Diabetes mellitus is a major public health problem in Qatar with a prevalence rate reaching 17% in national citizens. Increased susceptibility to microbial infections is common among chronic diabetic patients and is associated with serious complications and increased morbidity and mortality. The mortality rate of invasive bacterial infections has reduced significantly since the introduction of antibiotic therapy. However, the resistance to antibiotics is becoming a serious medical problem contributing to the high medical cost. The team’s overall aim is to deploy a potential inorganic route (metalo-antibiotic) to treat localized infections that require long-term antibiotic treatment combined with medical and surgical intervention. They have selected osteomyelitis (bone infection) as a model to evaluate the inorganic route to treat infection. Osteomyelitis is being seen with increasing frequency in patients with chronic diseases such as diabetes and peripheral vascular disease and in patients with poor dental hygiene. Osteomyelitis is a progressive infection that could result in limb amputation or patient death. The team has synthesized a unique composition of particles that are able to extend their residual efficacy on bacteria for an extended time compared to conventional antibiotics. In their in vitro preliminary experiments, it was demonstrated that metalo-antibiotics are effective against intracellular bacterial infections without damaging the host cells. The in vivo experiments demonstrated a tolerance of the particles for doses up to 20 times higher than the anticipated treatment dose. The data showed that administering metalo-antibiotic intramuscularly induced a significant reduction in bacterial CFUs in the infected tibia of BALB/c mice. The team has designed an approach to evaluate three specific aims that consider the suitability of treating osteomyelitis with metalo-antibiotics composed of Ag-Cu-B. The specific aims are (1) engineer site-specific metalo-antibiotic delivery vehicles. The designed capsule will be engineered with ligands that specifically target the infection sites. The efficacy of the engineered theranostic vehicle will be first evaluated in vitro (2) perform toxicology assessment of the engineered theranostic compounds in vivo to predict safety in humans and (2) perform efficacy assessment of engineered theranostics against osteomyelitis in a mouse model to predict effectiveness for treating localized infection in humans. Overall, the project will have two main impacts: a) creation of novel inorganic nano-based composites to fight against bacterial infections particularly those requiring long-term antibiotic or surgical treatment and/or are polymicrobial b) reduction of critical technical risk through the generation of pre-clinical data of the employment of inorganic antibacterial complexes.
$649,434.00 for three years