Synergistic Action of Antimicrobial Peptides and Antibiotics

In recent years, the rapid rise of antimicrobial resistance has intensified the search for alternative agents to treat drug-resistant infections. Antimicrobial peptides (AMPs) are promising therapeutic candidates due to their broad-spectrum activity, diverse mechanisms of action, relatively low risk of resistance development, and potential for use in combination therapies. This review outlines current knowledge on the properties and mechanisms of action of AMPs compared to conventional antibiotics. Furthermore, it discusses synergistic interactions between antimicrobial peptides and antibiotics, focusing on the underlying mechanisms, therapeutic implications, and translational challenges. It also summarizes key in vitro and in vivo studies, demonstrating enhanced antimicrobial efficacy of AMP–antibiotic combinations, including mechanisms such as increased membrane permeability, disruption of intracellular pathways, inhibition of biofilm formation, and efflux pump inhibition. The immunomodulatory and wound-healing properties of AMPs are also highlighted as factors that further strengthen their therapeutic potential in vivo. The review concludes with an overview of the main limitations hindering clinical translation and highlights ongoing research efforts aimed at optimizing AMP-based combination therapies against multidrug-resistant pathogens.