Efficacy of lysostaphin-coated titanium plates on implant- associated MRSA osteitis in minipigs

Abstract

Abstract Purpose. The growing incidence of implant-associated infections (IAIs) caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance to antibiotics requires new therapeutic strategies. Lysostaphin has been shown to eliminate this biofilm. Own studies confirm the effectiveness in a murine model. The current study characterizes the effects of lysostaphin-coated plates in an IAI minipig model. Methods. The femur of 30 minipigs was stabilized with a 5-hole plate, a bone defect was created, and in 20 cases methicillin-resistantStaphylococcus aureus was applied. 10 animals served as control group. After 14 days, local debridement, lavage, and plate exchange (7-hole plate) were performed. 10 of the infected minipigs received an uncoated plate and 10 a lysostaphin-coated plate. On day 84, the minipigs were again lavaged, followed by euthanasia. Bacterial load was quantified by colony-forming units (CFU). Immunological response was determined by neutrophils, as well as interleukins. Fracture healing was assessed radiologically. Results. CFU showed significant difference between infected minipigs with uncoated plate and minipigs with lysostaphin-coated plate (p=0.0411). The infection-related, excessive callus formation and calcification was significantly greater in the infected animals with uncoated plate than in animals with lysostaphin-coated plate (p=0.0164 / p=0.0033). The analysis of polymorphonuclear neutrophils and interleukins did not reveal any pioneering findings. Conclusion. This study confirms the minipig model for examining IAI. Furthermore, coating of plates using lysostaphin could be a promising tool in the therapeutic strategies of IAI. Future studies should focus on coating technology of implants and on translation into a clinical model.