Antimicrobial treatment ameliorates delirium-like phenotypes in a murine model of urinary tract infection.

ABSTRACT: Practice guidelines recommend withholding antimicrobial therapy (ABX) in delirious patients with suspected urinary tract infection (UTI) who do not endorse classic genitourinary symptoms, citing both a lack of a causal relationship between bacteriuria and delirium and benefit from ABX. In this study, we tested the hypothesis that UTI induces delirium-like phenotypes that are mitigated by ABX. Escherichia coli (CFT073) UTI was induced in female C57BL/6 J mice aged 4-5 months. Mice were randomized to receive one dose of ceftriaxone 600 mg/kg (n = 23) or saline (n = 21) one day after induction of UTI. Delirium-like behaviors were assessed using Open Field, Elevated Plus Maze, and Y-maze, while neurostructural changes were evaluated using neuronal cleaved caspase-3 (CC3) and interleukin-6 (IL-6) via immunohistochemistry. Plasma IL-6 was quantified using ELISA. Compared to vehicle-treated mice, ABX mice with UTI demonstrated: 1) decreased time in the periphery of the Open Field maze (p = 0.017), 2) decreased time in the closed arms of the Elevated Plus Maze (p = 0.013), and 3) increased spontaneous alternations in Y-maze (p = 0.015). These behavioral changes were accompanied by significantly lower frontal/hippocampal CC3 (p = 0.0038, p = 0.0003, respectively) and IL-6 (p = 0.015) levels in ABX- compared to vehicle-treated UTI mice. ABX significantly lowered plasma IL-6 compared to vehicle-treated UTI mice (p < 0.01). This study suggests a causal relationship between UTI and functional/neurostructural delirium-like phenotypes that are attenuated with ABX. These findings provide strong rationale for a randomized clinical trial to evaluate the role of ABX in patients with delirium as the isolated presumed sign of UTI.

SUBMITTER: Winzey KD 

PROVIDER: S-EPMC12501002 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature