INTRODUCTION: Complicated wound infections pose a significant challenge to patient recovery and healthcare systems, particularly due to the emergence of less common but highly resistant multidrug-resistant (MDR) pathogens that undermine the efficacy of conventional antibiotic therapies. This growing threat highlights the urgent need for innovative antimicrobial approaches. METHODOLOGY: In this study, we synthesized eco-friendly silver nanoparticles (AgNPs) using garlic extract to combat complicated wound infections caused by atypical MDR pathogens. RESULTS: Genetic sequencing of 16S rRNA gene, aligned with phenotypic identification methods, confirmed that Escherichia fergusonii (E. fergusonii) as a significant atypical pathogen responsible for complicated wound infections, with a prevalence rate of 24% (12 out of 50 cases). Antimicrobial susceptibility testing revealed that all identified E. fergusonii strains exhibited MDR patterns. Garlic extract, analyzed using GC-MS and UPLC-ESI-MS/MS, identified sulfur-containing bioactive compounds such as allyl methyl trisulfide, dimethyl trisulfide, and allicin, which facilitated the biosynthesis of AgNPs. Stable, spherical AgNPs (15-20 nm) with strong antimicrobial properties were confirmed under optimal conditions (10 mL garlic extract, 40°C, pH 8.0). Their properties were validated using UV-Vis spectroscopy, XRD, and TEM. Antibacterial assays of AgNPs showed mean inhibition zones of 28±0.5 mm and MIC values of 100 µg/mL. TEM analysis revealed that AgNPs compromised bacterial membrane integrity, leading to structural damage, increased permeability, and leakage of intracellular contents. Simultaneously, they induced a concentration-dependent depletion of intracellular glutathione (GSH) in E. fergusonii, suggesting that both membrane disruption and oxidative stress synergistically contribute to bacterial cell lysis and death. A strong synergistic interaction was observed between AgNPs, used at a safe concentration below 50 µM as confirmed by cytotoxicity assays, and antibiotics such as ciprofloxacin, as evidenced by a fractional inhibitory concentration (FIC) index of 0.37. Time-kill assays demonstrated rapid bacterial eradication when AgNPs were combined with antibiotics such as ciprofloxacin. CONCLUSION: These findings underscore the promise of garlic-derived silver nanoparticles (AgNPs) as a fast-acting, eco-friendly option for treating complex wound infections caused by atypical multidrug-resistant (MDR) pathogens.