Neurotoxicity of Broad-Spectrum Antibiotics in Urinary Tract Infections: Mechanisms and Clinical Implications

Urinary tract infections (UTIs) remain among the most common bacterial infections worldwide, affecting millions every year. While Escherichia coli (E. coli) is the predominant pathogen, a broad range of Gram-negative and Gram-positive organisms can be implicated. Treating UTIs, particularly complicated or severe infections, frequently relies on broad-spectrum antibiotics, often started empirically before identifying the causative pathogen. However, despite their ability to cover a wide spectrum of pathogens, they have become a growing threat to public health, mainly due to the rise of antimicrobial resistance, but also due to the many other adverse effects they can potentially cause. Neurotoxicity represents one of the most consequential yet underrecognized complications of antibiotic therapy. Broad-spectrum agents commonly used for UTIs, including fosfomycin, fluoroquinolones, carbapenems, and cephalosporins, have been associated with a wide range of neurologic manifestations such as epileptic seizures, encephalopathy, movement disorders, delirium, and psychosis, varying in onset, duration, severity, and reversibility. To induce such reactions, antibiotics interact with the central nervous system (CNS) in several ways that can threaten its integrity and disrupt homeostatic control of its components. This review provides a synopsis of the known neurological adverse reactions linked to four major antibiotic classes routinely used in UTI management and the mechanistic pathways underlying CNS toxicity. An overall clearer understanding of these risks may help clinicians balance therapeutic benefit against potential harm, optimize antimicrobial selection, and improve prevention and management strategies for antibiotic-associated neurotoxicity.