PRECLINICAL IN VIVO MODELS OF FRACTURE-RELATED INFECTION: A SYSTEMATIC REVIEW AND CRITICAL APPRAISAL

A fracture-related infection (FRI) is an important complication that can lead to an increase in morbidity, mortality and economic costs. Preclinical in vivo models are critical in the evaluation of novel prevention and treatment strategies, yet it is important that these studies recapitulate the features of an FRI that make it such a clinical challenge. The aim of this systematic review was to survey the available preclinical models of FRIs and assess which of the key FRI-specific parameters are incorporated in these models. A comprehensive search was performed on July 1st 2017 in PubMed, Embase and Web of Science. Overall, 75 preclinical studies were identified, 97.3 % (n = 73) of which use Staphylococcus aureus as the causative microorganism. The most common mode for creation of bone instability is an osteotomy (n = 30; 40 %), followed by the creation of a defect (n = 26; 34.7 %). An actual fracture is created in only 19 studies (25.3 %). 12 (16 %) of the models include a time gap between bacterial inoculation and fixation to mimic the time-to-treatment in clinical open fracture scenarios. This systematic review reveals that animal models used in translational research on prevention and treatment of FRIs rarely incorporate all key clinical features in one model and that there is an over-representation of S. aureus in comparison to actual clinical epidemiology. To improve the relevance of these studies, existing preclinical models should be adapted or new models developed that better recapitulate the clinical condition of an FRI.