Chemical Basis of Combination Therapy to Combat Antibiotic Resistance

The antimicrobial resistance crisis is a global health issue requiring discovery and development of novel therapeutics. However, conventional screening of natural products or synthetic chemical libraries is uncertain. Combination therapy using approved antibiotics with inhibitors targeting innate resistance mechanisms provides an alternative strategy to develop potent therapeutics. This review discusses the chemical structures of effective beta- lactamase inhibitors, outer membrane permeabilizers, and efflux pump inhibitors that act as adjuvant molecules of classical antibiotics. Rational design of the chemical structures of adjuvants will provide methods to impart or restore efficacy to classical antibiotics for inherently antibiotic-resistant bacteria. As many bacteria have multiple resistance pathways, adjuvant molecules simultaneously targeting multiple pathways are promising approaches to combat multidrug-resistant bacterial infections.

Automated summary

The antimicrobial resistance crisis is a global health issue that requires the discovery and development of new therapeutic methods. Conventional screening methods for natural products or synthetic chemical libraries are uncertain. Combination therapy using approved antibiotics and inhibitors that target innate resistance mechanisms is an alternative strategy for developing potent therapeutics. This review discusses the chemical structures of effective beta-lactamase inhibitors, outer membrane permeabilizers, and efflux pump inhibitors that act as adjunct molecules to classical antibiotics. Rational design of adjunct chemical structures provides methods to enhance or restore the efficacy of classical antibiotics against inherently antibiotic-resistant bacteria. Simultaneously targeting multiple pathways with adjunct molecules shows promising approaches to combat multidrug-resistant bacterial infections.