Efficacy Enhancement of Cefepime with Lemon Leaf-Reduced Silver Nanoparticles against Drug-Resistant Bacteria

Antibiotic-resistant bacterial strains and their massive proliferation of infectious diseases present a critical challenge for treatment with conventional antibiotics i.e. cefepime. To address this, the present investigation explores an eco-friendly approach to enhance cefepime's antibacterial efficacy with silver nanoparticles biologically synthesized using lemon leaf extract as a reducing agent. The concentration, functional groups, structural morphology, elemental analysis and crystalline phase purity, all were confirmed through various characterization techniques i.e. UV-Vis, FT-IR, SEM-EDX, and XRD, respectively. Further, antibacterial analysis was carried out through agar well diffusion, MIC and anti-biofilm assay against Gram-positive strain S. aureus (ATCC 25923) and Gram-negative strain E. coli (ATCC 15597), while biosafety potential was investigated via antioxidant, hemolysis and anti-inflammatory assays. The cefepime-conjugated silver nanoparticles (CEF-Ag NPs) exhibited significantly enhanced antibacterial efficacy compared to cefepime itself, showing inhibition zones of 25 ± 0.5 mm (S. aureus) and 22 ± 0.6 mm (E. coli) at MIC value of 100 ± 0.01 µg/mL. In addition, biofilm inhibition assay demonstrated a substantial reduction in biofilm formation, with optical densities decreasing from 0.55 ± 0.03 at 100 µg/mL to 0.20 ± 0.01 at 1000 µg/mL. Biological safety evaluations showed hemolysis rate of 3.5 ± 0.2% at 200 µg/mL. Regarding DPPH radical scavenging, it was observed with 81 ± 0.03% at 125 µg/mL, and 85 ± 0.04% reduction in inflammation at 125 µg/mL. These findings suggested that CEF-Ag NPs have not only enhanced antimicrobial efficacy but it is also biocompatible, making a promising candidate for combating multidrug-resistant bacterial infections.