Also referred to as neutropenic thigh infection model.
A highly standardized in vivo system for initial evaluation of antimicrobials in a mammalian system.
The neutropenic thigh mouse model has been extensively used in in vivo studies to test the antimicrobial drug activity of promising molecules under standardized conditions. All currently used antimicrobial classes have been evaluated in this model.
The model is based on direct injection of bacteria into the thighs of animals; this is to mimic human soft tissue infection. Because animal species differ in their intrinsic susceptibility to infection, for thigh infections in mice to resemble those seen in humans, mice immune responses need to be dampened. To this end, mice are treated a few days before infection with an agent (e.g. cyclophosphamide) causing a temporary depletion of neutrophils and thus rendering the mice neutropenic and more susceptible to infections.
The neutropenic mouse model is usually the first in vivo model system used in antimicrobial preclinical drug development. It is typically used to explore the effects of new antibiotics on bacterial growth and animal survival, as well as their pharmacokinetics and pharmacodynamics through testing of different doses and dose frequencies. Its main advantages are its simplicity, high degree of standardization, and reproducibility.
Despite significant differences between mice and humans, results from neutropenic mouse model studies are good predictors of effects in patients.
How preclinical infection models help define antibiotic doses in the clinic (International Journal of Antimicrobial Agents, 2020)
Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases (BMC Infectious Diseases, 2006)
Generating Robust and Informative Nonclinical In Vitro and In Vivo Bacterial Infection Model Efficacy Data To Support Translation to Humans (Antimicrobial Agents and Chemotherapy, 2019)
REVIVE Webinar: ‘PK/PD murine infection models: Focus on study elements, variability, and interpretation of results’ by Alexander J. Lepak (GARDP, 2020)