Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis. It is an option for a first episode of mild-to-moderate Clostridioides difficile colitis if vancomycin or fidaxomicin is unavailable. Metronidazole is available orally (by mouth), as a cream or gel, and by slow intravenous infusion (injection into a vein). Common side effects include nausea, a metallic taste, loss of appetite, and headaches. Occasionally seizures or allergies to the medication may occur. Metronidazole began to be commercially used in 1960 in France. It is on the World Health Organization's List of Essential Medicines. It is available in most areas of the world. In 2023, it was the 203rd most commonly prescribed medication in the United States, with more than 2 million prescriptions.
Medical uses
Metronidazole has activity against some protozoans and most anaerobic bacteria (both gram-negative and gram-positive classes) but not the aerobic bacteria. 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, periodontal disease, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus, and Prevotella species. It is also often used along with other drugs to eradicate Helicobacter pylori and to prevent infection in people recovering from surgery. Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. This may require hydrolysis in the gastrointestinal tract and some sources speculate that it may be unsuitable in people with diarrhea or feeding-tubes in the duodenum or jejunum.
Bacterial vaginosis Drugs of choice for the treatment of bacterial vaginosis include metronidazole and clindamycin. An effective treatment option for mixed infectious vaginitis is a combination of clotrimazole and metronidazole.
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.
Giardiasis Oral metronidazole is a treatment option for giardiasis. However, the increasing incidence of nitroimidazole resistance is leading to the increased use of other compound classes.
Dracunculus In the case of Dracunculus medinensis (Guinea worm), metronidazole merely facilitates worm extraction rather than killing the worm.
C. difficile colitis Initial antibiotic therapy for less-severe Clostridioides difficile infection colitis (pseudomembranous colitis) consists of metronidazole, vancomycin, or fidaxomicin by mouth. In 2017, the IDSA generally recommended vancomycin and fidaxomicin over metronidazole. Vancomycin by mouth has been shown to be more effective in treating people with severe C. difficile colitis.
E. histolytica Entamoeba histolytica invasive amebiasis is treated with metronidazole for eradication, in combination with diloxanide to prevent recurrence. Although it is generally a standard treatment it is associated with some side effects.
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). 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.
Hypoxic radiosensitizer In addition to its anti-biotic properties, attempts were also made to use a possible radiation-sensitizing effect of metronidazole in the context of radiation therapy against hypoxic tumors. However, the neurotoxic side effects occurring at the required dosages have prevented the widespread use of metronidazole as an adjuvant agent in radiation therapy. However, other nitroimidazoles derived from metronidazole such as nimorazole with reduced electron affinity showed less serious neuronal side effects and have found their way into radio-onological practice for head and neck tumors in some countries.
Perioral dermatitis Metronidazole gel or cream is used as a first line treatment for perioral dermatitis for its anti-inflammatory effects. Canadian Family Physician has recommended topical metronidazole as a third-line treatment for the perioral dermatitis either along with or without oral tetracycline or oral erythromycin as first and second line treatment respectively.
Adverse effects Common adverse drug reactions (≥1% of those treated with the drug) associated with systemic metronidazole therapy include: nausea, diarrhea, 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. High doses and long-term systemic treatment with metronidazole are associated with the development of leucopenia, neutropenia, increased risk of peripheral neuropathy, and central nervous system toxicity. Common adverse drug reaction associated with topical metronidazole therapy include local redness, dryness and skin irritation; and eye watering (if applied near eyes). Metronidazole has been associated with carcinogenic activity in animal studies. In rare cases, it can also cause temporary hearing loss that reverses after cessation of the treatment. Some evidence from studies in rats indicates the possibility it may contribute to serotonin syndrome, although no case reports documenting this have been published to date.
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