BackgroundIncreasing prevalence of antimicrobial resistance (AMR), including multidrug resistance (MDR), amongEscherichia coli(E.coli) makes treatment of uncomplicated urinary tract infection (uUTI) difficult. We assessed risk factors for fluoroquinolone (FQ)-not-susceptible (NS) and MDRE.coliamong US female outpatients.MethodsThis retrospective cohort study utilized data from female outpatients aged ≥ 12 years withE.colipositive urine culture and oral antimicrobial prescription ± 1 day from index. We assessed patient-level factors within 90 and 91–360 days prior to index as predictors of FQ NS (intermediate/resistant) and MDR (NS to ≥ 1 drug across ≥ 3 classes)E.coli: age, prior oral antimicrobial dispensing, prior AMR phenotypes, prior urine culture, and prior hospitalization.ResultsAmong 1,858 outpatients with urine-isolatedE.coli, 369 (19.9%) had FQ NS and 59 (3.2%) had MDR isolates. After multivariable adjustment, independent risk factors (p< 0.03) for FQ NSE.coliwere older age, prior FQ NS isolates, prior dispensing of FQ, and dispensing of any oral antibiotic. Independent risk factors (p< 0.02) for MDR were prior extended-spectrum β-lactamase-producing isolates (ESBL+), prior FQ dispensing, and prior oral antibiotic dispensing.ConclusionsIn women with uUTI due toE.coli, prior dispensing of FQ or any oral antibiotic within 90 days predicted FQ NS and MDR urineE.coli. Prior urine culture with FQ NS isolates and older age were predictive of FQ NSE.coli. Prior ESBL+ was predictive of MDRE.coli. These data could help identify patients at risk for AMRE.coliand inform empiric prescribing.