Methodology for Monobactam Diversification

University of Notre Dame Background
A. baumannii is a highly virulent bacteria that is present in high-risk settings such as hospitals and front-line clinics. It accounts for about 80% of infections caused by Gram‑negative bacteria and can lead to a variety of illnesses including pneumonia, blood/wound infections, meningitis, urinary tract infection, and central venous catheter-related infection. There is a significant need for new Gram-negative antibiotics that are effective against multi-drug resistant bacteria as A. baumannii can be transmitted over virtually any surface including keyboards, mops, and curtains in addition to already sterilized medical devices. Carbapenems are typically used as a last resort line of attack against multidrug resistant bacteria. However, there is a growing resistance to carbapenems. A novel treatment for A. baumannii and other multi-drug resistant Gram‑negative bacteria would offer the medical profession a potent new tool for treating immunocompromised patients who are most susceptible to these dangerous infections.
Technology Overview
Researchers at the University of Notre Dame have recently developed novel monocyclic beta-lactam antibiotics with excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of A. baumannii. These antibiotics were designed with a bis-catechol conjugate structure that uses essential bacterial iron sequestration processes to facilitate active transport of the compound through bacterial outer membranes. This targeted approach dramatically improves activity against Gram-negative bacteria, including multi-drug resistant bacteria, including those currently listed by the World Health Organization (WHO) as pathogens of critical concern.
Further Details:
Methodology for Monobactam Diversification: Syntheses and Studies of 4-Thiomethyl Substituted β-Lactams with Activity against Gram-Negative Bacteria, Including Carbapenemase Producing Acinetobacter baumannii. J Med Chem. 2017 Nov9;60(21):8933-8944. doi:10.1021/acs.jmedchem.7b01164.
Benefits

Effective against gram-negative multi-drug resistant bacteria, including A. baumannii
Low (more effective) Minimum inhibitory concentration (MIC values) to prevent bacterial growth compared to the current A. baumannii treatment

Applications

Antibacterial agents in hospitals and clinics – $22B Global Market
Treatment for infected individuals – $244M US Market

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