Abstract

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 infectioncontrol 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.

Biography
Willem Woudstra is a first year PhD student in the biomedical engineering department at the University Medical Center Groningen. His main research goal is developing new strategies for (biomaterial associated) infections in animal models and therewith reduce the number of animals used in future infection studies. After finishing his Bachelor Degree, he started working as a technician and is co-author of several papers in the field of biomedical engineering. His research interests are biofilms, biomaterials associated infections, antimicrobials and animal infection studies.

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