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有效噬菌体鸡尾酒疗法应对广泛耐药 16 型序列的上升发病率。

Effective phage cocktail to combat the rising incidence of extensively drug-resistant sequence type 16.

机构信息

Department of Medical Microbiology, Division of Infection and Immunity, Cardiff University, Cardiff, UK.

Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina/Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil.

出版信息

Emerg Microbes Infect. 2022 Dec;11(1):1015-1023. doi: 10.1080/22221751.2022.2051752.

Abstract

Bacteriophages are the most abundant organisms on Earth. As there are few effective treatment options against some pathogens, the interest in the bacteriophage control of multi-drug-resistant bacterial pathogens is escalating, especially for . This study aimed to develop a phage-based solution to the rising incidence of extensively drug-resistant clinical sequence type (ST16) infections starting from a set of phages recently characterized against this lineage. A phage-cocktail (Katrice-16) composed of eight lytic phages was characterized for potential use in humans. and broth inhibition and rescue assays were used to demonstrate the efficacy of this approach using a collection of 56 strains of ST16, with distinct genetic backgrounds that were collected from clinical infections from four disparate nations. Additionally, Katrice-16 anti-biofilm activity, synergism with meropenem, and activity in human body fluids were also assessed. Katrice-16 was highly active against our ST16 collection (AUC% median = 86.48%; Q1 = 83.8%; Q2 = 96.85%; Q3 = 98.85%). It additionally demonstrated excellent activity in rescue assays, even with larvae infected by isolates that exhibited moderate inhibition. We measured significant anti-biofilm activity over 12 h ( = .0113) and synergic activity with meropenem. In addition, we also demonstrate that Katrice-16 maintained high activity in human body fluids. Our results indicate that our cocktail will likely be an effective solution for human infections with this increasingly prevalent and often highly resistant bacterial clone.

摘要

噬菌体是地球上最丰富的生物。由于针对某些病原体的有效治疗方法很少,因此人们对噬菌体控制多药耐药细菌病原体的兴趣正在加剧,尤其是对临床分离株。本研究旨在从最近针对该谱系进行表征的一组噬菌体中开发一种基于噬菌体的解决方案,以解决广泛耐药的临床分离株(ST16)感染的发生率不断上升的问题。一种由八种裂解噬菌体组成的噬菌体鸡尾酒(Katrice-16)被表征为具有人类潜在用途。使用 56 株具有不同遗传背景的 ST16 菌株的集合进行了 和肉汤抑制和挽救测定,以证明该方法的有效性,这些菌株是从来自四个不同国家的临床感染中收集的。此外,还评估了 Katrice-16 抗生物膜活性、与美罗培南的协同作用以及在人体体液中的活性。Katrice-16 对我们的 ST16 菌株集合具有高度活性(AUC%中位数 = 86.48%;Q1 = 83.8%;Q2 = 96.85%;Q3 = 98.85%)。它在挽救测定中也表现出出色的 活性,即使感染了显示中度 抑制的分离株的幼虫也是如此。我们在 12 小时内测量到显著的抗生物膜活性( = .0113),并与美罗培南具有协同活性。此外,我们还证明 Katrice-16 在人体体液中保持高活性。我们的结果表明,我们的鸡尾酒很可能成为治疗这种日益流行且通常高度耐药的细菌克隆引起的人类感染的有效解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e2d/9004492/239da6ad535b/TEMI_A_2051752_F0001_OC.jpg

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