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Metronidazole-Induced Central Nervous System Toxicity: A Systematic Review

Kuriyama, Akira MD*; Jackson, Jeffrey L. MD, MPH; Doi, Asako MD; Kamiya, Toru MD§

doi: 10.1097/WNF.0b013e3182334b35
Original Articles

Objective To assess patient and medication factors that contribute to metronidazole toxicity.

Data Sources We searched PUBMED from 1965 through April 7, 2011, and performed a hand search of bibliographies.

Study Selection Case reports or case series reporting metronidazole-induced central nervous toxicity.

Data Extraction Two authors independently abstracted demographics, metronidazole indication, dose and duration, neurological manifestations, and outcomes as well as brain imaging findings.

Data Synthesis Among 64 patients, 48 (77%) had cerebellar dysfunction, 21 (33%) had altered mental status, and 8 (15%) had seizures. Patients’ ages averaged 53.3 years (range, 12–87 years), and 64% were male. The median duration of metronidazole was 54 days, although 26% had taken it less than a week and 11% had taken it less than 72 hours. Among cases with outcome data, most patients either improved (n = 18 [29%]) or had complete resolution of their symptoms with discontinuation of metronidazole (n = 41 [65%]). There was no difference in resolution of symptom by age (P = 0.71) or sex (P = 0.34). The patients with cerebellar dysfunction were less likely to experience complete resolution than those with mental status changes or seizures (relative risk, 0.67; 95% confidence interval (CI), 0.49–0.92). Nearly all patients (n = 55 [86%]) underwent imaging of the brain: 44 (69%) underwent magnetic resonance imaging (MRI) and 12 (19%) underwent computed tomographic studies. All patients with cerebellar dysfunction had abnormalities on imaging: 93% (n = 39) had a cerebellar lesion, although numerous areas in the brain were affected. On follow-up MRIs, 25 patients (83%) had complete resolution of abnormalities.

Conclusions Metronidazole can rarely cause central nervous system toxicity; it does not seem to be a dose- or duration-related phenomenon. Most patients will have MRI abnormalities. Prognosis is excellent with metronidazole cessation.

*Department of General Internal Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan; †GIM Section, Medical College of Wisconsin, Milwaukee, WI; ‡Department of Infectious Diseases, Rakuwakai Otowa Hospital, Kyoto, Japan; and §Department of Infectious Diseases and Department of General Internal Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan.

Disclaimer: The viewpoints reflected in this manuscript are those of the authors and should be not be construed to reflect, in any way, those of the US Government or the Department of Veteran Affairs. Drs Jackson and Kuriyama had full access to the data and take full responsibility for the integrity of the data and analysis of the same.

Conflicts of Interest and Source of Funding: There was no funding for this project. The authors have no conflicts of interest to declare.

Address correspondence and reprint requests to Jeffrey L. Jackson, MD, MPH, 5100 W National St, Milwaukee, WI 53215; E-mail: jjackson@mcw.edu

© 2011 Lippincott Williams & Wilkins, Inc.