Intramedullary antibiotic therapy for the treatment of osteomyelitis

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 DESCRIPTION (provided by applicant): Osteomyelitis is an inflammatory process caused by bacterial infection of the bone. The infection is generally limited to a local area of bone and surrounding soft tissue resulting from bacterial contamination following musculoskeletal injury. Treatment of bone infections can be difficult due to poor penetration of antibiotics into the infected tissue owing to the physiologica and anatomical characteristics of bone, the increased prevalence of infections caused by antibiotic resistant pathogens, and the protective properties of biofilms formed by the infecting bacteria. Extremity injuries are the most common injuries associated with infection complications in the battlefield. Approximately 15% of these patients develop osteomyelitis, and of those, ~17% suffer from infection relapse or recurrence. An increasing number of active duty personnel are receiving their care at VA facilities and a significant proportion of these patients suffer from musculoskeletal infections. With the increasing prevalence of pathogens resistant to antibiotics, treatment of infections has become more challenging. Current standard treatments for infected bones require adequate debridement of the involved or exposed bone with systemic administration of antibiotics, which can last for weeks and have potential toxicities. Despite current infection intervention strategies implemented to treat combat-related injuries in soldiers, one- third of such injuries have been complicated by infection. The direct medical costs relating to the treatment of osteomyelitis has previously been found to be approximately $35,000 per patient. Our lab has challenged the current paradigm that bone infections require long durations of systemic antibiotics. We have developed a model for local intramedullary delivery of antibiotics into long bones. Our delivery system allows for the repeated dosing of antibiotic to an infected rat tibia model. We have shown that local delivery of antibiotic can result in high therapeutic levels of drug locally while maintaining low systemic levels. Using this model, we will test whether local antibiotic delivery results in improved resolution of infection in a rat tibial osteomyelitis model while maintaining bone integrity and reducing systemic drug concentrations and resultant toxicities compared to traditional systemic delivery. Additionally, we will evaluate this local delivery method in the setting of a contaminated fracture model to determine whether local antibiotic delivery can prevent infection and allow for fracture healing compared to controls Outcomes will be evaluated by radiographic resolution of infection, bioluminescent resolution of infection, bone culture and histology. We expect that local antibiotic delivery will result in fastr and more effective resolution of osteomyelitis and will prevent the development of infection in the contaminated fracture model, without the untoward effects of lengthy systemic antibiotic therapy. The results of this study will allow us to translate this technique to clinical practice ad offer patients that suffer from osteomyelitis or contaminated fractures as the result of combat or non-combat trauma a chance at improved recovery and easier re-integration into society and normal activities.