Agent-Specific Clinical Profiles of Antibiotic-Associated Encephalopathy: A Dual-Database Pharmacovigilance Study...

Background/Objectives: Antibiotic-associated encephalopathy (AAE) is a serious adverse reaction whose presentation is thought to differ between antibiotics; whether these agent-specific profiles are consistently reflected in spontaneous reports across independent data sources is unknown. Methods: Using the Japanese Adverse Drug Event Report (JADER) database and the US FDA Adverse Event Reporting System (FAERS, 2004-2026), we studied metronidazole, cefepime, ceftriaxone, ceftazidime, and levofloxacin. Encephalopathy was defined by the MedDRA terms Encephalopathy or Toxic encephalopathy, and reporting odds ratios (RORs) were calculated in each database; co-reported neurological manifestations, time to onset, patient age, and renal-associated terms were then characterized. Results: All five antibiotics showed significant reporting disproportionality in both databases, with metronidazole and cefepime showing the largest RORs in each (JADER: metronidazole ROR 186.70, cefepime 55.33; FAERS: cefepime 69.29, metronidazole 29.11), consistent with established adverse reactions. In FAERS, metronidazole showed a cerebellar profile (ataxia OR 12.48, dysarthria OR 11.11) and cefepime a renal-associated altered-mental-status/myoclonus profile (depressed level of consciousness OR 12.88, myoclonus OR 11.76; renal-associated terms OR 2.88; median age 71 years); event-specific JADER dates indicated a delayed course for metronidazole (median 28 days). The symptom-level contrast was FAERS-based and was not reproduced when the same analysis was repeated in JADER, a discrepancy that may reflect differences in coding practice. Conclusions: AAE is reported not as a single uniform event but with profiles specific to the causative antibiotic. Awareness of these agent-specific patterns may support earlier recognition, although confirmation in analytic studies with exposure denominators is warranted.