Abstract
The global rise of multidrug-resistant (MDR) bacterial infections presents a significant challenge to modern healthcare, rendering many conventional antibiotics ineffective. This study investigates the synergistic antibacterial potential of silver nanoparticles (AgNPs) combined with amoxicillin against clinically important MDR bacterial pathogens, including Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. AgNPs were synthesized via chemical reduction and characterized by UV-Visible spectrophotometry and X-ray diffraction (XRD), confirming the formation of stable, spherical, crystalline nanoparticles with a surface plasmon resonance peak at 418 nm and diffraction peaks corresponding to face-centered cubic (FCC) silver. Antimicrobial efficacy was assessed through minimum inhibitory concentration (MIC) determination, checkerboard synergy assays, and time-kill kinetics. The results revealed a substantial enhancement in the antibacterial activity of amoxicillin when combined with AgNPs. MIC values of amoxicillin were reduced by 4- to 8-fold in all strains, with final concentrations ranging from 8 to 32 µg/mL compared to initial values of 64 to >128 µg/mL. FICI values ranged from 0.28 to 0.49, indicating strong synergistic effects. Notably, S. aureus exhibited complete bacterial eradication within 12 hours, while other strains showed ≥3 log₁₀ CFU/mL reductions within 6–12 hours in time-kill assays. These findings suggest that AgNPs significantly enhance the efficacy of amoxicillin through multiple mechanisms, including disruption of bacterial membranes and increased intracellular antibiotic uptake. The synergistic interaction observed offers a promising strategy for combating antibiotic resistance in MDR pathogens. Future in vivo studies and clinical evaluations are essential to validate the therapeutic potential and safety of AgNP-antibiotic combination therapies.