Antimicrobial Treatment Ameliorates Delirium-like Phenotypes in Murine Model of Urinary Tract Infection

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New research conducted at Cedars-Sinai Medical Center in Los Angeles, California, reveals that antimicrobial treatment can alleviate delirium-like symptoms in mice induced with urinary tract infections (UTI). The study, published in Translational Psychiatry, suggests that this finding could have significant implications for the treatment of delirium in humans, particularly in cases where UTI is suspected.

Key Takeaways:

  • The study tested the hypothesis that UTI induces delirium-like phenotypes that are mitigated by antimicrobial therapy (ABX).
  • Researchers induced UTI in female C57BL/6 J mice aged 4-5 months and randomized them to receive either one dose of ceftriaxone 600 mg/kg (n = 23) or saline (n = 21) one day after induction.
  • Delirium-like behaviors were assessed using Open Field, Elevated Plus Maze, and Y-maze tests, while neurostructural changes were evaluated using neuronal cleaved caspase-3 (CC3) and interleukin-6 (IL-6) via immunohistochemistry.
  • Compared to vehicle-treated mice, ABX mice with UTI demonstrated decreased time in the periphery of the Open Field maze, decreased time in the closed arms of the Elevated Plus Maze, and increased spontaneous alternations in Y-maze.
  • These behavioral changes were accompanied by significantly lower frontal/hippocampal CC3 and IL-6 levels in ABX-treated mice compared to vehicle-treated mice.
  • The study concluded that 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.

Statistics:

  • 23 mice received one dose of ceftriaxone 600 mg/kg
  • 21 mice received saline
  • Statistical significance was achieved for the following behavioral changes:

+ Decreased time in the periphery of the Open Field maze (p = 0.017)

+ Decreased time in the closed arms of the Elevated Plus Maze (p = 0.013)

+ Increased spontaneous alternations in Y-maze (p = 0.015)

  • Statistical significance was also achieved for the neurostructural changes:

+ Frontal/hippocampal CC3 levels in ABX-treated mice (p = 0.0038, p = 0.0003, respectively)

+ IL-6 levels in ABX-treated mice (p = 0.015)

Sources:

  • Antimicrobial treatment ameliorates delirium-like phenotypes in a murine model of urinary tract infection. Translational Psychiatry, 2025;15(1):360.
  • NewsRx. New Data from Cedars-Sinai Medical Center Illuminate Findings in Delirium (Antimicrobial treatment ameliorates delirium-like phenotypes in a murine model of urinary tract infection). Mental Health Weekly Digest. October 20, 2025; p 477.