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Antimicrobial resistance (AMR) is a global threat that requires serious attention, particularly when it is developed against colistin, which is considered one of the 'last resort' antibiotics in the poultry industry. This study aimed to investigate the AMR profile of Enterobacteriaceae isolates from different poultry species, detect colistin resistance and investigate the existence of mcr genes in multi and extreme-resistant isolates. A total of 233 birds, chickens, ducks, turkeys, and quails, of various ages and breeds were collected from several localities of the Sharkia governorate and analyzed bacteriologically. The disc diffusion and E-test assays scrutinized the patterns of antibiotic, multidrug-resistant (MDR), and colistin resistance. The PCR assay was carried out to detect the mcr variants. Bacteriological examination revealed the incidence of 42.3% (99/233) of different Enterobacteriaceae members with a high predominance of E. coli, Salmonella, and Klebsiella species. Disc diffusion findings disclosed that 78.78% of isolates were resistant to colistin but E-test detected 19.19% only. Observed colistin resistance was strongly linked to the distribution of plasmid mcr-operons. The mcr 1, 2, 3, 4, and 7.1 genes were detected in 42.1, 63.15, 57.89, 52.63, and 47.36% of the phenotypic resistant isolates, and about 36.84% harbored at least four mcr clusters. However, the mcr5 gene was not discovered. The statistical assessment revealed a significant association between colistin resistance and MDR (p≤0.05). Moreover, there was a strong correlation between Mcr-abundance and doxycycline, fosfomycin, beta-lactams, imipenem, and tobramycin resistances. In conclusion, this study highlights the alarming occurrence of colistin-resistant Enterobacteriaceae in various poultry aspects. An urgent strategy must be adopted to avert the spread of this phenomenon. [ABSTRACT FROM AUTHOR]