Enhancement of tigecycline potency using efflux pump inhibitors
AssigneeMpex Pharmaceuticals, Inc.
InventorsTomasz Glinka, Keith Bostian, Olga Lomovskaya, Mark Surber, Dongxu Sun
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Abstract
Disclosed herein are Efflux Pump Inhibitor (EPI) compounds that can be co-administered with antimicrobial agents for the treatment of infections caused by drug resistant pathogens. The EPI compounds are soft drugs which exhibit a reduced propensity for tissue accumulation. It is demonstrated that the EPIs can be used to increase the potency, decrease bacterial resistance and development of bacterial resistance, and increase killing effectivness of tigecycline. Also disclosed are methods of treatment and pharmaceutical compositions for co-administering tigecylcine with an EPI.
Claims25
A method of increasing susceptibility of a bacterium to tigecycline, comprising contacting the bacterium with an efflux pump inhibitor.
A method of treating a subject having a bacterial infection, comprising co-administering to the subject tigecycline and an efflux pump inhibitor.
A pharmaceutical composition, comprising:
- tigecycline or a prodrug, pharmaceutically acceptable salt, or hydrate thereof;
- and an efflux pump inhibitor.
A method of reducing resistance of a bacterium to tigecycline, comprising contacting the bacterium with an efflux pump inhibitor.
A method of reducing emergence of bacterial resistance to tigecycline, comprising contacting a bacterium with an efflux pump inhibitor, whereby emergence of bacterial resistance to tigecycline in the bacterium is reduced.
A method of increasing bacterial killing effectiveness of tigecycline, comprising contacting a bacterium with an efflux pump inhibitor, whereby the effectiveness of tigecycline to kill the bacterium is increased.
Dependencies are inferred from the claim text.