knowledge gaps regarding the safety and efficacy of phage therapy impede more widespread implementation in clinical practice. Hopefully, future preclinical and clinical testing will reveal whether it is a viable treatment. The objective of the present review is to assess whether bacteriophage therapy is a realistic treatment for IE.

摘要

感染性心内膜炎(IE)是一种严重的心脏内部感染。即使采用当前的标准治疗方法,住院平均死亡率仍高达15% - 20%,左侧IE的1年死亡率高达40%。重要的是,在过去30年里,IE的死亡率并未有实质性变化,且IE的发病率正在上升。由于心脏瓣膜赘生物内细菌的生物膜生长模式,导致抗生素耐受性,治疗具有挑战性。即使采用高剂量和长期抗生素治疗,在心脏瓣膜赘生物的生物膜中达到足够的抗生素抗生物膜浓度也存在问题。由耐抗生素细菌引起的IE患病率不断上升,这增加了挑战。因此,越来越多的人在研究辅助抗生素增效候选药物和策略。噬菌体疗法是一种重新兴起的针对难治性感染的抗菌治疗策略,主要针对生物膜相关且由多重耐药细菌引起的感染。然而,关于噬菌体疗法安全性和有效性的重大知识空白阻碍了其在临床实践中的更广泛应用。希望未来的临床前和临床试验能揭示它是否是一种可行的治疗方法。本综述的目的是评估噬菌体疗法是否是IE的一种切实可行的治疗方法。

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