Comparison of 3 real-time, quantitative murine models of staphylococcal biofilm infection by using in vivo bioluminescent imaging.

Biofilm formation represents a unique mechanism by which Staphylococcus aureus and other microorganisms avoid antimicrobial clearance and establish chronic infections. Treatment of these infections can be challenging, because the bacteria in the biofilm state are often resistant to therapies that are effective against planktonic bacteria of the same species. Effective animal models for the study of biofilm infections and novel therapeutics are needed. In addition, there is substantial interest in the use of noninvasive, in vivo data collection techniques to decrease the animal numbers required for the execution of infectious disease studies. To address these needs, we evaluated 3 murine models of implant-associated biofilm infection by using in vivo bioluminescent imaging techniques. The goal of these studies was to identify the model that was most amenable to development of sustained infections that could be imaged repeatedly in vivo by using bioluminescent technology. We found that the subcutaneous mesh and tibial intramedullary pin models both maintained consistent levels of bioluminescence for as long as 35 d after infection, with no implant loss experienced in either model. In contrast, a subcutaneous catheter model demonstrated significant incidence of incisional abscessation and implant loss by day 20 after infection. The correlation of bioluminescent measurements and bacterial enumeration was strongest with the subcutaneous mesh model. Among the 3 models we evaluated, the subcutaneous mesh model is the most appropriate animal model for prolonged study of biofilm infections by using bioluminescent imaging.