Combination Antibiotic Therapy to Exploit Multiple Heteroresistance

Application

Treatment with combinations of FDA-approved antibodies targeting small drug-resistant cell populations for infectious disease.

Key Benefits

Specific combinations of existing drugs that target small subpopulations of bacterial cells resistant to many standard of care treatment regimens.
Potential to overcome the drug resistance crisis leading to decreased morbidity and mortality.
Applicable to a number of gram-negative and gram-positive antibiotic-resistant infections.

Market Summary

Antibiotic resistance is one of the most significant health-related challenges as it limits the efficacy of antibiotics previously responsible for saving millions of lives. The resistance crisis is primarily attributed to the overuse and misuse of these medications and the pharmaceutical industry's lack of new drug development. Typically, resistance involves the resistance of all bacterial cells in the population being resistant to the antibiotic; however, the paradigm has changed via heteroresistance, where the presence of small subpopulations of bacterial cells leads to high levels of antibiotic resistance. Hence, developing treatments that can target the small resistant subpopulations of cells may reduce the high morbidity of these infections.

Technical Summary

Researchers at Emory have identified combinations of drugs for the treatment of drug-resistant bacterial infections. Through several experiments, the inventors discovered small populations of cells were resistant to FDA-approved therapies, colistin or Fosfomycin, when used as a monotherapy. However, combining the two drugs targets multiple heteroresistance cell types, leading to improved bacterial cell killing compared to either agent alone. These data suggest that combining the drugs in the clinic may provide substantial benefits to patients.