| Summary: | <b>:</b> The aim of this study was to investigate the annual incidence of Escherichia coli isolates in urinary tract infections (UTIs) and the antimicrobial resistance of the third-generation cephalosporin (3GCs) to E. coli, including the factors associated with the resistance in hospitalized children in Taiwan. A large electronic database of medical records combining hospital admission and microbiological data during 2004–2018 was used to study childhood UTIs in Taiwan. Annual incidence rate ratios (IRR) of <i>E. coli</i> in children with UTIs and its resistant rate to the 3GCs and other antibiotics were estimated by linear Poisson regression. Factors associated with <i>E. coli</i> resistance to 3GCs were assessed through multivariable logistic regression analysis. <i>E. coli</i> UTIs occurred in 10,756 unique individuals among 41,879 hospitalized children, with 92.58% being community associated based on urine culture results reported within four days after the hospitalization. The overall IRR <i>E. coli</i> UTI was 1.01 (95% confidence interval (CI) 0.99–1.02) in community-associated (CA) and 0.96 (0.90–1.02) in healthcare-associated infections. The trend in 3GCs against <i>E. coli </i>increased (IRR 1.18, 95% CI 1.13–1.24) over time in CA-UTIs. Complex chronic disease (adjusted odds ratio (aOR), 2.04; 95% CI, 1.47–2.83) and antibiotics therapy ≤ 3 months prior (aOR, 1.49; 95% CI, 1.15–1.94) were associated with increased risk of 3GCs resistance to <i>E. coli</i>. The study results suggested little or no change in the trend of <i>E. coli</i> UTIs in Taiwanese youths over the past 15 years. Nevertheless, the increase in 3GCs-resistant <i>E</i><i>.</i><i> coli</i> was substantial. Interventions for children with complex chronic comorbidities and prior antibiotic treatment could be effective in reducing the incidence of 3GCs-resistant <i>E</i><i>.</i><i> coli</i> in CA-UTIs in this region and more generally.
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