Small molecule efflux pump inhibitors
Small molecule efflux pump inhibitors are provided, as well as methods for their use in treating infections. Also provided herein are methods of using the small molecule efflux pump inhibitors to restore the antibiotic susceptibility of microbes.
1. A method for treating a microbial infection in a subject, comprising administering to the subject an effective amount of an efflux pump inhibitor of the following formula:
and
an antimicrobial agent.
2. The method of claim 1 , further comprising selecting a subject infected with a microbe that is resistant to the antimicrobial agent.
3. The method of claim 2 , wherein the resistance is mediated by an efflux pump.
4. The method of claim 1 , wherein the microbial infection is a bacterial infection.
5. The method of claim 4 , wherein the bacterial infection is a gram-negative bacterial infection.
6. The method of claim 4 , wherein the bacterial infection is a gram-positive bacterial infection.
7. The method of claim 1 , wherein the antimicrobial agent is selected from the group consisting of minocycline, ciprofloxacin, levofloxacin, nalidixic acid, amikacin, gentamycin, kanamycin, meropenem, ceftriaxone, erythromycin, colistin polymxin B, sulfamethoxazole, tigecycline, tobramycin, and trimethoprim.
8. The method of claim 1 , wherein the efflux pump inhibitor and the antimicrobial agent are administered sequentially or simultaneously.