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The Journal of Antimicrobial... Feb 2018Metronidazole, a nitroimidazole, remains a front-line choice for treatment of infections related to inflammatory disorders of the gastrointestinal tract including... (Review)
Review
Metronidazole, a nitroimidazole, remains a front-line choice for treatment of infections related to inflammatory disorders of the gastrointestinal tract including colitis linked to Clostridium difficile. Despite >60 years of research, the metabolism of metronidazole and associated cytotoxicity is not definitively characterized. Nitroimidazoles are prodrugs that are reductively activated (the nitro group is reduced) under low oxygen tension, leading to imidazole fragmentation and cytotoxicity. It remains unclear if nitroimidazole reduction (activation) contributes to the cytotoxicity profile, or whether subsequent fragmentation of the imidazole ring and formed metabolites alone mediate cytotoxicity. A molecular mechanism underpinning high level (>256 mg/L) bacterial resistance to metronidazole also remains elusive. Considering the widespread use of metronidazole and other nitroimidazoles, this review was undertaken to emphasize the structure-cytotoxicity profile of the numerous metabolites of metronidazole in human and murine models and to examine conflicting reports regarding metabolite-DNA interactions. An alternative hypothesis, that DNA synthesis and repair of existing DNA is indirectly inhibited by metronidazole is proposed. Prokaryotic metabolism of metronidazole is detailed to discuss new resistance mechanisms. Additionally, the review contextualizes the history and current use of metronidazole, rates of metronidazole resistance including metronidazole MDR as well as the biosynthesis of azomycin, the natural precursor of metronidazole. Changes in the gastrointestinal microbiome and the host after metronidazole administration are also reviewed. Finally, novel nitroimidazoles and new antibiotic strategies are discussed.
Topics: Animals; Anti-Infective Agents; Drug Resistance, Bacterial; Humans; Metronidazole; Mice
PubMed: 29077920
DOI: 10.1093/jac/dkx351 -
The Medical Clinics of North America May 1988Metronidazole is a highly effective therapy for anaerobic infections and a variety of protozoal and parasitic diseases. Its pharmacokinetics, toxicities, and unique mode... (Review)
Review
Metronidazole is a highly effective therapy for anaerobic infections and a variety of protozoal and parasitic diseases. Its pharmacokinetics, toxicities, and unique mode of action are reviewed in detail. Indications for use and respective dosages are suggested.
Topics: Bacteria, Anaerobic; Bacterial Infections; Humans; Metronidazole; Protozoan Infections
PubMed: 3280909
DOI: 10.1016/s0025-7125(16)30761-1 -
The Australian & New Zealand Journal of... Aug 1987
Review
Topics: Breast Feeding; Carcinogens; Female; Humans; Metronidazole; Mutagens; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Teratogens; Vaginitis
PubMed: 3325019
DOI: 10.1111/j.1479-828x.1987.tb00994.x -
The Johns Hopkins Medical Journal Aug 1981
Review
Topics: Anaerobiosis; Bacteria; Bacterial Infections; Endocarditis, Bacterial; Humans; Kinetics; Metronidazole
PubMed: 7019533
DOI: No ID Found -
Annales de Dermatologie Et de... Sep 2001Metronidazole was first introduced for the treatment of trichomoniasis. Now, its therapeutics use has subsequently been expanded to include protozoal and anaerobic... (Review)
Review
Metronidazole was first introduced for the treatment of trichomoniasis. Now, its therapeutics use has subsequently been expanded to include protozoal and anaerobic infections. Oral administration is recommended: rosacea, perioral dermatitis, Helicobacter pylori, Trichomonas vaginalis and Giardia lamblia infections and bacterial vaginosis. Metronidazole given orally is absorbed almost completely. Metronidazole has limited plasma protein binding but can reach very favourable tissue distribution, including central nervous system and placenta. This drug is extensively metabolised by the liver to form 5 oxydative metabolites. The majority of this drug and metabolites are excreted in urine and feces. The half-life is 6 to 10 hours. The recommended dose is 500 mg three time per day and an adaptation is necessary in renal insufficiency. Metronidazole is well tolerated when administered in dosages of less than 2 g per day. Some adverse reactions appear to be related to the high dosages and treatment duration. Drug interactions with alcohol, warfarin and phenytoin have been reported. Mutagenesis and cancerogenesis is only described in mouse. Resistance, both clinical and microbiological, has been described only rarely.
Topics: Anti-Infective Agents; Drug Interactions; Humans; Metronidazole
PubMed: 11590342
DOI: No ID Found -
Pediatric Clinics of North America Feb 1983
Review
Topics: Adolescent; Adult; Bacterial Infections; Child; Child, Preschool; Humans; Metronidazole
PubMed: 6338471
DOI: 10.1016/s0031-3955(16)34321-8 -
Infection Control : IC Oct 1986
Review
Topics: Bacterial Infections; Humans; Metronidazole
PubMed: 3536782
DOI: 10.1017/s0195941700065152 -
The Medical Clinics of North America Jan 1982
Review
Topics: Absorption; Bacteria; Bacterial Infections; Carcinogens; Humans; Metronidazole; Mutagens
PubMed: 7038323
DOI: 10.1016/s0025-7125(16)31446-8 -
Mutation Research Jun 2002Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs. MTZ is potentially... (Review)
Review
Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs. MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals. However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans. As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor. Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.
Topics: Animals; Anti-Infective Agents; Carcinogenicity Tests; Carcinogens; DNA Damage; Humans; Metronidazole; Molecular Structure; Mutagenicity Tests; Mutagens
PubMed: 12052431
DOI: 10.1016/s1383-5742(02)00007-8 -
Ugeskrift For Laeger Oct 1972
Review
Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Female; Fetal Death; Humans; Metronidazole; Pregnancy; Pregnancy Complications; Time Factors; Trichomonas Vaginitis
PubMed: 4569350
DOI: No ID Found