TY - JOUR

T1 - Association Between First-Time Neurologic Events and Metronidazole Treatment

T2 - A Case-Time Control Study

AU - Andersen, Michael Asger

AU - Gregersen, Rasmus

AU - Petersen, Tonny Studsgaard

AU - Wang, Joanna Nan

AU - Petersen, Janne

AU - Jimenez-Solem, Espen

N1 - Publisher Copyright: © 2024 The Author(s)

PY - 2024

Y1 - 2024

N2 - Purpose: 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. Methods: 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. Findings: 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. Implications: 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.

AB - Purpose: 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. Methods: 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. Findings: 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. Implications: 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.

KW - Adverse drug reaction

KW - Cerebellar dysfunction

KW - Encephalitis

KW - Metronidazole

KW - Peripheral neuropathy

U2 - 10.1016/j.clinthera.2024.02.003

DO - 10.1016/j.clinthera.2024.02.003

M3 - Journal article

C2 - 38493002

AN - SCOPUS:85187986940

JO - Clinical Therapeutics

JF - Clinical Therapeutics

SN - 0149-2918

ER -