Metronidazole

Metronidazole (INN) (IPA: ) is a nitroimidazole anti-infective drug used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. It is marketed by Pfizer under the trade name Flagyl, and also by various generic manufacturers, who sell it at a cheaper price. Metronidazole is also used in the treatment of the dermatological condition rosacea, where it is marketed by Galderma under the trade names Rozex and MetroGel.

Metronidazole is a prodrug. It is converted in anaerobic organisms by the redox enzyme pyruvate-ferredoxin oxidoreductase. The nitro group of metronidazole is chemically reduced by ferredoxin (or a ferredoxin-linked metabolic process) and the products are responsible for disrupting the DNA helical structure, thus inhibiting nucleic acid synthesis.

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.

Indications
Systemic metronidazole is indicated for the treatment of:
 * Vaginitis due to Trichomonas vaginalis (protozoal) infection in both symptomatic patients as well as their asymptomatic sexual contacts; and due to bacterial Gardnerella or Mycoplasma hominis infection in symptomatic patients
 * Pelvic inflammatory disease in conjunction with other antibiotics such as ofloxacin, levofloxacin, or ceftriaxone
 * Protozoal infections due to Entamoeba histolytica (Amoebic dysentery or Hepatic abscesses), and Giardia lamblia (Giardiasis) should be treated alone or in conjunction with iodoquinol or diloxanide furoate
 * Anaerobic bacterial infections such as Bacteroides fragilis, spp, Fusobacterium spp, Clostridium spp, Peptostreptococcus spp, Prevotella spp, or any other anaerobes in intraabdominal abscess, peritonitis, empyema, pneumonia, aspiration pneumonia, lung abscess, diabetic foot ulcer, meningitis and brain abscess, bone and joint infections, septicemia, endometritis, tubo-ovarian abscess, or endocarditis
 * Pseudomembranous colitis due to Clostridium difficile
 * Helicobacter pylori eradication therapy, as part of a multi-drug regimen in peptic ulcer disease
 * Prophylaxis for those undergoing potentially contaminated colorectal surgery and may be combined with neomycin
 * Acute gingivitis and other dental infections (TGA approved, non-Food and Drug Administration (FDA) approved)
 * Crohn's disease with colonic or perianal involvement (non-FDA approved)

Topical metronidazole is indicated for the treatment of rosacea, and has been used in the treatment of malodorous fungating wounds.

Prevention of 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 and, conversely, the incidence of preterm delivery was actually higher in women treated with metronidazole.

Lamont has argued that Metronidazole is not the right antibiotic to administer in these circumstances and was often administered too late to be of use. Clindamycin administered early in the second trimester to women who test positive for bacterial vaginosis seems to be more effective.

Adverse effects
Common adverse drug reactions (≥1% of patients) associated with systemic metronidazole therapy include: nausea, diarrhea, and/or 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/or paraesthesia.

High doses and/or long-term systemic treatment with metronidazole is associated with the development of black hairy tongue, leukopenia, neutropenia, increased risk of peripheral neuropathy and/or CNS toxicity.

Metronidazole is listed by the International Agency for Research on Cancer (IARC) as a potential human carcinogen. Although some of the testing methods have been questioned, it has been shown to cause cancer in experimental animals. Nevertheless, it appears to have a fairly low potential for cancer risk and under most circumstances the benefits of treatment outweighs the risk.

Common adverse drug reactions associated with topical metronidazole therapy include local redness, dryness, and/or skin irritation; and eye watering (if applied near eyes).

Interaction with alcohol
Co-administration of metronidazole and ethanol (alcohol) results, rarely, in a disulfiram-like reaction (nausea, vomiting, flushing, tachycardia). Consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 24 hours after completion of treatment. However, the occurrence of this reaction in the clinical setting has recently been questioned by some authors.