| Summary: | Household cats have been identified as potential antimicrobial resistance (AMR) reservoirs, and the extended-spectrum <i>β</i>-lactamases (ESBL) producing <i>E. coli</i> circulating among cats has been more frequently reported globally, but the factors linked to its colonization remain poorly understood. Thus, the objectives of this study were to determine <i>E. coli</i> shedding and the occurrence of multidrug resistant (MDR)- and ESBL-producing <i>E. coli</i>, as well as to determine risk factors associated with colonization of MDR and ESBL-producing <i>E. coli</i> isolated from both healthy and diseased cats in the Eastern Province of Saudi Arabia. In a cross-sectional study, 2000 swabs were collected from five anatomical regions (anus, skin, ear canal, nares, and conjunctival sac) of 209 healthy and 191 diseased cats that were admitted to a veterinary clinic in the Eastern Province of Saudi Arabia. In addition, each cat owner filled out a questionnaire about their cat’s demographics, management, health status, and antimicrobial usage. <i>E. coli</i> was detected in 165 (41.3%) of all cats, including 59 (28.2%) healthy and 106 (55.5%) diseased cats. In total, 170 <i>E. coli</i> isolates were found in healthy (35.3%) and diseased (64.7%) cats. Susceptibility testing revealed that 123 (72.4%) of the <i>E. coli</i> isolates were resistant to at least one of the tested antimicrobials. Overall, 17.6% (30/170) of <i>E. coli</i> isolates were MDR, with 10 (5.9%) and 20 (11.8%) isolates found in healthy and diseased cats, respectively. However, only 12 (7.1%) <i>E. coli</i> isolates were resistant to cefotaxime and harbored the <i>bla</i><sub>CTX-M</sub> gene (ESBL-producer), with seven (4.1%) in healthy and five (2.9%) in diseased cats. Risk factor analysis showed that the odds of MDR and ESBL-producing <i>E. coli</i> were (20 and 17) and (six and eight) times higher when the family and cats were previously treated with antimicrobials, respectively. The presence of a child in the cat’s family was also linked to an increased risk of MDR <i>E. coli</i> colonization (OR = 3.4). In conclusion, a high frequency of MDR and ESBL-producing <i>E. coli</i> was detected among healthy and diseased cats in Saudi Arabia, raising concerns about transmission to humans and supporting the need of a “One Health” approach to address the potential threats of cats as AMR reservoirs.
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