The limitations of mono‐ and combination antibiotic therapies on immature biofilms in a murine model of implant‐associated osteomyelitis

Treatment of implant‐associated orthopedic infections remains challenging, partly because antimicrobial treatment is ineffective after a mature biofilm covers the implant surface. Currently, the relative efficacy of systemic mono‐ and combination standard‐of‐care (SOC) antibiotic therapies over the course of mature biofilm formation is unknown. Thus, we assessed the effects of cefazoline (CEZ), gentamicin (GM), and vancomycin, with or without rifampin (RFP), on Staphylococcus aureus biofilm formation during the establishment of implant‐associated osteomyelitis in a murine tibia model. Quantitative scanning electron microscopy of the implants harvested on Days 0, 3, and 7 revealed that all treatments except CEZ monotherapy significantly reduced biofilm formation when antibiotics started at Day 0 (0.46‐ to 0.25‐fold; p