Background: The emergence of multidrug-resistant (MDR) uropathogens has become a public health threat and current knowledge of the genotypic basis of bacterial resistance is essential for selecting appropriate treatment options. Objectives: To determine the prevalence of antimicrobial resistance among MDR uropathogens and to elucidate the molecular bases of plasmid-mediated resistance. Methods: Bacterial isolates were recovered from urine specimens of 150 out-patients with signs and symptoms of urinary tract infections (UTIs) at El-Demerdash Hospital, Cairo, Egypt. Standard methods were used for identification, antimicrobial suscep- tibility testing was performed according to CLSI guidelines. Results: Among the recovered isolates, 22.7% and 77.3% were Gram-positive, and negative, respectively. Of which; 43.3% were MDR with 60% harboring plasmids. Extended spectrum β-lactamase (ESBL) genes blaCTX-M, blaSHV, and blaTEM were detected on plasmids of 89.7%, 41%, and 84.6% of the tested isolates, respectively. The aminoglycoside resistance gene aac6’-Ib/aac-6’-Ib- cr was found on plasmids of 92.3% of the tested isolates followed by qnrS (92.3%), qnrB (46.2%), and qnrA (7.7%). The most prevalent quinolone efflux pump gene was oqxB (38.5%), followed by oqxA (20.5%), then qepA (10.3%). Conclusion: High levels of resistance to nitrofurans, β-lactam/β-lactamase inhibitor, cephalosporins, aminoglycosides, and fluoroquinolones were detected, and their use as empirical treatment for UTIs has become questionable. Keywords: ESBLs; qnR; plasmid-mediated; uropathgens; antibacterial resistance.