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Metronidazole: An overview

Author
Melissa Johnson, PharmD
Section Editor
David C Hooper, MD
Deputy Editor
Anna R Thorner, MD

INTRODUCTION

Metronidazole is one of the mainstay drugs for the treatment of anaerobic infections and is the treatment of choice for most patients with mild to moderate Clostridium difficile–associated diarrhea [1,2]. It is approved by the US Food and Drug Administration for the treatment of anaerobic and protozoal infections. Metronidazole exerts its antimicrobial effects through the production of free radicals that are toxic to the microbe.

The use of metronidazole for treating specific infections is discussed separately. (See "Anaerobic bacterial infections" and "Clostridium difficile in adults: Treatment" and "Intestinal Entamoeba histolytica amebiasis" and "Extraintestinal Entamoeba histolytica amebiasis" and "Trichomoniasis".)

MECHANISM OF ACTION

Metronidazole is cytotoxic to facultative anaerobic bacteria such as Helicobacter pylori and Gardnerella vaginalis, but the mechanism of this action is not well understood [3]. However, its activity against obligate anaerobes occurs through a four-step process:

Entry into the microorganism – Metronidazole is a low molecular weight compound that diffuses across the cell membranes of anaerobic and aerobic microorganisms. However, antimicrobial activity is limited to anaerobes [3].

Reductive activation by intracellular transport proteins – Metronidazole is reduced by the pyruvate:ferredoxin oxidoreductase system in obligate anaerobes, which alters its chemical structure. Pyruvate:ferredoxin oxidoreductase normally generates adenosine triphosphate (ATP) via oxidative decarboxylation of pyruvate. With metronidazole in the cellular environment, its nitro group acts as an electron sink, capturing electrons that would usually be transferred to hydrogen ions in this cycle. Reduction of metronidazole creates a concentration gradient that drives uptake of more drug and promotes formation of intermediate compounds and free radicals that are toxic to the cell [3-5].

                         

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Literature review current through: Nov 2016. | This topic last updated: Tue May 31 00:00:00 GMT 2016.
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