Challenges in the Treatment of Urinary Tract Infections: Antibiotic Resistance Profiles of Escherichia coli Strains Isolated from Young and Elderly Patients in a Southeastern Romanian Hospital

<b>Background/Objectives</b>: Urinary tract infections (UTIs) represent a significant public health challenge, with <i>Escherichia coli</i> being the primary causative pathogen. The rise in antimicrobial resistance (AMR), further intensified by shifts in antibiotic prescribing practices during and after the COVID-19 pandemic, poses substantial difficulties in treatment optimization and clinical management. <b>Methods</b>: This retrospective study analyzed 644 <i>E. coli</i> strains from urine samples collected in a southeastern Romanian hospital during two periods: pre-pandemic (2018-2019, N = 361) and post-pandemic (2023-2024, N = 283). Antimicrobial susceptibility was assessed using the VITEK automated system for key antibiotic classes. <b>Results</b>: A significant increase in fluoroquinolone resistance was observed, especially for ciprofloxacin (<i>p</i> = 0.02), alongside rising ceftriaxone resistance (<i>p</i> = 0.004), suggesting the spread of ESBL-producing strains. Resistance to trimethoprim/sulfamethoxazole, ampicillin, and amoxicillin/clavulanic acid remained high, limiting their empirical use. Carbapenem resistance was low (<i>p</i> > 0.1), while nitrofurantoin and fosfomycin retained high efficacy (<i>p</i> = 0.26 and <i>p</i> = 0.64). <b>Conclusions</b>: The post-pandemic period showed a concerning rise in resistance to fluoroquinolones and third-generation cephalosporins, highlighting the need for stricter antimicrobial stewardship. Carbapenems remain effective for severe infections, while nitrofurantoin and fosfomycin are reliable first-line options for uncomplicated UTIs. Continuous AMR surveillance is essential to optimize treatment and curb multidrug-resistant strains.