Extra-intestinal pathogenic Escherichia coli (ExPEC), a predominant Gram-negative bacterial pathogen, express a wide range of virulence factors and is responsible of several diseases including urinary tract infections (UTI), nosocomial pneumonia, bacteremia, and neonatal meningitis. ExPEC isolates are often multidrug resistant (MDR) and clones producing extended-spectrum beta-lactamases (ESBL) are increasingly reported all over the world.Seventy-eight clinical ExPEC strains were selected for this study. The majority was from UTIs (n=51), while the rest (n=27) was from pus, sputum, bronchial fluid and vaginal samples (non-uropathogenic ExPEC). Interestingly, 49 out of the 78 ExPEC isolates where considered as community-acquired (CA) and 29 hospital-acquired (HA) bacteria. Antibiotic susceptibility testing was performed using the Kirby-Bauer disc diffusion method. Standard polymerase chain reaction (PCR) was used to screen major ESBL genes (blaCTX-M, blaOXA-1, blaTEM, blaSHV) and blaCTX-M variants (blaCTX-M-1, blaCTX-M-9, blaCTX-M-15, blaCTX-M-25).All the ExPEC strains were resistant to ampicillin, ticarcillin, amoxicillin/clavulanic acid combination, cefalotin, cefotaxime, ceftazidime, cefepime and aztreonam, but showed a high susceptibity to fosfomycin (98.7%, n = 77), ertapenem (96.2%, n = 75), and imipenem (100%). Moreover, isolates harbored at least one ESBL gene, including blaCTX-M (98.7%), blaOXA-1 (78.2%), blaTEM (44.9%) and blaSHV (3.8%). The CTX-M variants were also found with the predominance of blaCTX-M-1 (90.9%) and blaCTX-M-15 (90.9%) followed by blaCTX-M-9 (11.7%), while blaCTX-M-25 was not detected.Despite the resistance to most of the tested antibiotics, ExPEC isolates showed fortunately a good susceptibility to fosfomycin and carbapenems. blaCTX-M (blaCTX-M1, blaCTX-M15) and blaOXA-1 seem to be E. coli major ESBL genes circulating in Senegal. No significant difference was noted when comparing prevalence of ESBL genes detected from CA and HA strains, and from UPEC and non-uropathogenic ExPEC. The high level of resistance to antimicrobials observed stresses the need of establishing an epidemiological surveillance of antimicrobial resistance in both community and hospital settings.