(1) Background: Urinary tract infections (UTIs) are among the most common infections in the pediatric population. This study aimed to analyze the urine culture results and antimicrobial patterns over the last 5 years in children diagnosed with UTI. (2) Methods: Retrospective analysis of medical records of 242 patients hospitalized in the Pediatric Nephrology Department diagnosed with a UTI in the years 2018–2022. (3) Results: The most common causative agent was E. coli, responsible for 64% of UTIs, followed by Klebsiella spp. (16%), Pseudomonas spp. (6%), Enterobacter spp. (4%), Proteus spp. (4%), and Enterococcus spp. (3%). Non-E. coli UTIs were significantly more frequently observed in patients with congenital anomalies of the kidney and urinary tract or neurogenic bladder and patients receiving antibiotic prophylaxis. For the whole study period, 32% of E. coli were resistant to amoxicillin/clavulanic acid, 23.3% to trimethoprim/sulfamethoxazole, 12.2% to ciprofloxacin, and 4.4% to nitrofurantoin. During 2018–2022, the prevalence of E. coli resistant to amoxicillin/clavulanic acid varied from 16.7% to 41.2%, and resistance to cefuroxime increased four times (from 4% in 2018 to 16.7% in 2022). Starting in 2021, all isolated E. coli strains were classified as susceptible-increased exposure or resistant to cefuroxime. (4) Conclusion: Managing pediatric UTIs remains challenging in clinical practice. The choice of optimal empiric treatment should be considered following local recommendations and individual risk factors assessment and require careful dosage adjustment. Observed changes in antimicrobial resistance indicated the need for frequent updating of local recommendations for the management of pediatric patients with UTIs.