Antibiotic Adjuvants: Make Antibiotics Great Again!

Multiple approaches have been developed to combat bacterial resistance. However, the combination of antibiotic resistance mechanisms by bacteria and the limited number of effective antibiotics available decreases the effective interventions for the treatment of current bacterial infections. This review covers the many ways that bacteria resist antibiotics including antibiotic target modification, the use of efflux pumps, and antibiotic inactivation. As a pertinent example, the use of beta lactamase inhibitors in combination with beta-lactam containing antibiotics is discussed in detail. The solution to emerging antibiotic resistance may involve combination therapies of existing antibiotics and potentiating adjuvants, which re-empower the antibiotic agent to become efficacious against the resistant strain of interest. We report herein that a reasoned adjuvant design permits one to perform polypharmacy on bacteria by not only providing greater internal access to the codosed antibiotics but also by de-energizing the efflux pumps used by the bacteria to escape antibiotic action.