Development and Validation of a Multi-dose Neutropenic Rat Thigh Infection Model Using Real-time Monitoring of Staphylococcus aureus Growth In Vivo

Abstract

Background: Several animal models have been described using luminescent bacteria for non-invasive, real-time monitoring of infection in mice. In this study, a multi-dose rat thigh infection model with luminescent Staphylococcus aureus was developed for the evaluation of antibiotic efficacy. Materials and Methods: Bioluminescent imaging and bacterial loads of S. aureus infected rat thighs with or without vancomycin treatment at different time-points post-infection were compared. Results: Correlation between luminescence and bacterial load was observed based on the dose- and time-dependent activity of vancomycin in the model. Conclusion: While luminescence detection offered the advantage of monitoring an infection in live animals, limitations to this method included reduced sensitivity and a narrow dynamic range, as compared to a traditional tissue culturing method. Real-time luminescence monitoring of infection may be most appropriate for experiments where rapid in vivo assessment of compound efficacy is desired and absolute quantitation of colony forming units in infected tissue is not required.