A total of 648 diarrheagenic Escherichia coli (DEC) were isolated from calves (n = 219), lambs (n = 87), kids (n = 103), human (n = 193), and water (n = 46) samples. The presence of enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), and shigatoxigenic E. coli (STEC) was confirmed by PCR-based detection of the Shiga toxin, intimin, hemolysin, and enterotoxin genes. All the isolates were tested for antimicrobial resistance (AMR) by disc diffusion assay. Extended-spectrum β-lactamase (ESBL), carbapenemase, and metallo-beta-lactamase production were determined by double-disk synergy test, modified Hodge test, and combined disk test assays. AMR genes (bla_TEM, bla_SHV, bla_CTX-M, bla_CMY-2, bla_NDM, bla_KPC, bla_VIM, and bla_IMP) were detected by PCR using specific primers. Majority of the isolates from human and water exhibited resistance (>80%) against amoxicillin, ampicillin, aztreonam, cefotaxime, cefixime, gentamicin, ceftazidime, and cefalexin, and against imipenem (70.98%), doripenem (70.47%), and ertapenem (60.62%). Bovine isolates were sensitive to carbapenems. Many isolates (5.75-24.35%) from human, water, calves, kids, and lambs were multidrug resistant (MDR), with resistance against three or more classes of antimicrobials. A total of 170/648 (26.23%) isolates were classified as STEC (9.88%), EPEC (4.32%), and ETEC (12.04%). The AMR genes, including bla_TEM, bla_CMY2, bla_CTX-M, and bla_SHV were detected in the E. coli from all sources. but bla_NDM and bla_KPC were detected only in the isolates from human and water. Three STEC isolates from human origin possessed multiple ESBLs, carbapenemase and metallo-beta-lactamase genes reported for the first time. ESBLs producing EPEC and ETEC in lambs and kids are also reported under this study. Presence of MDR-DEC in domestic animals and common potable water poses public health concern in this region.

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