Risk Factors for Empiric Treatment Failure in US Female Outpatients with Uncomplicated Urinary Tract Infection: an Observational Study

Background: Treatment failure (TF) in uncomplicated urinary tract infection (uUTI) increases disease burden and risk of antimicrobial resistance. Identification of risk factors for TF could inform empiric treatment decisions and reduce suboptimal outcomes. Objective: To evaluate the incidence of TF to empirically prescribed oral antibiotics and identify risk factors for TF in females with uUTI in the United States (US). Design: This retrospective cohort study used Optum’s de-identified Electronic Health Record dataset (January 2017–September 2022). Patients: Eligible female patients aged ≥ 12 years had ≥ 1 diagnosis of urinary tract infection (UTI) in an outpatient ambulatory/emergency department (ED) setting, ≥ 1 empiric oral antibiotic prescription, and no evidence of complicated UTI (cUTI). Main Measures: TF was defined as having a new/repeat oral antibiotic prescription, IV antibiotic administration or acute UTI diagnosis ≤ 28 days following initial empiric oral antibiotic prescription​. Risk factors of TF were selected using LASSO and reported using adjusted risk ratios (aRR) and 95% CIs. Key Results: Of 376,004 patients with uUTI, 62,873 (16.7%) experienced TF. Incidence of TF was highest in patients with history of antibiotic TF (33.9%) or fosfomycin prescription (30.1%). Significant risk factors of TF included ≥ 3 prior antibiotic prescriptions (aRR [95% CI]: 1.60 [1.56–1.64]); fosfomycin prescription (1.60 [1.38–1.86]); uUTI diagnosis in ED (1.49 [1.46–1.52]), Southern US residence (1.37 [1.35–1.40]), age ≥ 75 years (1.35 [1.29–1.41]), recurrent UTI (1.12 [1.10–1.14]) and obesity (1.06 [1.04–1.08]). Conclusions: Incidence of TF to empirically prescribed oral antibiotics for uUTI is considerable. Prior infections requiring antibiotic prescription and location of care are key risk factors for TF in female outpatients with uUTI. Knowledge of these TF risk factors can inform shared-decision making and supplement existing guidance on uUTI treatment.