The Novel Oxazolidinone TBI-223 Is Effective in Three Preclinical Mouse Models of Methicillin-Resistant Staphylococcus aureus Infection
Oren Gordon, Dustin Dikeman, Roger V. Ortines, Yu Wang, Christine Youn, Mohammed Mumtaz, Nicholas Orlando, Jeffrey Zhang, Aman M. Patel, Ethan Gough, Amit Kaushik, Eric L. Nuermberger, Anna M. Upton, Nader Fotouhi, Lloyd Miller, Nathan K. Archer
Abstract
Staphylococcus aureus is the predominant cause of bloodstream, skin, and bone infections in humans. Resistance to commonly used antibiotics is a growing concern, making it more difficult to treat staphylococcal infections. Use of the oxazolidinone antibiotic linezolid against resistant strains is hindered by high rates of adverse reactions during prolonged therapy. Here, a new oxazolidinone named TBI-223 was tested against S. aureus in three mouse models of infection, i.e., bloodstream infection, skin infection, and bone infection. We found that TBI-223 was as effective as linezolid in these three models. Previous data suggest that TBI-223 has a better safety profile than linezolid. Taken together, these findings indicate that this new agent may provide an additional option against MRSA infections. Future studies in larger animal models and clinical trials are warranted to translate these findings to humans.