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The present study was planned to isolate Escherichia coli from pneumonic and septicemic sheep and goats and to determine antimicrobial resistance (AMR) patterns of the isolates and evaluate them for the presence of extended-spectrum β-lactamase (ESBL) using the phenotypic and molecular methods. Pneumonic lung tissues and heart blood samples were collected by performing necropsy on sheep (n = 96) and goats (n = 08). The samples were processed and used for bacterial isolation. E. coli isolates (n = 58) including 53 from 34 sheep and 5 from 3 goats were recovered and identified by the cultural and biochemical characteristics and 16S rRNA sequencing. The isolates were tested to ascertain AMR pattern, plasmid features, and ESBL production. The highest rate of resistance (65.5%) was recorded against amoxicillin, enrofloxacin, norfloxacin, and ofloxacin. Eighteen (31%) out of 58 isolates showed the ESBL phenotype by combination disk assay. There was a variability in the number (1-5) and size (2 to >20 kb) of plasmids among isolates. Polymerase chain reaction (PCR) amplification revealed the presence of blaTEM (70.6%) and blaSHV (1.7%) genes. PCR specificity was confirmed by nucleotide sequencing. The present study indicates that the extraintestinal and multidrug-resistant (MDR) E. coli strains were associated with pneumonia and/or septicemia in sheep and goats. Therefore, thorough surveillance and monitoring of MDR bacteria are urgently needed to implement the infection control strategies and to restore the efficacy of available antibiotics. [ABSTRACT FROM AUTHOR]