Metronidazole (Flagyl)

Metronidazole in Brief
  • Generic name : Metronidazole
  • Brand names: Flagyl
  • Therapeutic class: Antibiotic; Antiprotozoal; Anaerobic antibacterial;
  • Pharmacologic class: Nitroimidazole
  • Chemical Formula: C6H9N3O3
  • Pregnancy Category: B (however, it is recommended to avoid metronidazole use during the first trimester)
  • Originally discovered: 1950s, France France

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch


Metronidazole is an antiprotozoal and antibacterial medication used mainly in the treatment of 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 member 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 as antiparasitic 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.

Currently, metronidazole 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 in combination with other agents is widely used 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 often used for Crohn's disease, a chronic inflammatory disease of the digestive system. 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. It is used to treat active disease and may help with symptoms when aminosalicylates do not work; keep symptoms of Crohn's disease from coming back after surgery.

Giardiasis is an intestinal infection caused by a parasitic microscopic parasite Giardia lamblia. Metronidazole is an effective antimicrobial agent for treatment of giardiasis. It provides a a cure rate of about 85-90% 6. Metronidazole dosage regimen for the treatment of giardiasis is 250 mg 3 times a day for 5-7 days.

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. According to the Infectious Diseases Society of America guidelines11 metronidazole is the first-line therapy for the initial episode of mild-to-moderate disease. The recommendation is based on metronidazole's high in vivo activity against C. difficile, its low cost as well as a growing concern of emerging resistance to other important antibiotics 9.

See also metronidazole vs vancomycin for 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 (active at low pH). 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.

Ulcerative gingivitis. Metronidazole (alone or in combination with other antibacterials) provides an effective therapy for gum disease 10.

Guinea worms
Metronidazole may facilitate removal of adult guinea worms in dracunculiasis.


Metronidazole "pros" and "cons"


  • Variety of available formulations -- oral, intravenous, intravaginal, and topical.
  • Oral metronidazole is extremely well absorbed.
  • Bactericidal activity against obligate anaerobes.
  • Excellent activity against anaerobic gram-negative bacilli, including B. fragilis that are frequently resistant to other antibiotics 8.
  • Excellent penetration into almost all body tissue and fluids, including saliva, vaginal seminal fluids, and cerebrospinal fluid.
  • Minimal suppression of normal gut flora. Does not induce antibiotic-associated diarrhea (pseudomembranous colitis).
  • Metronidazole can promote wound healing and epithelization process 8.
  • Very low cost.
  • Relatively mild side effects.


  • 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.
  • Frequently causes unpleasant, metallic taste in the mouth.
  • Metronidazole is active only against anaerobes and cannot used as a monotherapy in mixed infections.
  • Undergoes extensive hepatic metabolism.
  • Metronidazole may potentiate the anticoagulant effect of warfarin and other coumarin anticoagulants.
  • Sensory neuropathies12 (numbness, paresthesias) have been reported. The reversal of severe neuropathies may be slow or incomplete.

Mode of action

Metronidazole is bactericidal. The drug affects DNA replication by inhibiting nucleic acid synthesis. 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
  • 8. Treviño M, Areses P, Peñalver MD, Cortizo S, Pardo F, del Molino ML, García-Riestra C, Hernández M, Llovo J, Regueiro BJ. Susceptibility trends of Bacteroides fragilis group and characterisation of carbapenemase-producing strains by automated REP-PCR and MALDI TOF. Anaerobe. 2012 Feb;18(1):37-43. PubMed
  • 9. Seltman AK. Surgical Management of Clostridium difficile Colitis. Clin Colon Rectal Surg. 2012 Dec;25(4):204-9.
  • 10. Pradeep AR, Kumari M, Priyanka N, Naik SB. Efficacy of chlorhexidine, metronidazole and combination gel in the treatment of gingivitis--a randomized clinical trial. J Int Acad Periodontol. 2012 Oct;14(4):91-6. PubMed
  • 11. Clinical practice guidelines for Clostridium difficile infection IDSA 2017 Update PDF Infectious Diseases Society of America
  • 12. Zivkovic SA1, Lacomis D, Giuliani MJ. Sensory neuropathy associated with metronidazole: report of four cases and review of the literature. J Clin Neuromuscul Dis. 2001 Sep;3(1):8-12.
  • 13. Trindade LC, Biondo-Simões Mde L, Sampaio CP, Farias RE, Pierin RJ, Netto MC. Evaluation of topical metronidazole in the healing wounds process: an experimental study. Rev Col Bras Cir. 2010 Oct;37(5):358-63. PubMed
  • 14. Mallikarjuna Rao C, Ghosh A, Raghothama C, Bairy KL. Does metronidazole reduce lipid peroxidation in burn injuries to promote healing? Burns. 2002 Aug;28(5):427-9. PubMed

Published: March 31, 2008
Last updated: January 28, 2017

Interesting facts

Metronidazole facts
  • Many health care professionals still consider metronidazole to be the 'gold standard' antibiotic against which all other anti-anaerobic agents should be compared.
  • Metronidazole is a prodrug, and requires reductive activation of the nitro group by susceptible organisms to become active. So, metronidazole is not pharmacologically active itself.

More Facts
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