| Summary: | Urinary tract infections (UTIs) are among the most common bacterial infections in children, and <i>Escherichia coli</i> is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of <i>E. coli</i> isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of <i>E. coli</i>-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (<i>p</i> < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (<i>p</i> = 0.007). The prevalence of multidrug-resistant <i>E. coli</i> rose from 3.9% to 9.2% (<i>p</i> = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant <i>E. coli</i> among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.
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