Metronidazole is a nitroimidazole antiprotozoal drug (potent antibacterial activity against anaerobes, including Bacteroides and Clostridium species. Metronidazole is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up by anaerobes, it is nonenzymatically reduced by reacting with reduced ferredoxin. This reduction results in prod-ucts that are toxic to anaerobic cells, and allows for their selective accumulation in anaerobes. The metabolites of metronidazole are taken up into bacterial DNA, forming unstable molecules. This action only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic cells, it has relatively little effect on human cells or aerobic bacteria.
Metronidazole is well absorbed after oral administration, is widely distributed in tissues, and reaches serum levels of 4–6 mcg/mL after a 250-mg oral dose. It can also be given intravenously or by rectal suppository. The drug penetrates well into the cerebrospinal fluid and brain, reaching levels similar to those in serum. Metronidazole is metabolized in the liver and may accumulate in hepatic insuf-ficiency.
Metronidazole is indicated for treatment of anaerobic or mixed intra-abdominal infections (in combination with other agents with activity against aerobic organisms), vaginitis (trichomonas infection, bacterial vaginosis), Clostridium difficile colitis, and brain abscess. The typical dosage is 500 mg three times daily orally or intravenously (30 mg/kg/d). Vaginitis may respond to a single 2 g dose. A vaginal gel is available for topical use.
Adverse effects include nausea, diarrhea, stomatitis, and peripheral neuropathy with prolonged use. Metronidazole has a disulfiram-like effect, and patients should be instructed to avoidalcohol. Although teratogenic in some animals, metronidazole has not been associated with this effect in humans.
A structurally similar agent, tinidazole, is a once-daily drug approved for treatment of trichomonas infection, giardiasis, and amebiasis. It also is active against anaerobic bacteria, but is not approved by the Food and Drug Administration (FDA) for treat-ment of anaerobic infections.