Abstract Background Antibiotic (ABX) treatment of uncomplicated urinary tract infection (uUTI) is often prescribed empirically which may lead to treatment failure (TF) and antimicrobial resistance (AMR). Suspected AMR may be assessed using a published AMR risk categorization framework. This study aimed to investigate the impact of high predicted risk of AMR on TF in female outpatients with uUTI. Methods Female outpatients aged ≥ 12 years with a uUTI diagnosis (Dx) between Jan 2018 and Sep 2022 were assessed retrospectively using Optum’s de-identified Electronic Health Record dataset. TF was defined as having a second oral ABX prescription (Rx), intravenous ABX, or emergency department/inpatient stay with a primary Dx of UTI ≤ 28 days after the first empiric oral ABX Rx for the uUTI Dx. Four validated AMR risk predictive models categorized patients as low or moderate (L/M) or high risk of isolate non-susceptibility to each of nitrofurantoin, sulfamethoxazole-trimethoprim, fluoroquinolones, and β-lactams, separately. Patients predicted to have high risk of isolate non-susceptibility to ≥ 1 ABX class were categorized as high AMR risk. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to compare TF in patients with L/M AMR risk vs high AMR risk and the effect of recurrent uUTI history on TF in high AMR risk patients was explored. Results Of 376,004 female outpatients with uUTI, 121,802 (32.4%) were categorized as high AMR risk (Table 1). Risk of TF was higher in patients with high AMR risk vs L/M AMR risk (21% vs 15%, adjusted RR [95% CI] = 1.21 [1.20–1.23]; p< 0.001; Table 2). TF risk increased with number of predicted high risk ABX classes, as patients with 1, 2, 3, and 4 predicted high risk ABX classes had unadjusted TF RRs of 1.23, 1.37, 1.71, and 2.01, respectively, vs those with L/M AMR risk (all p< 0.001; Table 2). TF rates were higher in patients with high AMR risk and recurrent UTI history vs L/M AMR risk and non-recurrent UTI (23.1% vs 14.6%, unadjusted RR [95% CI] = 1.58 [1.55–1.62]; Table 3). Conclusion Female uUTI outpatients with high predicted AMR risk to ≥ 1 oral ABX had a significantly greater risk of TF vs those with L/M predicted risk of AMR. These findings underscore the clinical importance of suspected AMR and history of UTI recurrence in empiric treatment decision-making for uUTI. Funding GSK study 219500 Disclosures Debra L. Fromer, MD, GSK: Advisor/Consultant|Johnson & Johnson/Janssen Pharmaceuticals: Advisor/Consultant Meghan Luck, PharmD, BCPS, GSK: Employee|GSK: Stocks/Bonds (Private Company) Malena Mahendran, MS, Analysis Group, Inc.: Employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Rose Chang, ScD, Analysis Group, Inc.: Employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Megan Pinaire, MPH, Analysis Group, Inc.: Employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Dar Alon, MS, Analysis Group, Inc.: Employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Mei Sheng Duh, MPH, ScD, Analysis Group, Inc.: Employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company) Jeffrey J. Ellis, PharmD, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company)
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