The silver oxide nanoparticles (AgO2-NPs) were synthesised using silver foil as a new precursor in wet chemical method. X-ray diffraction analysis shows crystallographic structures of AgO2-NPs with crystallite size of 35.54 nm well-matched with standard cubic structure. Scanning electron microscopy analysis clearly shows the random distribution of spherical-shaped nanoparticles. Energy dispersive X-ray analysis confirmed the purity of the samples as it shows no impurity element. Fourier transforms infra-red analysis confirmed the formation of AgO2-NPs with the presence of Ag-O-Ag stretching bond. All the techniques also confirmed the loading of ceftriaxone drug on the surface of AgO2-NPs. This study also described the effect of AgO2-NPs having synergistic activity with β lactam antibiotic i.e. ceftriaxone against ESBL generating Escherichia coli (E. coli). Among isolated strains of E. coli, 60.0% were found to be ESBL producer. The synergistic activities of AgO2-NPs with ceftriaxone suggest that these combinations are effective against MDR-ESBL E. coli strains as evident by increase in zone sizes. The present study observed rise in MDR-ESBL E. coli with polymorphism of blaCTXM and blaSHV causing UTI infections in Pakistani population. The antibiotic and AgO2-NPs synergistic effect can be used as an efficient approach to combat uro-pathogenic infections.