Multi-drug resistant (MDR) Escherichia coli is one of the most prevalent gram-negative pathogenic bacteria. Human skin is the first barrier against different pathogens. The invasion of the destructed skin with such MDR E. coli cause serious wound infections. Treatment of these infections is very difficult due to the ability of the bacteria to utilize different resistance mechanisms. Production of extended spectrum β-lactamases is the most important mechanism as they confer resistance to almost used antibiotics. The study aimed to detect the prevalence blaCTX-M gene among MDR E. coli isolated from wound infections. In this study out of 150 wound specimens, 66 (44%) E. coli were isolated. Their susceptibility to different classes of antibiotics were tested by Kirby Bauer disk diffusion method. The isolates exhibited high resistance level to cefotaxime, ceftriaxone, ceftazidime and amoxicillin /clavulanic. Piperacillin/ Tazobactam and Azithromycin were found to be the most effective antibiotics. The ESBLs production was detected by combined disc method. Twenty-five isolates (37.87%) were found to be ESBLs producers. Their MARI ranged from 0.32 to 0.93. Out of the 25 ESBLs producers, 14 (56%) isolates were positive for blaCTX-M gene. Their MARI ranged from 0.57 to 0.89. In conclusion, the high prevalence of MDR ESBL producer E. coli sounds the alarm. There is a need to apply strict infection control and continuous antimicrobial surveillance studies.