A Combination of Carbapenem and Avibactam for Treatment of Bacterial Infections

UNMET NEED
Multidrug-resistant (MDR) pathogens, e.g. Mycobacterium tuberculosis (TB) are a growing threat with significant economic ramifications. In particular, TB is one of the top 10 causes of death worldwide, with an estimated 10.4 million people infected, globally. An estimated 1.8 million deaths are attributable to TB. MDR-TB is TB that does not respond to the 2 most powerful anti-TB drugs, and approximately 500,000 people developed MDR-TB in 2015. Globally, only 52% of MDR-TB patients are successfully treated, demanding new approaches to combating this pathogen. This specific case is part of a larger and growing trend of antibiotic resistance that will require new combative strategies. One such strategy is combining common antibiotics with additional compounds that increase and/or restore the susceptibility of resistant bacteria to current therapeutics. Without a way to restore this susceptibility, the minimum inhibitory concentrations (MICs) for carbapenems to successfully treat MDR pathogens are neither safe nor tolerated in infected individuals.  This invention provides a way to begin developing such a restorative regimen.

TECHNOLOGY OVERVIEW
The inventors have found that a combination of the carbapenem class of antibiotics and avibactam (a beta-lactamase inhibitor) IS POTENT AGAINST Mycobacterium absessus and potentially against other patohogenic bacteria. This discovery presents a unique opportunity to develop a regimen to treat MDR bacterial infections. Notably, a combination of tebipenem, ertapenem, or panipenem with avibactam presented the greatest shift in MIC, indicating that Avibactam restores MICs of carbapenem-class antibiotics against M. abscessus to therapeutically achievable concentrations of the drugs.

STAGE OF DEVELOPMENT
ASSOCIATED PUBLICATIONS
■Kaushik, A, et al. Future Micro. 12.6. 2017

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