Urinary Tract Infections in a Single-Center Bulgarian Hospital: Trends in Etiology, Antibiotic Resistance, and the Impact of the COVID-19 Pandemic (2017–2022)

<b>Background</b>: Urinary tract infections (UTIs) are among the most common hospital- and community-acquired infections, creating a substantial healthcare burden due to recurrence, complications, and rising antimicrobial resistance. Accurate diagnosis and timely antimicrobial therapy are essential. This study aimed to identify trends in the etiology, treatment, and resistance patterns of UTIs through a retrospective analysis of urine isolates processed at the Laboratory of Microbiology at University Hospital St. George in Plovdiv, the largest tertiary care and reference microbiology center in Bulgaria, between 2017 and 2022. <b>Materials and Methods</b>: A retrospective single-center study was performed at the hospital's Microbiology Laboratory. During the study period, 74,417 urine samples from 25,087 hospitalized patients were screened with the HB&L UROQUATTRO system. Positive specimens were cultured on blood agar, Eosin-Methylene Blue, and chromogenic media. Identification was performed using biochemical assays, MALDI-TOF MS, and the Vitek 2 Compact system. Antimicrobial susceptibility testing included disk diffusion, MIC determination, broth microdilution (for colistin), and Vitek 2 Compact, interpreted according to EUCAST standards. Descriptive analysis and temporal resistance trends were evaluated with regression models, and interrupted time-series analysis was applied to assess COVID-19-related effects. <b>Results</b>: Out of 10,177 isolates, Gram-negative bacteria predominated (73%), with <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, and <i>Proteus mirabilis</i> as the leading pathogens. Among Gram-positives, <i>Enterococcus faecalis</i> was the most frequent. In the post-COVID-19 period, ESBL production increased in <i>E. coli</i> (34-38%), <i>K. pneumoniae</i> (66-77%), and <i>P. mirabilis</i> (13.5-24%). Carbapenem resistance rose in <i>K. pneumoniae</i> (to 40.6%) and <i>P. aeruginosa</i> (to 24%), while none was detected in <i>E. coli</i>. Colistin resistance increased in <i>K. pneumoniae</i> but remained absent in <i>E. coli</i> and <i>P. aeruginosa</i>. High-level aminoglycoside resistance in <i>E. faecalis</i> was stable (~70%), and vancomycin resistance in <i>E. faecium</i> rose from 4.6% to 8.9%. <b>Conclusions</b>: Both community- and hospital-acquired UTIs in Southeastern Bulgaria are increasingly linked to multidrug-resistant pathogens, particularly ESBL-producing and carbapenem-resistant <i>Enterobacterales</i>. Findings from the region's largest referral center highlight the urgent need for continuous surveillance, rational antibiotic use, and novel therapeutic approaches.