Silver Nanoparticle-Antibiotic Combinations: A Strategy to Overcome Bacterial Resistance in Escherichia coli, Salmonella Enteritidis and Staphylococcus aureus.

Background/Objectives: Bacterial resistance to antimicrobials is a major global health challenge, limiting the effectiveness of conventional therapies and complicating infection control. The aim of this study was to investigate the antibacterial potential of biologically synthesized silver nanoparticles (Bio-AgNP), alone and in combination with ampicillin (AMP) and enrofloxacin (ENRO), against multidrug-resistant (MDR) bacterial isolates of clinical and veterinary relevance. Methods: The antibacterial activity of Bio-AgNP, AMP, and ENRO, alone or in combination, was assessed against reference strains and MDR isolates of Escherichia coli, Salmonella enterica serovar Typhimurium and Enteritidis, and Staphylococcus aureus. Minimum inhibitory concentration (MIC) values were determined, and bacterial tolerance to prolonged antimicrobial exposure was evaluated. Additionally, assays were conducted to explore potential mechanisms of action, including cell membrane permeability and oxidative stress induction. Results: All bacterial strains developed increased MIC values after prolonged exposure to conventional antibiotics, confirming resistance. Only E. coli developed resistance to Bio-AgNP. Notably, the Bio-AgNP + AMP combination effectively restored susceptibility in E. coli, while only S. Enteritidis developed resistance to this combination upon prolonged exposure. The synergistic effect of Bio-AgNP with conventional antibiotics significantly reduced bacterial growth within two hours, compared with longer times observed in monotherapy. Mechanistic analysis suggested that the combinations increased membrane permeability, facilitating antibiotic entry. Conclusions: Bio-AgNPs combined with AMP or ENRO enhanced antibacterial activity and overcame resistance in MDR isolates, representing a promising therapeutic alternative. The biological synthesis of Bio-AgNPs, capped with organic biomolecules, supports their potential as safe adjuvants to conventional antibiotics in combating MDR bacterial infections.