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Metronidazole (Flagyl)

Metronidazole in Brief
  • Active ingredient: Metronidazole
  • Brand names: Flagyl
  • Drug class: Antibiotic; Antiprotozoal; Anaerobic antibacterial; Nitroimidazole
  • Chemical Formula: C6H9N3O3
  • Pregnancy Category: B
  • Originally discovered: 1950s, France France

Metronidazole is an antiprotozoal and antibacterial medication used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria (organism which does not require oxygen for growth) and protozoa. It is marketed by Pfizer under the trade name Flagyl in the US, while Sanofi-Aventis markets metronidazole globally under the same trade name, Flagyl, and also by various generic manufacturers.


Metronidazole was synthesized by France's Rhone-Poulenc laboratories and introduced in the mid-1950s under the brand name Flagyl. It was the first of the group of drugs that are now called nitroimidazoles. In the US it was licensed to Searle.

Metronidazole is one of the rare examples of a drug developed against a parasite which has since gained broad use as an antibacterial agent. Briefly, at Rhone-Poulenc labs, extracts of Streptomyces spp. were screened for activity against Trichomonas vaginalis, a cause of vaginal itching. Azomycin, a nitroimidazole, was identified, and metronidazole, a synthetic derivative, was used to treat chronic trichomonad infections, beginning in 1959.

The antibacterial activity of metronidazole was discovered by accident in 1962 when metronidazole cured a patient of both trichomonad vaginitis and bacterial gingivitis. However, it was not until the 1970s that metronidazole was popularized for treatment of infections caused by gram-negative anaerobes such as bacteroides or gram-positive anaerobes such as clostridia.

Presently, metronidazole, which is inexpensive, has good tissue penetration, and produces relatively mild side effects, is on the formulary at most hospitals for prophylaxis against anaerobic infection after bowel surgery, for treatment of wound abscess, and for treatment of antibiotic-associated colitis caused by Clostridium difficile. Metronidazole is an important part of combination therapy against Helicobacter pylori, a major cause of gastritis and a risk factor for stomach cancer.

FDA approved uses

The nitroimidazole antibiotic metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment.

Metronidazole is indicated for the treatment of the following infections due to susceptible strains of sensitive organisms:

  • Trichomoniasis: symptomatic, asymptomatic, asymptomatic consorts
  • Amebiasis: acute intestinal amebiasis (amebic dysentery) and amebic liver abscess
  • Anaerobic Bacterial Infections
  • Intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess
  • Skin and skin structure infections
  • Gynecologic infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection
  • Bacterial Septicemia
  • Bone and joint infections, as adjunctive therapy
  • Central Nervous System infections, including meningitis and brain abscess
  • Lower Respiratory Tract infections, including pneumonia, empyema, and lung abscess
  • Endocarditis

Metronidazole is NOT effective for infections caused by aerobic bacteria that can survive in the presence of oxygen. Metronidazole is only effective against anaerobic bacterial infections because the presence of oxygen will inhibit the nitrogen-reduction process that is crucial to the drug's mechanism of action.

Off-label & Investigational uses

Crohn's disease
Metronidazole3-4 is one of the most commonly used antibiotic for Crohn's disease. Metronidazole may be used to treat infections that develop because of Crohn's disease, especially when abscesses, abnormal connections (fistulas) between two parts of the intestines; treat active disease and may help with symptoms when aminosalicylates do not; keep symptoms of Crohn's disease from coming back after surgery.

Giardiasis is an intestinal infection caused by a parasitic organism called Giardia lamblia. Metronidazole is the antimicrobial agent most commonly used in the treatment of giardiasis in the United States. It has a cure rate of 85-90% 6.

Clostridium Difficile Colitis
Antibiotics are known to disrupt the colonic microflora, facilitating C. difficile colonization and growth. C difficile, a spore-forming gram-positive rod, produces toxins that inflame the colon. Rarely, the toxins destroy the tissue of the inner lining of the colon.

Virtually any antibiotic may induce C. difficile colitis, but broad-spectrum antibiotics with activity against enteric bacteria are the most frequent culprits. Metronidazole is the first-line therapy for reasons of cost as well as concern about resistance. It has high in vivo activity against C difficile.

Helicobacter pylori infections
Infection with Helicobacter pylori can cause chronic gastritis and lead to peptic ulcer disease. The infection is usually acquired during childhood and, if eradicated, is believed to rarely recur during adult life. The two main antibiotics used are metronidazole and clarithromycin. Metronidazole is active against H. pylori 7, and its bioavailability is not influenced by acid suppression. However, H.pylori easily becomes resistant to metronidazole.

Hepatic encephalopathy
Hepatic encephalopathy is a brain disorder due to liver failure. It occurs when toxins such as ammonia and mercaptans accumulate in the blood and reach the brain. Metronidazole 5 works by decreasing intestinal ammonia production by colon bacteria.

Metronidazole "pros" and "cons"


  • Favorable pharmacokinetic and pharmacodynamic properties.
  • Excellent penetration into almost all body tissue and fluids
  • Minimal suppression of normal gut flora. Does not induce antibiotic-associated diarrhea (pseudomembranous colitis).
  • Bactericidal activity.


  • Carcinogenic potential. Metronidazole hydroxy metabolite is potentially a carcinogen1. Also, metronidazole is a proven carcinogenic to animals. It has shown to have tumorigenic activity in mice and rats, the most prominent being pulmonary lesions in the mouse. Unnecessary use of metronidazole should be avoided.
  • Mutagenicity. Metronidazole is mutagenic in rodents and bacteria. However, teratogenicity in humans has not been demonstrated.
  • Alcohol interaction.
    Consuming alcohol while taking metronidazole causes a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia (accelerated heart rate), shortness of breath, and even death. Consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 24 hours after completion of treatment. However, the mechanism of this reaction has recently been questioned by some researches, and a possible central toxic reaction for the alcohol intolerance suggested.
  • Gastrointestinal tract and nervous system toxicity. Acute toxicity causes gastrointestinal tract symptoms. Chronic toxicity causes neurological damage. There is the risk of convulsive seizures and peripheral neuropathy with long-term use.
Mode of action

Metronidazole is bactericidal. The activity of metronidazole against Trichomonas, amoebae and Giardia is also likely to be attributable to disruption of existing DNA and inhibition of its synthesis in those organisms.

Metronidazole is selectively taken up by anaerobic bacteria and sensitive protozoal organisms because of the ability of these organisms to reduce metronidazole to its active form intracellularly.

Time to clear out of the system

The half-life of Metronidazole is about 8 hours. So it takes about 1-2 days to clear out of the system.

Further reading
  • 1. Menendez D, Bendesky A, Rojas E, Salamanca F, Ostrosky-Wegman P. Role of P53 functionality in the genotoxicity of metronidazole and its hydroxy metabolite. Mutat Res. 2002 Apr 25;501(1-2):57-67.
  • 2. Wenisch C, Parschalk B, Hasenhundl M, Hirschl AM, Graninger W. Treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996 May;22(5):813-8. PubMed
  • 3. Prantera C, Zannoni F, Scribano ML, Berto E, Andreoli A, Kohn A, Luzi C. An antibiotic regimen for the treatment of active Crohn's disease. Am J Gastroenterol. 1996 Feb;91(2):328-32.
  • 4. Froehlich F, Juillerat P, Felley C, Mottet C, Vader JP, Burnand B, Michetti P, Gonvers JJ. Treatment of postoperative Crohn's disease. Digestion. 2005;71(1):49-53.
  • 5. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982 Jan;23(1):1-7. PubMed
  • 6. Gardner T, Hill D. Treatment of giardiasis. Clin Microbiol Rev. 2001 Jan;14(1):114-28.
  • 7. Murakami K, Okimoto T, Kodama M, Sato R, Watanabe K, Fujioka T. J Clin Gastroenterol. 2008 Feb;42(2):139-42. PubMed

Published: March 31, 2008
Last updated: December 17, 2013

Interesting facts

Metronidazole facts
  • Many health care professionals still consider metronidazole to be the 'gold standard' antibiotic against which all other antibiotics with anaerobic activity should be compared.