REVIEW Metronidazole is a nitroimidazole antibiotic medication developed in 1960 used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal.It is the drug of choice for first episodes of mild-to-moderate Clostridium difficile infection.It is marketed in the United States by Pfizer and globally by Sanofi under the trade name Flagyl, and is also sold under other brand names. Metronidazole was developed in 1960. Metronidazole is used also as a gel preparation in the treatment of the dermatological conditions such as rosacea (Rozex and MetroGel by Galderma) and fungating tumours (Anabact, Cambridge Healthcare Supplies). Mechanistically, metronidazole, taken up by diffusion, is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up by anaerobes, it is non-enzymatically reduced by reacting with reduced ferredoxin, which is generated by pyruvate oxido-reductase. Many of the reduced nitroso intermediates will form sulfinamides and thioether linkages with cysteine-bearing enzymes, thereby deactivating these critical enzymes. As many as 150 separate enzymes are affected.In addition or alternatively, the metronidazole metabolites are taken up into bacterial DNA, and form unstable molecules. This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic cells, it has relatively little effect upon human cells or aerobic bacteria.
REFERENCES
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Baines EJ. Metronidazole: its past, present and future. J Antimicrob Chemother. 1978 Sep;4 Suppl C:97-111.
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Brogden RN, Heel RC, Speight TM, Avery GS. Metronidazole in anaerobic infections: a review of its activity, pharmacokinetics and therapeutic use. Drugs. 1978 Nov;16(5):387-417.
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Edwards DI Mechanism of antimicrobial action of metronidazole. J Antimicrob Chemother. 1979 Sep;5(5):499-502.
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Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010 May;31(5):431-55. doi: 10.1086/651706.
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