INNOVATIVE DUAL-ANTIBIOTIC DELIVERY SYSTEM PROVIDES INFECTION CONTROL IN A PRECLINICAL DEBRIDEMENT, ANTIBIOTICS, AND IMPLANT RETENTION MODEL OF OSTEOSYNTHESIS-ASSOCIATED OSTEOMYELITIS

Aim This study evaluated the therapeutic efficacy of a carbohydrate-ester-based dual antibiotic formulation (gentamicin/clindamycin; CC-G/C) 1 designed for local, sustained-release treatment of bone and joint infections. A porcine model of acute osteosynthesis-associated osteomyelitis (OAO) undergoing a debridement, antibiotics and implant retention (DAIR) procedure - without administration of systemic antibiotics – was used. Method A locking compression plate with four screws was placed medially on the proximal right tibia of 16 pigs (no fracture) and inoculated with Staphylococcus aureus S54F9 (10 4 CFU). On day three, histology and microbiology confirmed the development of extensive purulent osteomyelitis and soft tissue infection in three pigs, which served as primary infection controls. The remaining 13 pigs underwent a DAIR procedure with purulent drainage, extensive soft tissue debridement, saline irrigation, and implant retention. In nine pigs, 5 mL of CC-G/C was injected around the plate and screws, and into surrounding soft tissue via 23- or 21-gauge needles. Four pigs that underwent DAIR without antibiotics treatment served as controls. Among the nine pigs receiving CC-G/C, three received CC-G/C primarily in the macroscopically infected areas. A more infiltrative approach was applied in the following six pigs, with deeper CC-G/C injections and placement between plate and bone where possible. No systemic antibiotics were administered in any of the pigs. Tibial radiographs were obtained 11 days after the DAIR, and bone, soft tissue, and implants were collected for microbiology and histopathology. Results Purulent osteomyelitis and sequestration were observed in control animals on day 11. The pilot group displayed a reduction of Staphylococcus aureus count compared to untreated controls. The infiltrative treatment approach improved therapeutic outcomes, with three out of six pigs achieving complete eradication of infection in bone, soft tissue and on implants. In the remaining three pigs, only one bone, soft tissue, or implant sample tested positive for Staphylococcus aureus . Histopathology demonstrated tissue biocompatibility of CC-G/C, apparent decreased neutrophil infiltration and reduced pathological bone area compared to controls. Radiographs showed reduced periosteal and endosteal proliferation, and less trabecular and cortical osteolysis. Conclusions Surgical debridement combined with local CC-G/C administration demonstrated strong therapeutic potential in a porcine OAO model without systemic antibiotics, highlighting its potential in DAIR strategies. The thin-needle injectability of CC-G/C enabled precise, tissue-compliant delivery and adequate dose coverage, supporting its use as a targeted and potent antibiotic delivery system. CC-G/C system is a promising adjunct to surgical debridement, offering potential for improved treatment outcomes in DAIR procedures.