Adjuvant Photodynamic Therapy to Reduce Bacterial Bioburden in High-Energy Contaminated Open Fractures

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PROJECT SUMMARY This proposal aims to evaluate and optimize Photodynamic Therapy (PDT) as an adjuvant treatment for contaminated high-energy open fractures to reduce bacterial bioburden and, thus, reduce rate of infection. Infection following fracture treatment is one of the most challenging complications facing musculoskeletal trauma patients. Infection can be catastrophic, leading to prolonged morbidity, loss of function, and potential loss of limb. Several factors make high-energy open trauma particularly susceptible to infection: the presence of traumatized tissues, contamination of the fracture, poor soft tissue coverage, poor nutritional state due to polytrauma, prolonged hospitalization with exposure to nosocomial bacteria, and presence of metallic implants. Infection prevention strategies currently employed include systemic antibiotics, thorough surgical debridement of open fracture, local antibiotics, mechanical stability of the extremity with metallic implants as well as soft tissue coverage. However, despite these prevention strategies, infection occurs in 10-60% of open fractures. This is due, at least in part, to inadequate eradication of contaminating bacteria, particularly in the context of hardware at the fracture site. Thus, the overall goal of this proposal is to evaluate the efficacy of PDT at reducing wound bioburden in contaminated high-energy open fracture, thus reducing the risk of fracture related infection in preparation for translation into human patients. The scientific premise of this proposal is underpinned by data from our prior in vitro studies demonstrating enormous efficacy, killing >90% of bacteria in mature established biofilm, which is far superior to currently utilized adjuvant treatment, and our in vivo studies showing eradication of MRSA from contaminated open fracture. To attain our overall objective, three aims will be pursued. In Aim 1 we will optimize the formulation, light dose, and timing of PDT; in Aim 2 we will determine the efficacy of adjuvant topical PDT on two different fixation strategies, which have different consequences in terms of biofilm formation (intramedullary fixation and plate fixation); in Aim 3 we will develop and preliminarily assess the efficacy of repeat PDT administration through a surgically placed extraosseous catheter. Integration of PDT into treatment of high-risk contaminated high-energy open fractures has the potential to revolutionize treatment of these injuries, resulting in a reduction in wound bioburden and, thus, a reduction in risk of infection. This project leverages an extensive infrastructure and experience in fluorescence-guided surgery as well as longstanding collaborations between orthopaedic surgery and biomedical engineers.