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抗微生物药物治疗囊性纤维化肺部感染的临床前试验:当前需求和未来重点。

Preclinical testing of antimicrobials for cystic fibrosis lung infections: current needs and future priorities.

机构信息

Microbiomes, Microbes and Informatics Group, Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Park Place, Cardiff, UK.

Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK.

出版信息

Microbiology (Reading). 2023 Jul;169(7). doi: 10.1099/mic.0.001361.

Abstract

A workshop was held by the PIPE-CF strategic research centre to consider preclinical testing of antimicrobials for cystic fibrosis (CF). The workshop brought together groups of people from the CF community to discuss current challenges and identify priorities when developing CF therapeutics. This paper summarizes the key points from the workshop from the different sessions, including talks given by presenters on the day and round table discussions. Currently, it is felt that there is a large disconnect throughout the community, with communication between patients, clinicians and researchers being the main issue. This leads to little consideration being given to factors such as treatment regimes, routes of administration and side effects when developing new therapies, that could alter the day-to-day lifestyles of people living with CF. Translation of numerical data that are obtained in the laboratory to successful outcomes of clinical trials is also a key challenge facing researchers today. Laboratory assays in preclinical testing involve basing results on bacterial clearance and decrease in viable cells, when these are not factors that are considered when determining the success of a treatment in the clinic. However, there are several models currently in development that seek to tackle some of these issues, such as the organ-on-a-chip technology and adaptation of a hollow-fibre model, as well as the development of media that aim to mimic the niche environments of a CF respiratory tract. It is hoped that by summarizing these opinions and discussing current research, the communication gap between groups can begin to close.

摘要

一个由 PIPE-CF 战略研究中心举办的研讨会旨在考虑囊性纤维化 (CF) 的抗菌药物的临床前测试。该研讨会召集了 CF 社区的各个小组,讨论开发 CF 疗法时的当前挑战和确定优先事项。本文总结了研讨会的要点,包括当天演讲者的演讲和圆桌讨论。目前,人们认为整个社区之间存在很大的脱节,患者、临床医生和研究人员之间的沟通是主要问题。这导致在开发新疗法时很少考虑治疗方案、给药途径和副作用等因素,这些因素可能会改变 CF 患者的日常生活。将实验室获得的数值数据转化为临床试验的成功结果也是研究人员目前面临的一个关键挑战。临床前测试中的实验室检测结果基于细菌清除和活细胞减少,而这些因素在确定临床治疗成功时并不被考虑。然而,目前有几种正在开发的模型试图解决其中的一些问题,例如器官芯片技术和中空纤维模型的改编,以及旨在模拟 CF 呼吸道生态位环境的培养基的开发。人们希望通过总结这些意见并讨论当前的研究,能够开始缩小各个小组之间的沟通差距。

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