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Medicines update
What do I need to know about metronidazole?
  1. Geoffrey Burnhill,
  2. Elizabeth Starkey
  1. Department of Paediatrics, Derbyshire Children’s Hospital, Derby, UK
  1. Correspondence to Dr Elizabeth Starkey, Derbyshire Children’s Hospital, Derby, DE22 3NE, UK; elizabeth.starkey{at}nhs.net

https://doi.org/10.1136/archdischild-2017-313589

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    Introduction

    Although it has been in use for over 50 years, metronidazole continues to be widely prescribed for the treatment of anaerobic bacterial infections as well as in some protozoal diseases. Despite this long-term use, relatively little resistance has emerged and metronidazole remains the treatment of choice for Helicobacter pylori infection, bacterial vaginosis and Clostridium difficile colonisation as well as suspected deep anaerobic infections in both adults and children.1

    Mode of action

    Metronidazole is bactericidal and targets organisms that thrive in anaerobic conditions. The mechanism behind this action is multifactorial and revolves around the ability of the nitroimidazole ring within metronidazole to undergo reduction. Reduction of this ring inherently causes disruption of the normal redox energy pathways of the bacterium and produces a reactive nitro radical anion. This reactive anion goes on to cause oxidative damage to microbial DNA, which cannot then be repaired due to deficiency of available energy stores. Presence of oxygen prevents this action as it can readily accept lone electrons from the reactive drug radical, explaining the effect of the drug only in anaerobic environments.2

    This mode of action is independent of binding to microbial proteins and the drug passively diffuses across the microbial membrane. As a result, organisms are not able to quickly develop resistance by modification of protein structure, possibly explaining the relative lack of resistance to the drug today.

    Pharmacokinetics

    Absorption

    Metronidazole is absorbed well orally and has a bioavailability of 98.9% when taken by this route. Mean peak plasma concentrations of metronidazole (10.49±3.44 µg/mL) are reached within approximately 6 hours (4.48±1.7 hours) of ingestion in children.3

    Intravenous administration is commonly used in those who are nil by mouth, for example those pre and post gastrointestinal surgery or neonates …

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    Footnotes

    • Contributors GB has written the article with amendments and reviews undertaken by ES.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; internally peer reviewed.