Systemic and local effects of vancomycin-combined thermal exposure on Staphylococcus aureus infected rat femurs: a comparative study of hyperthermia and thermal ablation.

Antibiotic therapy is losing effectiveness against resistant pathogens like Staphylococcus aureus (SA) strains with reduced susceptibility to vancomycin (VMN), particularly in bone infections where drug delivery is difficult. Hyperthermia has emerged as a potential alternative, yet its specific impact on infected bone remains poorly understood. This study investigated the systemic and local effects of combining VMN with local thermal exposure on inflammation and regeneration in rat femurs locally infected with SA strain 209 P insensitive to VMN at an in vitro dose of 10 µg/mL. In vitro, SA growth was assessed after heating at 45 °C and 60 °C for up to 60 min. In vivo experiments involved six groups of rats that received local hyperthermia (45 °C) or thermal ablation (60 °C) for 20 min, with or without systemic VMN administration. At 45 °C, a bacteriostatic effect was achieved after 45-60 min, whereas 60 °C inhibited growth completely within 15 min. In post-hyperthermia at 45 °C, bone tissue showed a regenerative effect comparable to VMN alone and significantly reduced local inflammation. Unexpectedly, combined treatment partially weakened this regenerative benefit. Thermal ablation at 60 °C, while inducing bone regeneration, also elevated markers of systemic inflammation like blood leukocytosis and weight loss, which were partially mitigated by VMN. However, antibiotic showed a negligible effect on local inflammation and reparative processes at this higher temperature. The findings indicate that a single hyperthermia session has more biological promise than thermal ablation as a targeted approach to limit local and systemic inflammation in SA-complicated trauma. Nevertheless, the complex interactions between high temperature and antibiotics warrant further investigation to determine optimal combined therapeutic regimens for osteomyelitis.