2026 Southeastern Residency Conference

Background: Acute pyelonephritis is a common and potentially serious bacterial infection of the upper urinary tract that frequently results in emergency department (ED) visits and hospitalizations. The most recent Infectious Diseases Society of America (IDSA) guidelines for the management of complicated urinary tract infections (cUTI), include levofloxacin, ciprofloxacin, and sulfamethoxazole-trimethoprim as first line options. Rising antimicrobial resistance among Enterobacterales rases concern for their effectiveness. Thus, clinicians often turn to oral beta-lactams. While well tolerated, their efficacy for pyelonephritis is less established due to lower renal tissue concentrations and variable oral bioavailability. However, recent evidence indicates favorable outcomes with oral beta-lactams. 
Additionally, given the increasing prevalence of extended-spectrum beta-lactamases (ESBLs), understanding the impact of antibiotic selection on the development of future resistance is essential to optimizing antibiotic selection.  
This study aimed to evaluate the comparative effectiveness and downstream resistance outcomes of oral beta-lactam therapy versus first-line agents for the treatment of acute pyelonephritis among adults discharged from the ED. 
 
Methodology: This was a multi-site, retrospective, observational cohort study comparing clinical outcomes and the emergence of ESBL organisms in patients treated for pyelonephritis using first-line agents versus beta-lactam antibiotics. Patients 18 years or older with an ICD-10 code diagnosis of pyelonephritis, a positive urine culture, and an outpatient antibiotic prescription for at least 7 days during the study period from April 1, 2024, to July 8, 2025, were included. Patients were excluded if they had polymicrobial cultures, prior ESBL-producing organism within 3 months, more than one dose of intravenous antibiotics, diagnoses of prostatitis, orchitis, epididymitis, or pregnancy, and patients requiring change of prescription from index visit. The primary outcome was rate of treatment failure within 30 days of the initial ED visit; secondary outcomes included antibiotic selection, dosing, duration, and rates of ESBL emergence.  
Data collection included baseline characteristics such as age, sex, comorbidities, and urine culture resistance patterns within 3 months prior to the ED visit. Statistical analysis was conducted using Pearson’s Chi-squared tests for categorical variables, Student’s t-tests for continuous variables, and univariate regression for association between antibiotic choice and treatment failure. 
Results: A total of 1,396 patients were included in the study between April 2025 and July 2025, 792 patients in the beta-lactam and 604 in the first-line therapy group. The most common reason for exclusion was a change in antibiotic therapy following identification of resistance to the initial agent. 
Patient characteristics and demographics were well balanced between the groups. Most patients were female (89%), non-Hispanic or Latino (78%), and 46% received intravenous antibiotics in the emergency department. The most frequently identified baseline pathogen was Escherichia coli (74%), followed by Klebsiella species (7.6%). 
The primary outcome, treatment failure, occurred in 78 patients (5.6%), including 53 (6.7%) in the beta-lactam group and 25 (4.1%) in the first-line group (p = 0.040). Guideline appropriate dosing was observed in 477 patients (64%) in the beta-lactam group compared to 571 patients (99%) in the first-line group (p < 0.001). Cefdinir was prescribed 142 (10.8%) times but is not recommended in the IDSA guidelines for pyelonephritis. The most frequently guideline non-compliant therapy was cephalexin, which was appropriately dosed in only 38% (14/68) of cases. ESBL emergence was rare, occurring in 5 patients (0.4%), with 4 cases in the beta-lactam group and 1 case in the first-line group (p = 0.4). 
Conclusions: Treatment failure was more frequent in the beta-lactam group.  This finding is potentially attributable to inappropriate antibiotic selection and suboptimal dosing. Specifically, the overuse of cefdinir and underdosing of cephalexin likely contributed to these treatment failures. Additionally, our investigation did not demonstrate a significant association between antibiotic choice and the development of ESBL.