Preventing bacterial infections from becoming the leading cause of death by the year 2050 requires the development of novel, infection-control strategies, building heavily on biomaterials science, including nanotechnology. Pre-clinical (animal) studies are indispensable for this development. Often, animal infection outcomes bear little relation to human clinical outcome. Here, we review conclusions from pathogen-inoculum dose-finding pilot studies for evaluation of novel infection-control strategies in murine models. Pathogen-inoculum doses are generally preferred that produce the largest differences in quantitative infection outcome parameters between a control and an experimental group, without death or termination of animals due to having reached an inhumane end-point during the study. However, animal death may represent a better end-point for evaluation than large differences in outcome parameters or number of days over which infection persists. The clinical relevance of lower pre-clinical outcomes, such as bioluminescence, colony forming units (CFUs) retrieved or more rapid clearance of infection is unknown, as most animals cure infection without intervention, depending on pathogen-species and pathogen-inoculum dose administered. In human clinical practice, patients suffering from infection present to hospital emergency wards, frequently in life-threatening conditions. Animal infection-models should therefore use prevention of death and recurrence of infection as primary efficacy targets to be addressed by novel strategies. To compensate for increased animal morbidity and mortality, animal experiments should solely be conducted for pre-clinical proof of principle and safety. With the advent of sophisticated in vitro models, we advocate limiting use of animal models when exploring pathogenesis or infection mechanisms.

中文翻译：

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在开发新的感染控制策略的研究中，接受较高的发病率以牺牲更少的动物为交换。

到2050年，要防止细菌感染成为导致死亡的主要原因，就需要发展新型的感染控制策略，并要以包括纳米技术在内的生物材料科学为基础。临床前（动物）研究对于这一发展是必不可少的。通常，动物感染的结果与人类临床结果关系不大。在这里，我们审查病原体剂量寻找试验研究的结论，以评估鼠模型中新型感染控制策略。通常优选在对照组和实验组之间在定量感染结果参数上产生最大差异的病原菌剂量，而不会由于研究中达到非人道的终点而导致动物死亡或终止。然而，与结果参数或感染持续天数的巨大差异相比，动物死亡可能是一个更好的评估终点。较低的临床前结果（如生物发光，恢复的菌落形成单位（CFU）或更快地清除感染）的临床相关性尚不清楚，因为大多数动物无需干预即可治愈感染，具体取决于病原体种类和病原体接种剂量。在人类临床实践中，遭受感染的患者经常在威胁生命的情况下到医院急诊室就诊。因此，动物感染模型应将死亡和感染复发的预防作为主要功效目标，并通过新策略加以解决。为了补偿增加的动物发病率和死亡率，仅可进行动物实验以进行临床前的原理和安全性证明。随着复杂的体外模型的出现，我们提倡在探索发病机理或感染机制时限制使用动物模型。