Disease models

Mice with femoral implants could be used to model MRSA infection of orthopedic implants. The model involves implanting a titanium Kirschner wire in the intramedullary cavity of the femur of mice, then injecting the mice IV with a MRSA strain expressing luciferase to monitor the infection via whole-animal bioluminescent imaging. The model recapitulated the abscess formation in the marrow cavity, high neutrophil levels in the marrow cavity and knee joint, and biofilm formation on the implant observed in patients with MRSA infections of orthopedic implants. In the model, pretreatment before MRSA infection with a combination of a mAb against bacterial ClfA and a mAb targeting a S. aureus toxin (MEDI4893) decreased the incidence of implant infection, bacterial burden at the implant site and biofilm formation on the implants compared with a control mAb. Next steps by the MedImmune LLC unit of AstraZeneca plc include developing undisclosed therapies screened in the model. ...