Prospective Evaluation of ESBL Risk Factors and Appropriateness of Empirical Therapy in Hospitalized Patients with Community-Onset Pyelonephritis

Background/Objectives: The rising prevalence of extended-spectrum beta-lactamase (ESBL)-producing pathogens has emerged as a significant challenge in the treatment of pyelonephritis. This study aims to determine the frequency of ESBL-producing agents in hospitalized patients with pyelonephritis, identify associated risk factors, and assess the appropriateness of empirical antimicrobial therapy. Methods: This prospective study included patients hospitalized with pyelonephritis in the Infectious Diseases Clinic of Ankara Training and Research Hospital between 1 October 2022 and 29 February 2024. Demographic features, comorbidities, urinary system pathologies, history of urinary tract interventions, hospitalization more than one month prior, antibiotic use within the previous three months, and prior urinary tract infections were compared between patients infected with ESBL-producing and non-ESBL-producing organisms. Antimicrobial susceptibility profiles and the appropriateness of empirical treatments were evaluated. Statistical analyses were performed using SPSS version 25.0, with p < 0.05 considered statistically significant. Results: Escherichia coli (n = 142) and Klebsiella spp. (n = 43) were isolated in 180 of 204 patients. ESBL positivity was detected in 95 patients (52.7%). In the multivariate logistic regression analysis, male sex (p = 0.038) and hospitalization more than one month prior (p = 0.016) were identified as independent risk factors for ESBL positivity, while prior antibiotic use in the last three months showed a borderline association (p = 0.055) and did not reach statistical significance. ESBL production was not associated with prolonged hospitalization; however, bacteremia significantly increased length of stay (p < 0.001). Antimicrobial susceptibility rates were markedly lower in the ESBL-positive group. The appropriateness of empirical therapy was also significantly reduced, with piperacillin–tazobactam being the most frequently inappropriate agent due to high resistance rates and unnecessary broad-spectrum use. Conclusions: ESBL-producing pathogens were highly prevalent among hospitalized patients with pyelonephritis. The low appropriateness of empirical therapy in ESBL-positive cases underscores the need for careful evaluation of ESBL risk factors prior to treatment initiation, as ESBL rates may approach 50%.