Multi-drug resistant Staphylococcus aureus is a significant cause of both nosocomial and community-acquired infections. In the past, powerful antibiotic drugs have provided effective treatments for staphylococcal infections. However, each antibiotic introduced has been met by the emergence of drug resistant staphylococcal strains. Importantly, with the global emergence of S. aureus strains with reduced susceptibility to vancomycin, it is anticipated that fully resistant strains may be detected in the near future. This disconcerting scenario, coupled with the lack of new therapeutics against S. aureus in clinical trials mandate the need to support the development of novel strategies to prevent S. aureus related infections. Inhibitex, Inc. is developing a novel Immune Globulin Intravenous (Human) (abbreviated as SA-IGIV) targeted against multi-drug resistant S. aureus. SA-IGIV is a purified immunoglobulin G product derived from pooled adult human plasma selected for high titers of antibody to S. aureus adhesins, specifically, Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMTM) proteins. The MSCRAMMTM specific IgG in SA-IGIV binds to MSCRAMM proteins on the surface of S. aureus and inhibits the adhesion of the organism to extracellular matrix molecules, prevents colonization, and enhances the phagocytosis by the immune system. The focus of this proposal is the clinical development of SA-IGIV that would be used to treat patients with persistent S. aureus bacteremia. Specifically, the Phase II Challenge Grant will be used to (I) evaluate in a pilot study the safety and tolerability of SA-IGIV administered as a single dose in a Phase 1/Phase 2 clinical trial under the clinical condition of persistent S. aureus bacteremia due to left-sided endocarditis, (2) evaluate the efficacy and pharmacokinetics of SA-IGIV at a single dose under the clinical condition of persistent S. aureus bacteremia due to left-sided endocarditis, and (3) pending positive data from the first clinical trial, determine the efficacy of SA-IGIV in additional high morbidity and mortality S. aureus mediated infections.
