BackgroundAlthough uncomplicated urinary tract infections (uUTIs; occurring in female patients without urological abnormalities or history of urological procedures or complicating comorbidities) are one of the most common community infections in the United States (US), limited data are available concerning associations between antibiotic resistance, suboptimal prescribing, and the economic burden of uUTI. We examined the prevalence of suboptimal antibiotic prescribing and antibiotic resistance and its effects on healthcare resource use and costs.MethodsThis retrospective cohort study utilized electronic health record data from a large Mid-Atlantic US integrated delivery network database, collected July 2016–March 2020. Female patients aged ≥ 12 years with a uUTI, who received ≥ 1 oral antibiotic treatment within ± 5 days of index uUTI diagnosis, and had ≥ 1 urine culture with antimicrobial susceptibility test, were eligible for inclusion in the study. The study examined the proportion of antibiotics that were inappropriately or suboptimally prescribed among patients with confirmed uUTI, and total healthcare costs (all-cause and UTI-related) within 6 months after a uUTI, stratified by antibiotic susceptibility and/or inappropriate or suboptimal treatment. Patient outcomes were assessed after 1:1 propensity score matching of patients with antibiotic-susceptible versus not-susceptible isolates and then by other covariates (e.g., demographics and recent healthcare use). A similar propensity score calculation was used to analyze the effect of inappropriate/suboptimal treatment on health outcomes. Costs were adjusted to 2020 US dollars ($).ResultsAmong 2565 patients with a uUTI included in the analysis, the most commonly prescribed antibiotics were nitrofurantoin (61%), trimethoprim-sulfamethoxazole (19%), and ciprofloxacin (15%). More than one-third of the sample (40.2%) had isolates that were not-susceptible to ≥ 1 antibiotic indicated for treating patients with uUTI. Two-thirds (66.6%) of study-eligible patients were prescribed appropriate treatment; 29.9% and 11.9% were prescribed suboptimal and/or inappropriate treatment, respectively. Inappropriate or suboptimally prescribed patients had greater all-cause and UTI-related costs compared with appropriately prescribed patients. Differences were most striking among patients with antibiotic not-susceptible isolates.ConclusionsThese findings highlight how the increasing prevalence of antibiotic resistance combined with suboptimal treatment of patients with uUTI increases the burden on healthcare systems. The finding underlines the need for improved prescribing accuracy by better understanding regional resistance rates and developing improved diagnostic tests.