(AAN, BAN, INN, USAN) /mɛtrəˈnaɪdəzoʊl/ (Flagyl and others) is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibacterial against anaerobic organisms, amoebicide and antiprotozoal.[3] It is the drug of choice for first episodes of mild-to-moderate Clostridium difficile infection.[4]
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[5]
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Medical uses
Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along with other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess, gingivitis, amoebiasis, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as Bacteroides fragilis, spp, Fusobacterium spp, Clostridium spp, Peptostreptococcus spp and Prevotella spp.[6] It is also often used to eradicate Helicobacter pylori along with other drugs and to prevent infection in people recovering from surgery.[6]Bacterial vaginosis
Drugs of choice for the treatment of bacterial vaginosis include metronidazole and clindamycin. The treatment of choice for bacterial vaginosis in non-pregnant women include metronidazole oral twice daily for seven days, or metronidazole gel intravaginally once daily for five days, or clindamycin intravaginally at bedtime for seven days. For pregnant women, the treatment of choice is metronidazole oral three times a day for seven days. Data does not report routine treatment of male sexual partners in non-pregnant or pregnant women.[7]Trichomoniasis
The 5-nitroimidazole drugs (metronidazole and tinidazole) are the mainstay of treatment for infection with Trichomonas vaginalis. Treatment for both the infected patient and the patient's sexual partner is recommended, even if asymptomatic. Therapy other than 5-nitroimidazole drugs is also an option, but cure rates are much lower.[8]Clostridium difficile colitis
Initial antibiotic therapy for non-severe Clostridium difficile colitis (pseudomembranous colitis) consists of oral metronidazole or oral vancomycin. Several randomized controlled trials have demonstrated equivalent efficacy of oral metronidazole and oral vancomycin in treating non-severe Clostridium difficile colitis.[9][10][11] However, it has been shown that oral vancomycin is more effective in treating patients with severe Clostridium difficile colitis.[9]Entamoeba histolytica
Invasive colitis and extraintestinal disease including liver abscesses, pleuropulmonary infections, and brain abscesses can result from infection with Entamoeba histolytica. Metronidazole is a widely used drug in patients with invasivs colitis, liver abscesses, pleuropulmonary infection, and/or brain abscesses caused by Entamoeba histolytica.Preterm births
Metronidazole has also been used in women to prevent preterm birth associated with bacterial vaginosis, amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). A randomised controlled trial demonstrated that metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women (selected by history and a positive fFN test) and, conversely, the incidence of preterm delivery was found to be higher in women treated with metronidazole.[12]Adverse effects
Common adverse drug reactions (≥1% of those treated with the drug) associated with systemic metronidazole therapy include: nausea, diarrhoea, weight loss, abdominal pain, vomiting, headache, dizziness and metallic taste in the mouth. Intravenous administration is commonly associated with thrombophlebitis. Infrequent adverse effects include: hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine and paraesthesia.[6] High doses and/or long-term systemic treatment with metronidazole is associated with the development of leucopenia, neutropenia, increased risk of peripheral neuropathy and CNS toxicity.[6]Common adverse drug reaction associated with topical metronidazole therapy include local redness, dryness and skin irritation; and eye watering (if applied near eyes).[6]
Metronidazole may cause mood swings. There is some evidence from studies in rats that supports the possibility of metronidazole may contribute to serotonin syndrome, although no case reports documenting this have been published to date.[13][14]
Mutagenesis and carcinogenesis
Metronidazole is listed by the US National Toxicology Program (NTP) as reasonably anticipated to be a human carcinogen.[15] Although some of the testing methods have been questioned, oral exposure has been shown to cause cancer in experimental animals and has also demonstrated some mutagenic effects in bacterial cultures.[15][16] The relationship between exposure to metronidazole and human cancer is unclear.[15][17] One study (Beard et al. 1988) found an excess in lung cancer among women (even after adjusting for smoking), while other studies (IARC 1987; Thapa et al. 1998) found either no increased risk, or a statistically insignificant risk.[15] [18] Metronidazole is listed as a possible carcinogen according to the WHO International Agency for Research on Cancer (IARC).[19] A study in those with Crohn's disease also found chromosomal abnormalities in circulating lymphocytes in people treated with metronidazole.[16]Due to its potential carcinogenic properties, metronidazole is banned in the European Union and the USA for veterinary use in the feed of animals and is banned for use in any food animals in the USA.[20][21]
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