Investigating\nthe Translational Value of Periprosthetic\nJoint Infection Models to Determine the Risk and Severity of Staphylococcal\nBiofilms

With the advent of antibiotic-eluting polymeric materials\nfor targeting\nrecalcitrant infections, using preclinical models to study biofilms\nare crucial for improving the treatment efficacy in periprosthetic\njoint infections. The stratification of risk and severity of infections\nis needed to develop an effective clinical dosing framework with better\ntreatment outcomes. We use in vivo and in vitro implant-associated\ninfection models to demonstrate that methicillin-sensitive and resistant Staphylococcus aureus (MSSA and MRSA) have model-dependent\ndistinct implant and peri-implant tissue colonization patterns. The\nmaturity of biofilms and the location (implant vs tissue) were found\nto influence the antibiotic susceptibility evolution profiles of MSSA\nand MRSA, and the models could capture the differing host–microbe\ninteractions in vivo. Gene expression studies revealed the molecular\nheterogeneity of colonizing bacterial populations. The comparison\nand stratification of the risk and severity of infection across different\npreclinical models provided in this study can guide clinical dosing\nto prevent or treat PJI effectively.