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Abstract：
Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, is increasingly recognized as an important pathogen of the human lung, disproportionally affecting people with cystic fibrosis (CF) and other susceptible individuals with non-CF bronchiectasis and compromised immune functions. M. abscessus infections are extremely difficult to treat due to intrinsic resistance to many antibiotics, including most anti-tuberculous drugs. Current standard-of-care chemotherapy is long, includes multiple oral and parenteral repurposed drugs, and is associated with significant toxicity. The development of more effective oral antibiotics to treat M. abscessus infections has thus emerged as a high priority. While murine models have proven instrumental in predicting the efficacy of therapeutic treatments for M. tuberculosis infections, the preclinical evaluation of drugs against M. abscessus infections has proven more challenging due to the difficulty of establishing a progressive, sustained, pulmonary infection with this pathogen in mice. To address this issue, a series of three workshops were hosted in 2023 by the Cystic Fibrosis Foundation (CFF) and the National Institute of Allergy and Infectious Diseases (NIAID) to review the current murine models of M. abscessus infections, discuss current challenges and identify priorities toward establishing validated and globally harmonized preclinical models. This paper summarizes the key points from these workshops. The hope is that the recommendations that emerged from this exercise will facilitate the implementation of informative murine models of therapeutic efficacy testing across laboratories, improve reproducibility from lab-to-lab and accelerate preclinical-to-clinical translation.
摘要：
脓肿分枝杆菌,一种快速生长的非结核分枝杆菌，越来越被认为是人类肺部的重要病原体，不成比例地影响患有囊性纤维化（CF）的人和其他患有非CF支气管扩张和免疫功能受损的易感个体。由于对许多抗生素的内在耐药性，脓肿分枝杆菌感染极难治疗。包括大多数抗结核药物.目前的标准化疗时间很长，包括多种口服和肠胃外再利用药物，并与显著的毒性有关。因此，开发更有效的口服抗生素来治疗脓肿分枝杆菌感染已成为高度优先事项。虽然鼠模型已被证明有助于预测结核分枝杆菌感染的治疗性治疗的疗效，针对脓肿分枝杆菌感染的药物的临床前评估已被证明更具挑战性，持续,这种病原体在小鼠中的肺部感染。为了解决这个问题，由囊性纤维化基金会（CFF）和国家过敏和传染病研究所（NIAID）于2023年主办了一系列三个研讨会，以审查当前的小鼠脓肿分枝杆菌感染模型，讨论当前的挑战，并确定建立经过验证和全球统一的临床前模型的优先事项。本文总结了这些研讨会的要点。希望从这项工作中得出的建议将有助于在实验室中实施信息丰富的小鼠治疗功效测试模型，提高从实验室到实验室的可重复性，加速临床前到临床的转化。
