ANTIMICROBIAL: Metronidazole

CLASS: Nitroimidazole

SOME OTHER ANTIMICROBIALS IN THE SAME CLASS: Tinidazole

ORIGINS: In the mid-1950s at Rhone-Poulenc labs, extracts of Streptomyces spp. were discovered to have activity against Trichomonas vaginalis. Metronidazole, a synthetic derivative of one of these compounds, was used to treat chronic trichomonad infections, beginning in 1959. It was not until 1962 that it was discovered to have activity against anaerobic bacteria when shown to help treat gingivitis.

MECHANISM OF ACTION: Metronidazole is a pro-drug. Metronidazole is selective for anaerobic bacteria due to these bacteria being able to reduce metronidazole to its active form inside the cell. The metronidazole then covalently binds to DNA, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death.

MAIN CLINICAL USES: Parasitic infections such as those caused by Entamoeba histolytica, Giardia lamblia, and Trichomonas vaginalis. Clinical conditions where anaerobic bacteria are significantly involved, such as gingivitis, intra-abdominal infections, gynaecological infections. Metronidazole is also used in combination with other drugs for Helicobacter pylori eradication, and for the treatment of Clostridium difficile associated disease.

ROUTE OF ADMINISTRATION: Oral, IV and topical. (It achieves good systemic levels when taken orally. Occasionally used topically for treatment of rosacea and also bacterial vaginosis.

MAIN SIDE EFFECTS OF NOTE: GI and taste disturbance are the most common. Hepatitis relatively rare.

RESISTANCE: Still relatively rare. Has been described in Bacteroides species, Clostridium difficile and Helicobacter pylori. Mechanism is unclear but may be a combination of decreased uptake and decreased nitro-reductase activity.

OTHER POINTS OF NOTE: Consuming alcohol whilst taking metronidazole can cause a disufiram type reaction (antabuse effect).Metronidazole has also been shown to have carcinogenic potential, so prolonged or unnecessary use is avoided.