Clinical question: What is the prevalence of metronidazole-related neurologic adverse events and what are the risk factors associated with these events?
Background: A 2021 study reported neurologic events occurring in 0.25% of patients aged 65 or older who received metronidazole. Effects associated with metronidazole include polyneuropathy, dysarthria, ataxia, and encephalopathy. A prior review reported that peripheral neuropathy was more common in patients receiving metronidazole for more than four weeks or total doses over 42 g. Little is known about other risk factors.
Study design: Case-control study
Setting: 2,400-bed tertiary care hospital in South Korea
Synopsis: Case patients were those diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy. Control patients were those prescribed metronidazole who did not develop neurologic adverse events.
Between January 2006 and July 2021, 61,158 patients were treated with metronidazole for at least five days. Of these, 54 patients (0.09%) developed metronidazole-associated encephalopathy or peripheral neuropathy. These patients were significantly older and received metronidazole for a significantly longer duration (51 days) compared to those who did not develop neurologic adverse events (10 days).
After matching for age, duration of therapy, and cumulative dose, the authors conducted conditional logistic regression analysis. Liver cirrhosis, chronic kidney disease (CKD), IV administration, and lower body weight were associated with metronidazole-associated neurologic adverse events in the multivariable analysis.
The incidence of metronidazole-associated neurologic adverse events was lower in this study (0.09%) than in a prior study of older patients (0.25%), possibly due to stricter diagnostic criteria or a younger patient population. Limitations of the study included its being conducted at a single center. As this was a case-control study, there was a risk of assessor bias and confounding.
Bottom line: IV administration, liver cirrhosis, CKD, and lower body weight were associated with metronidazole-associated encephalopathy or peripheral neuropathy. The overall incidence of neurologic events was low.
Citation: Lee SJ, et al. Frequency and risk factor analysis for metronidazole-associated neurologic adverse events. J Gen Intern Med. 2024;39(6):912-20.
Dr. Kerwin
Dr. Kerwin is a hospitalist in the division of hospital medicine at the Mount Sinai Health System and an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.