Description:
Executive Summary
University of Virginia researchers have created novel derivative compounds of FDA-approved drug Nitazoxanide (NTZ) that show reduced toxicity, improved bioavailability and greater efficacy against bacterial infections and biofilms.
Background
Opportunistic hospital-acquired pathogens, including S. epidermidis and S. aureus, are the leading cause of catheter and in-dwelling device-associated infections. Their ability to cause disease depends on adherence to polymer surfaces, where they form biofilms. These infections lead to increased morbidity, mortality, lengths of hospitalizations and total health care costs. Biofilms are also utilized by Enteroaggregative E. coli (EAEC) and are required for persistent colonization and resistance to antibiotics. The emergence of “superbug” methicillin-resistant Staphylococcus aureas (MRSA) underscores the need for new treatments for bacterial infections and their biofilms.
About the Invention
Paul S. Hoffman, Ph.D., and colleagues at the University of Virginia are using a structure-activity relationship (SAR) approach to design novel derivative compounds of the FDA-approved drug, Nitazoxanide (NTZ). These compounds have been found to inhibit growth and biofilm-forming activity. To date, more than 200 compounds have been synthesized, yielding 50 lead compounds that are more effective than NTZ in vitro against a range of organisms, including MRSA, S. epidermidis and E. coli. Additionally, at lower doses, the compounds prevent biofilm formation. Preliminary testing in mice shows very low toxicity and PK/PD, and dosing studies are under way.
The compounds show inhibitory activity in vitro against other disease-causing organisms, including H. pylori, C. difficile and E. histolytica. A description of NTZ-derivative effects on these organisms can be found online.
For more information, see the following inventor publication:
Advantages
These novel compounds offer the following advantages over alternative therapeutics:
- Improved solubility and bioavailability over NTZ
- Low incidence of toxicity and side effects
- Broad spectrum activity against bacterial growth and biofilm formation
- Utility as surface coating for catheters and in-dwelling medical devices
