2026 Southeastern Residency Conference

Title: Effectiveness of Amoxicillin-Clavulanate for the Treatment of Extended-Spectrum β-Lactamase-producing Enterobacterales (ESBL-E) Urinary Tract Infection

Author: Haseeb Ahmed, Nicholas Rosen, Ryan Tilton, Olivia Randazza, John Williamson, Charles Hartis, Michael E DeWitt, Alexandria Taylor, Jennifer J Wenner, Mary Banoub

Background: Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, with Enterobacterales being the predominant pathogens. The rise in prevalence of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) has led to increased antimicrobial resistance and recurrence rates. This prompts evaluation of alternative treatments such as amoxicillin-clavulanate, in which clavulanate may restore amoxicillin activity against common ESBL enzymes. The IDSA 2024 Antimicrobial-Resistant Gram-Negative guidelines recommend against its use but fail to cite high-quality evidence studying its efficacy in UTI caused by ESBL-E. Other studies, limited by small sample size, suggest clinical efficacy of amoxicillin-clavulanate in the treatment of UTI caused by ESBL-E. This study attempts to bolster the pool of data showing amoxicillin-clavulanate can be as effective as standard of care (SOC) antibiotics for treatment of UTI caused by ESBL-E.

Methods: This multi-site, retrospective cohort study is approved by the Institutional Review Board. Adult patients (≥18 years) with either uncomplicated or complicated UTI with a urine culture positive for ESBL-E (confirmed with susceptibility testing) treated between April 1, 2024, and July 1, 2025, at Atrium Health Wake Forest Baptist facilities were included. Patients must have received at least 72 hours of amoxicillin-clavulanate or SOC therapy. Patients were excluded if they had concurrent bacterial infections, polymicrobial urine cultures, a previous UTI within 90 days already captured in the dataset, anatomic urinary tract abnormalities or instrumentation, renal abscesses, prostatitis, receive in-vitro active antibiotic lead-in therapy for >50% of treatment duration, were immunosuppressed or use methenamine or antibiotics for prophylaxis. The primary endpoint is clinical failure within 90 days, defined as retreatment with antibiotics and either recurrence of UTI symptoms or a repeat urine culture positive for the same organism as the index infection. Secondary endpoints include time to clinical failure and recurrence of resistant organisms (carbapenem-resistant Enterobacterales, SOC-resistant, or amoxicillin-clavulanate-resistant strains) within 90 days. Chi-square or Fisher’s exact tests tested categorical variables, and t-tests or Mann-Whitney U tests will test continuous variables. Kaplan-Meier survival analysis and Cox regression modeling will assess time-to-event outcomes, and multivariable analysis will be used to identify patient factors associated with clinical failure.

Results: A total of 447 patients were screened, of whom 274 patients met inclusion criteria and were analyzed. Fifty-four patients were included in the amoxicillin-clavulanate group, while 220 patients were included in the SOC group. No statistically significant difference was observed in the primary outcome of treatment failure between the SOC and amoxicillin-clavulanate groups (p = 0.11). Patients with prior history of ESBL infection had more than twice the odds of treatment failure (OR 2.09; p = 0.04), a finding that remained significant after adjustment for antibiotic selection and type of UTI (OR 2.11, p = 0.047). Additionally, the use of sulfamethoxazole-trimethoprim for treatment of the index infection was associated with an 82% reduction in clinical failure compared to amoxicillin-clavulanate (p = 0.01).

Conclusions: Among patients treated with antibiotics for urinary tract infection caused by ESBL-producing Enterobacterales species, we were unable to detect a difference in treatment failure within 90 days between amoxicillin-clavulanate and SOC. This indicates that within the limits of this study, amoxicillin-clavulanate may have comparable effectiveness to other agents used to treat urinary tract infections caused by these resistant organisms.