Alternative Approaches to Combat Antimicrobial Resistance and Improve Antimicrobial Efficacy

Abstract Antimicrobial resistance (AMR) is a rising global health problem that undermines the effectiveness of conventional antibiotics and threatens to compromise infectious disease control. With the conventional antibiotic discovery pipeline running low, there is an urgent need to create novel and adjunctive solutions that circumvent existing resistance mechanisms and restore antimicrobial efficacy. This review addresses new strategies against AMR by controlling bacterial survival, virulence, and resistance mechanisms through new and multipotential mechanisms. New therapies such as antimicrobial peptides, bacteriophage therapy, CRISPR-Cas antimicrobials, β-lactamase inhibitors, antivirulence compounds, macrolones, photodynamic therapy, and bioactive phytochemicals are reviewed according to their capacity to bypass or prevent resistance development. The synergistic use of antibiotic adjuvants and potentiators – molecules that enhance drug entry or inhibit resistance enzymes – offers a robust strategy to revitalize existing antibiotics. The integration of advanced diagnostic technologies, including speedy molecular diagnostics and phenotypic testing, enables directed therapy and avoids unnecessary use of antibiotics, consequently minimizing selection pressure. Collectively, these new strategies form a multipronged strategy to improve antimicrobial performance and are central to global action against the AMR threat.