Metronidazole was Originally Introduced to Treat Trichomonas Vaginalis, But is Currently Utilized to Treat a Variety of Anaerobic and Protozoal Infections (Clin Pharmacokinet, 1999) [MEDLINE]
Metabolism
Majority of Metronidazole and its Metabolites are Excreted in Urine and Feces
Less than 12% of Metronidazole is Excreted Unchanged in the Urine
Administration
Oral (PO)
Dose: XXXXXXX
Intravenous (IV)
Dose
Dosing q8hrs: 500 mg q8hrs
Historically-Used Dosing Interval
Dosing q12hrs: 500 mg q12hrs
Half-Life of 8 hrs (Similar to Ceftriaxone) with an Active Hydroxy Metabolite Which has a Half-Life of 11-13 hrs
Blood Concentrations at 12 hrs Exceed the Minimum Inhibitory Concentration (MIC) for Most Anaerobes (Including Bacteroides Species, Fusobacterium Species, Clostridium Species)
As Compared to q8hr Dosing, q12hr Dosing Results in the Following
Decreased Gastrointestinal Intolerance
Decreased Risk of Neurologic Toxicity (Peripheral Neuropathy, Encephalopathy, etc)
Decreased Risk of Leukopenia
Decreased Medication Dosing Burden for Patients and Nursing Staff
Decreased Drug Waste (Especially During Times of Shortage)
Decreased Hypothetical Potential for Non-nim-Mediated Mechanicals of Resistance
Decreased Cost
In a Retrospective Study of the Treatment of Anaerobic/Mixed Anaerobic Infections, the Use of q12hr Dosing Appears was Equivalent (in Terms of Clinical Cure) to q8hrs Dosing (Ther Adv Infect Dis, 2018) [MEDLINE]
Mean Duration of Antibiotic Therapy and Hospital Length of Stay were Comparable
In a Multicenter, Retrospective Study of Metronidazole Treatment of Anaerobic Bacteremia, q12hr Dosing Had No Difference in Mortality Rate, Length of Stay, or Escalation of Therapy, as Compared to q8hrs Dosing (Anaerobe, 2021)[MEDLINE]
Binding to Neural RNA, Inhibiting Protein Synthesis
Modulation of Inhibitory Neurotransmitter γ-Aminobutyric Acid Receptors within Cerebellar/Vestibular Systems
Reversible Mitochondrial Dysfunction
Vasogenic and Cytotoxic Edema
Median Onset of Neurotoxicity Has Been Reported to Be 28-54 Days (Clin Neuropharmacol, 2011) doi:10.1097/WNF.0b013e3182334b35 [MEDLINE] (J Neurol, 2020) [MEDLINE]
Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin Pharmacokinet. 1999 May;36(5):353-73. doi: 10.2165/00003088-199936050-00004 [MEDLINE]
Clinical efficacy of 12-h metronidazole dosing regimens in patients with anaerobic or mixed anaerobic infections. Ther Adv Infect Dis. 2018 May;5(3):57-62. doi: 10.1177/2049936118766462 [MEDLINE]
Three is a crowd: Clinical outcomes of a twice daily versus a thrice daily metronidazole dosing strategy from a multicenter study. Anaerobe. 2021 Oct;71:102378. doi: 10.1016/j.anaerobe.2021.102378 [MEDLINE]
Adverse Effects
Cerebellar ataxia following prolonged use of metronidazole: case report and literature review. Int J Infect Dis. 2008;12(6):e111-114. doi:10.1016/j.ijid.2008.03.006 [MEDLINE]
Anaphylaxis due to metronidazole with positive skin prick test. J Investig Allergol Clin Immunol. 2008;18(2):138-139 [MEDLINE]
Cerebellar ataxia following prolonged use of metronidazole: case report and literature review. Int J Infect Dis. 2008;12(6):e111-114. doi:10.1016/j.ijid.2008.03.006 [MEDLINE]
Metronidazole-induced central nervous system toxicity: a systematic review. Clin Neuropharmacol. 2011;34(6):241-247. doi:10.1097/WNF.0b013e3182334b35 [MEDLINE]
Metronidazole-induced encephalopathy: case report and review literature. Acta Neurol Taiwan. 2012;21(2):74-78 [MEDLINE]
Metronidazole-induced vertigo. Kaohsiung J Med Sci. 2013;29(12):695-696. doi:10.1016/j.kjms.2013.08.001 [MEDLINE]
Probable metronidazole induced serum sickness-like reaction in a paediatric patient. J Clin Pharm Ther. 2016;41(6):736-738. doi:10.1111/jcpt.12448 [MEDLINE]
Clinical and neuroradiological spectrum of metronidazole induced encephalopathy: our experience and the review of literature. J Clin Diagn Res. 2016;10(6):OE01-OE09. doi:10.7860/JCDR/2016/19032.8054 [MEDLINE]
