Association Between First-time Neurologic Events and Metronidazole Treatment: A Case-time Control Study

• Published in: Clinical therapeutics 2024-04, Vol.46 (4), p.307-312
• Main Authors: Andersen, Michael Asger, Gregersen, Rasmus, Petersen, Tonny Studsgaard, Wang, Joanna Nan, Petersen, Janne, Jimenez-Solem, Espen
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adverse drug reaction; Aged; Aged, 80 and over; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; Brain Diseases - chemically induced; Brain Diseases - epidemiology; Case reports; Case-Control Studies; Cerebellar Diseases - chemically induced; Cerebellar Diseases - epidemiology; Cerebellar dysfunction; Cerebellum; Denmark - epidemiology; Diabetes; Drug dosages; Encephalitis; Encephalopathy; Female; Humans; Incidence; Male; Metronidazole; Metronidazole - administration & dosage; Metronidazole - adverse effects; Middle Aged; Patients; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - epidemiology; Peripheral neuropathy; Registries; Side effects; Statistical analysis; Subgroups; Windows (intervals)
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2024.02.003

•Metronidazole induced neurologic events linked through nationwide registries.•0.16% 100-day incidence rates for peripheral neuropathy.•0.02% 100-day incidence rates for cerebellar dysfunction.•No significant association with neurologic events.•Continued clinical vigilance despite low event incidence. Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59–1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use. [Display omitted]