Merck Manual

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Professional Version



Dawn Merton Boothe

, DVM, PhD, Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University

Last full review/revision Nov 2015 | Content last modified Jun 2016

The 5-nitroimidazoles are a group of drugs that have both antiprotozoal and antibacterial activity. Nitroimidazoles with activity against trichomonads and amebae include metronidazole, tinidazole, nimorazole, flunidazole, and ronidazole. Metronidazole and nimorazole are effective in treatment of giardiasis, whereas dimetridazole, ipronidazole, and ronidazole control histomoniasis in poultry. Several nitroimidazoles have activity against trypanosomes. Metronidazole, ronidazole, and other nitroimidazoles are active against anaerobic bacteria. Metronidazole is the compound that has been the most studied and is discussed as the prototype of the group. Extra-label use of nitroimidazoles is prohibited in food animals in the USA.


Metronidazole has been used for many years in therapeutic management of trichomoniasis, giardiasis, and amebiasis. It is active against obligate anaerobic bacteria. It is not active against facultative anaerobes, obligate aerobes, or microaerophilic bacteria other than Campylobacter fetus. At concentrations readily attained in serum after PO or parenteral administration, metronidazole is active against Bacteroides fragilis, B melaninogenicus, Fusobacterium spp, and Clostridium perfringens and other Clostridium spp. It is generally less active against nonsporeforming, gram-positive bacilli such as Actinomyces, Propionibacterium, Bifidobacterium, and Eubacterium spp. Metronidazole is also somewhat less active against gram-positive cocci such as Peptostreptococcus and Peptococcus spp, but the less sensitive strains are usually not obligate anaerobes.

Metronidazole is bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentration. The precise mode of action is unclear, but reduction in an anaerobic environment yields a compound that then binds to DNA, causing loss of the helical structure, strand breakage, and impairment of DNA function. Only susceptible organisms (bacteria and protozoa) appear to be capable of metabolizing the drug.

The pharmacokinetic pattern of metronidazole generally follows that expected of a highly lipid-soluble basic drug. It is readily but variably absorbed from the GI tract (bioavailability 60%–100%), with serum concentrations peaking within 1–2 hr, and becomes widely distributed in all tissues. Metronidazole penetrates the blood-brain barrier and also attains therapeutic concentrations in abscesses and in empyema fluid. It is only slightly bound to plasma proteins. Biotransformation is quite extensive, and parent drug and metabolites are excreted by both the renal and biliary routes. The elimination half-life in dogs is ~4.5 hr, and in horses, 1.5–3.3 hr.

The principal clinical indications for metronidazole include the treatment of specific protozoal infections (amebiasis, trichomoniasis, giardiasis, and balantidiasis) and anaerobic bacterial infections such as those that may be seen in abdominal abscesses, peritonitis, empyema, genital tract infections, periodontitis, otitis media, osteitis, arthritis, and meningitis, and in necrotic tissue. Metronidazole has been successfully used to prevent infection after colonic surgery. Nitroimidazoles also act as radiosensitizers, and metronidazole has been used as an adjunct to the radiotherapy of solid tumors.

Adverse effects are not commonly associated with metronidazole. High doses may induce signs of neurotoxicity in dogs, such as tremors, muscle spasms, ataxia, and even convulsions. Reversible bone marrow depression has been reported. The drug should not be used in pregnant animals, particularly during the first trimester, although the evidence for carcinogenicity and mutagenicity is still tenuous. Metronidazole may produce a reddish brown discoloration of the urine due to unidentified pigments.

Recommended dose rates for metronidazole in dogs are 44 mg/kg, PO, followed by 22 mg/kg, qid, for anaerobic infections; 25 mg/kg, PO, bid, for giardiasis; and 66 mg/kg/day, PO, for trichomoniasis. Courses of therapy are generally 5–7 days. Both PO and IV preparations are available.

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