A Rat Model of Ascending Uncomplicated Urinary Tract Infection for Anti-Infective Efficacy Studies

Urinary tract infections (UTIs) are among the most prevalent bacterial infections worldwide and contribute substantially to antimicrobial resistance, highlighting the need for robust preclinical models to support development of novel anti‑infective therapies. Although mouse models dominate UTI research, anatomical and technical constraints can limit translational pharmacokinetic and pharmacodynamic (PK/PD) studies, particularly for intravenously administered agents. Here, we describe and validate an ascending model of uncomplicated UTI in adult female Wistar rats that enables reproducible bladder and kidney infection and supports comprehensive treatment evaluation. Transurethral catheterization was used to inoculate the bladder with the well‑characterized uropathogenic Escherichia coli strain CFT073. Compared with Sprague Dawley rats, Wistar rats exhibited more stable infection kinetics and lower intra‑group variability and were therefore selected for model optimization. Enrichment of type 1 fimbriae expression significantly enhanced bladder colonization, urinary bacterial shedding, and ascending infection of the kidneys. Using this optimized model, a single intravenous dose of ciprofloxacin produced rapid bactericidal activity within two hours of treatment and sustained efficacy, with three to four log reductions in bacterial burdens in urine, bladder, and kidneys at twenty‑four hours post‑treatment. Histopathological analysis demonstrated infection‑associated immune cell infiltration and tissue edema in the bladder, both of which were markedly reduced following antibiotic treatment. Multiplex cytokine profiling of bladder tissue revealed a localized inflammatory response characterized by increased IL‑1α and MIP‑3α during infection, with broader pro‑inflammatory cytokine induction observed following ciprofloxacin administration. Together, these findings establish a reproducible, physiologically relevant rat model for integrated preclinical evaluation of intravenous antimicrobials targeting UTIs.