Chronic uropathogenic Escherichia coli infections in adolescence: in vitro analysis of clinical isolates, multidrug resistance, and in vivo hippocampal cognitive impacts.

Chronic urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are a major global health issue, with emerging evidence suggesting neurological consequences, particularly during adolescence, a critical period for brain development. This study examines the memory effects of chronic UPEC UTIs and assesses the therapeutic potential of nitrofurantoin and rosmarinic acid (RA) as adjunctive therapies to antibacterials. In vitro, 65 UPEC isolates from UTI patients were analyzed for antibacterial resistance and biofilm formation using disk diffusion and crystal violet assays, respectively. In vivo, adolescent male Wistar rats were subjected to chronic UPEC infection and treated with nitrofurantoin (30 mg/kg/day), RA (10 mg/kg/day), or their combination. Cognitive function was assessed via the Morris water maze (MWM), a widely used test for spatial learning and memory in rodents, and the novel object recognition test (NORT), a standard test for recognition memory, with hippocampal neuroinflammation (TNF-α, IL-10), oxidative stress (MDA, SOD, CAT, thiol), and cholinergic activity (AChE) quantified. In vitro, 66.2% of UPEC isolates were multidrug-resistant, with biofilm formation strongly correlated with antibiotic resistance (r = 0.72, P < 0.001). In vivo, chronic UPEC infection impaired spatial learning and recognition memory (P < 0.001), increased TNF-α, MDA, and AChE, and reduced IL-10, SOD, CAT, and thiol (P < 0.001). Nitrofurantoin partially alleviated these effects, RA showed greater efficacy, and their combination restored cognitive and biochemical markers to near-control levels (P > 0.05 vs. vehicle). Chronic UPEC UTIs during adolescence induce significant cognitive deficits via neuroinflammation, oxidative stress, and cholinergic dysfunction. The synergistic mitigation of these effects by the combined nitrofurantoin-RA therapy highlights its potential as a novel strategy to address both infection and neurological sequelae. However, further research is crucial to validate these findings across diverse strains and in clinical settings and to explore other potential treatments.