Flap-Mediated Antibiotic Delivery in Reconstructed Combined Bone and Soft-Tissue Defects: A Translational Porcine Study

Introduction & Aim Effective management of complex tissue defects and bone infections relies on surgical soft-tissue reconstruction combined with adequate local antibiotic delivery. However, antibiotic delivery within the reconstructed combined bone–soft-tissue unit remains poorly characterised. Methods In a controlled large-animal model, combined bilateral tibial bone and soft-tissue defects were created in ten pigs and reconstructed with muscle flaps (n=8), fasciocutaneous flaps (n=8), or direct closure (n=4, controls). Both flaps underwent 60 minutes of arteriovenous clamping to simulate free flap ischaemia. Single intravenous infusions of meropenem (1000 mg) and vancomycin (2000 mg) were administered. Interstitial concentrations were obtained by microdialysis in flap or subcutaneous tissue (controls), at the flap–bone interface, and in underlying cancellous bone. Antibiotic exposure was quantified as the area under the concentration–time curve (AUC0-450). Plasma samples served as a systemic reference. Sampling continued for 450 minutes. Results For both antibiotics, no differences were observed between flap types or direct closures at the flap–bone interface or in cancellous bone. In contrast, differences were observed within flap tissues. Compared with muscle flaps, fasciocutaneous flaps achieved 1.70-fold (95% CI 1.27–2.29) and 1.29-fold (95% CI 1.06–1.58) higher exposure for meropenem and vancomycin, respectively. Direct closure resulted in the highest within soft-tissue exposure. Conclusions Early postoperative antibiotic delivery within the reconstructed surgical site was both tissue and drug-dependent. Although exposure at the flap–bone interface and cancellous bone were comparable across flap types and direct closures, flap composition significantly influenced within-flap exposures. These findings challenge assumptions about flap-mediated antibiotic delivery, and the model provides a reproducible mechanism for investigating systemic and local antibiotic strategies in the management of complex tissue defects and bone infections. Acknowledgements This study was funded by unrestricted grants from the Vissing Foundation, the Laege Sofus Carl Emil Friis and hustru Olga Doris Friis' Grant, the Riisfort Foundation, and the Department of Clinical Medicine, Aarhus University.