Drug resistance is now a global problem causing bacterial infections which cannot be treated with existing antibiotics and is worsened by the limited prospects for development of new effective antimicrobials. In burn centers around the world, a special problem is posed by the development and appearance of vancomycin resistant enterococci (VRE) and the increased incidence of methicillin resistant Staphylococcus aureus (MRSA) for which vancomycin is the treatment of choice. The stage is now set, reports Holder, for crisis limiting treatment options for burn victims. Despite the use of a variety of therapeutic countermeasures, including intravenous immunoglobulins (IVIG) to prevent burn wound infection by S. aureus and P. aeruginosa, more than 2,500 burn victims die in the U.S. every year from sepsis. To overcome the threat posed by antibiotic resistant strains of bacteria, this SBIR proposes to use Passive Local Immunotherapy (PLI), i.e. the direct local application of IgG, (natural antibodies) to burn wounds as a broad spectrum prophylactic and therapeutic countermeasure independent of antibiotic resistant mechanisms. This novel use of pooled human immunoglobulins (IgG), containing natural polyclonal antibodies to contemporary antibiotic resistant pathogenic bacteria, applied locally to burn tissues to prevent and treat antibiotic resistant infection, is cost-effective and overcomes the inherent limitations of IVIG therapy. Preliminary studies with the direct local use of IgG have demonstrated efficacy in preventing Staphylococcal and Pseudomonas infections in closed abscess and intraperitoneal wound infection models. IgG is known to increase opsonization, agglutination and bacterial killing and may also directly inactivate the inoculum. Phase I of this proposal will demonstrate proof of concept for PLI in preventing MRSA and other clinically relevant bacterial burn wound infections and determine a potential treatment regime and carrier for the therapeutic. Phase II will develop ideal IgG antibody compositions and controlled release carriers for clinical use and subsequent commercialization.
This proposal responds to the need for an effective method to control infection, particularly antibiotic resistant infection, in burn wounds. The burn market is estimated at over 2 million patients a year costing an estimated $6 billion to treat. Burn wound sepsis kills more than 2,500 Americans annually.
| Felts, A G; Giridhar, G; Grainger, D W et al. (1999) Efficacy of locally delivered polyclonal immunoglobulin against Pseudomonas aeruginosa infection in a murine burn wound model. Burns 25:415-23 |
