Antibiotic-associated encephalopathy: A retrospective pharmacovigilance study based on 21 years of data from the US FDA Adverse Event Reporting System

Antibiotic-associated encephalopathy (AAE) is a serious adverse drug reaction that can cause significant neurological complications. This study aimed to identify the antibiotics associated with AAE by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), thereby providing insights into antibiotic-related neurotoxicity risks. Disproportionality analysis was performed using the reporting odds ratio method based on FAERS data from Q1 2004 to Q4 2024. A total of 87 preferred terms potentially related to AAE were identified. Antibiotics classified under Anatomical Therapeutic Chemical codes J01 to J07 and other antimicrobial agents were included. All identified antibiotics were grouped into 3 categories according to their clinical neurotoxic profiles. In total, 13,698 patients with AAE were identified over the 21-year period. The 5 most frequently reported antibiotics were metronidazole (1464 cases), levofloxacin (1447), ciprofloxacin (1290), ertapenem (825), and imipenem/cilastatin (788). The incidence of AAE increased with age. Among the 121 antibiotics analyzed, 52 showed positive reporting odds ratio signals: 28 were classified as type 1, 6 as type 2, and 18 as type 3. Most AAE cases occurred within 10 days of antibiotic exposure, except for several agents, including meropenem/vaborbactam and ticarcillin/clavulanic acid (type 1), and isoniazid, pyrazinamide, rifampicin, and paromomycin (type 3), which exhibited delayed onset. This study represents the first large-scale pharmacovigilance analysis of AAE using FAERS data and identifies 52 antibiotics with significant neurotoxicity signals. Most antibiotics trigger early-onset AAE, and older patients demonstrate greater susceptibility. These findings expand our understanding of AAE and inform safer antibiotic use.