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噬菌体与抗生素联合预防血管移植物感染的体外研究

Combination of Bacteriophages and Antibiotics for Prevention of Vascular Graft Infections-An In Vitro Study.

作者信息

Ruemke Stefan, Rubalskii Evgenii, Salmoukas Christina, Hermes Kristina, Natanov Ruslan, Kaufeld Tim, Gryshkov Oleksandr, Mutsenko Vitalii, Rubalsky Maxim, Burgwitz Karin, Glasmacher Birgit, Haverich Axel, Rustum Saad, Kuehn Christian

机构信息

Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany.

Lower Saxony Centre for Biomedical Engineering, Implant Research and Development, 30625 Hannover, Germany.

出版信息

Pharmaceuticals (Basel). 2023 May 13;16(5):744. doi: 10.3390/ph16050744.

DOI:10.3390/ph16050744
PMID:37242527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10223927/
Abstract

(1) Background: Implant-associated bacterial infections are usually hard to treat conservatively due to the resistance and tolerance of the pathogens to conventional antimicrobial therapy. Bacterial colonization of vascular grafts may lead to life-threatening conditions such as sepsis. The objective of this study is to evaluate whether conventional antibiotics and bacteriophages can reliably prevent the bacterial colonization of vascular grafts. (2) Methods: Gram-positive and Gram-negative bacterial infections were simulated on samples of woven PET gelatin-impregnated grafts using and strains, respectively. The ability to prevent colonization was evaluated for a mixture of broad-spectrum antibiotics, for strictly lytic species-specific bacteriophage strains, and for a combination of both. All the antimicrobial agents were conventionally tested in order to prove the sensitivity of the used bacterial strains. Furthermore, the substances were used in a liquid form or in combination with a fibrin glue. (3) Results: Despite their strictly lytic nature, the application of bacteriophages alone was not enough to protect the graft samples from both bacteria. The singular application of antibiotics, both with and without fibrin glue, showed a protective effect against (0 CFU/cm), but was not sufficient against without fibrin glue (M = 7.18 × 10 CFU/cm). In contrast, the application of a combination of antibiotics and phages showed complete eradication of both bacteria after a single inoculation. The fibrin glue hydrogel provided an increased protection against repetitive exposure to ( = 0.05). (4) Conclusions: The application of antibacterial combinations of antibiotics and bacteriophages is an effective approach to the prevention of bacteria-induced vascular graft infections in clinical settings.

摘要

(1) 背景:由于病原体对传统抗菌治疗具有耐药性和耐受性,植入相关的细菌感染通常难以通过保守治疗治愈。血管移植物的细菌定植可能导致败血症等危及生命的情况。本研究的目的是评估传统抗生素和噬菌体是否能可靠地预防血管移植物的细菌定植。(2) 方法:分别使用 和 菌株在编织PET明胶浸渍移植物样本上模拟革兰氏阳性和革兰氏阴性细菌感染。评估了广谱抗生素混合物、严格裂解的种特异性噬菌体菌株以及两者组合预防定植的能力。对所有抗菌剂进行常规测试以证明所用细菌菌株的敏感性。此外,这些物质以液体形式使用或与纤维蛋白胶联合使用。(3) 结果:尽管噬菌体具有严格的裂解特性,但单独应用噬菌体不足以保护移植物样本免受两种细菌的侵害。单独使用抗生素,无论是否与纤维蛋白胶联合使用,对 均显示出保护作用(0 CFU/cm),但在没有纤维蛋白胶的情况下对 则不足够(M = 7.18 × 10 CFU/cm)。相比之下,抗生素和噬菌体联合应用在单次接种后显示出两种细菌均被完全根除。纤维蛋白胶水凝胶对重复暴露于 提供了增强的保护作用( = 0.05)。(4) 结论:抗生素和噬菌体的抗菌组合应用是临床环境中预防细菌引起的血管移植物感染的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efff/10223927/f6f9b86be2b0/pharmaceuticals-16-00744-g013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efff/10223927/522e91192c00/pharmaceuticals-16-00744-g010.jpg
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