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Int J Antimicrob Agents. 2018 Mar;51(3):319-325. doi: 10.1016/j.ijantimicag.2017.08.033. Epub 2017 Sep 5.

Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

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Department of Pharmacy, Atlanta Veteran Affairs Medical Center (AVAMC), 1670 Clairmont Rd, Decatur, GA 30033, USA. Electronic address:
Department of Pharmacy Practice and Administrative Sciences, University of New Mexico College of Pharmacy, 1 University of New Mexico, MSC 09 5360, Albuquerque, NM 87131, USA.
Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA; Department of Medicine, Atlanta Veteran Affairs Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA.


The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated, but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy, with most cases (31/40) receiving a >42 g total (>4 weeks) of therapy. In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0 to 50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 g total (>4 weeks) of metronidazole compared with those patients receiving ≤42 g total (17.9% vs. 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is rare in patients who receive ≤42 g total of metronidazole. Patients who receive higher total doses may be at higher risk of peripheral neuropathy, but symptoms resolve after discontinuation of therapy in most patients. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 g total of the drug (≤4 weeks).


Antimicrobial stewardship; Metronidazole; Peripheral neuropathy

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