Investigating the Translational Value of Periprosthetic Joint Infection Models to Determine the Risk and Severity of Staphylococcal Biofilms

With the advent of antibiotic-eluting polymeric materials for targeting recalcitrant infections, using preclinical models to study biofilms are crucial for improving the treatment efficacy in periprosthetic joint infections. The stratification of risk and severity of infections is needed to develop an effective clinical dosing framework with better treatment outcomes. We use in vivo and in vitro implant-associated infection models to demonstrate that methicillin-sensitive and resistant <i>Staphylococcus aureus</i> (MSSA and MRSA) have model-dependent distinct implant and peri-implant tissue colonization patterns. The maturity of biofilms and the location (implant vs tissue) were found to influence the antibiotic susceptibility evolution profiles of MSSA and MRSA, and the models could capture the differing host-microbe interactions in vivo. Gene expression studies revealed the molecular heterogeneity of colonizing bacterial populations. The comparison and stratification of the risk and severity of infection across different preclinical models provided in this study can guide clinical dosing to prevent or treat PJI effectively.