Synergistic Antibacterial Activity of Polyelectrolyte-capped Silver Nanoparticles Combined with Aminoglycoside Antibiotics Against Healthcare-associated Pathogens

Background: The rapid emergence of healthcare-associated infections is rising, driven by diverse etiologic agents whose evolving antimicrobial resistance poses a growing threat to global healthcare. Therefore, combination strategies integrating antibiotics with silver nanoparticles (AgNPs) have attracted increasing attention as a potential means of restoring antibacterial efficacy. Aim: This study aimed to synthesize and validate polyelectrolyte-coated AgNPs and evaluate their synergistic antibacterial effects with aminoglycosides against healthcare-associated pathogens. Methods: Alginate- and chondroitin sulfate-coated AgNPs were synthesized using glucose as a green reducing agent. NP formation was confirmed by physicochemical characterization, followed by cell-based cytotoxicity assessment. The antibacterial activity of AgNPs, alone or in combination with amikacin or tobramycin, was evaluated against six healthcare-associated infection (HAI)-related pathogenic bacterial species. Results: Physicochemical analyses confirmed the formation of spherical metallic AgNPs. Both AgNP formulations showed minimal cytotoxicity at silver concentrations ≤40 ppm but exhibited limited antibacterial activity when used alone. In contrast, combinations of aminoglycosides with AgNPs exhibited species-dependent synergistic effects, with tobramycin–AgNP combinations consistently demonstrating synergistic effects against all six HAI-related pathogenic bacterial species. Conclusion: AgNP–aminoglycoside combinations represent a promising therapeutic strategy for HAI bacterial infections and may help reduce the reliance on the development of novel antibiotics.