Indications
Clostridium Difficile Colitis (see Clostridium Difficile)
XXXXXXXXX
- xxx
XXXX
- xxx
Pharmacology
Nitroimidazole Antimicrobial
- 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]
- Contraindications to q12hr Dosing
- Central Nervous System Infection
- Clostridium Difficile Infection (see Clostridium Difficile)
- Parasitic/Amoebic Infection
Dose Adjustment
- Hepatic
- Dose Reduce in the Setting of Liver Disease
- Renal:
Use in Pregnancy (see Pregnancy)
- xxx
Use During Breast Feeding
- xxx
Adverse Effects
Allergic/Immunologic Adverse Effects
Anaphylaxis (see Anaphylaxis)
- Epidemiology
- Cases Have Been Reported (J Investig Allergol Clin Immunol, 2008) [MEDLINE]
- Clinical
- XXXX
Serum Sickness-Like Reaction (see xxxx)
- Epidemiology
- XXCases Have Been Reported (J Clin Pharm Ther, 2016) [MEDLINE]
- Clinical
- XXXX
Cardiovascular Adverse Effects
QT Prolongation without Definite Association with Torsade (see Torsade)
- Epidemiology
- No Definite Association with Torsade
Dermatologic Adverse Effects
Pruritus (Genital) (see xxxx)
- Epidemiology
- Occurs in 5% of Cases
- Clinical
- XXXX
Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) (see xxxx)
- Epidemiology
- XXXX
- Clinical
- XXXX
Gastrointestinal Adverse Effects
Abdominal Pain (see Abdominal Pain)
- Epidemiology
- Occurs in 4% of Cases
- Clinical
- XXXX
Acute Pancreatitis (see Acute Pancreatitis)
- Epidemiology
- Probable Association
Diarrhea (see Diarrhea)
- Epidemiology
- Occurs in 4% of Cases
- Clinical
- XXXX
Disulfiram-Like Reaction
- Epidemiology
- XXXX
- Clinical
- XXXX
Nausea (see Nausea and Vomiting)
- Epidemiology
- Occurs in 10-12% of Cases
- Clinical
- XXXX
Neurologic Adverse Effects
General Comments
- Proposed Mechanisms of Neurologic Toxicity
- 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]
- However, Some Cases Occur in <1 wk
- Risk Factors
- High Metronidazole Doses
- High Cumulative Metronidazole Dose
- Prolonged or Repeated Metronidazole Courses
Aseptic Meningitis (see Aseptic Meningitis)
- Epidemiology
- XXXX
- Clinical
- XXXX
Encephalopathy (see xxxx)
- Epidemiology
- Clinical* Encephalopathy/Delirium (see Encephalopathy and Delirium)
Headache (see Headache)
- Epidemiology
- Occurs in 18% of Cases
- Clinical
- XXXX
Neurocerebellar Toxicity (see xxxx)
- Epidemiology
- Diagnosis
- Brain Magnetic Resonance Imaging (MRI) (see Brain Magnetic Resonance Imaging)
- XXXXX
- Brain Magnetic Resonance Imaging (MRI) (see Brain Magnetic Resonance Imaging)
- Clinical
- Ataxia (see Ataxia)
- Treatment
- Discontinue Metronidazole: almost always results in resolution of symptoms and structural lesions
Optic Neuropathy (see xxxx)
- Epidemiology
- XXXX
- Clinical
- XXXX
Peripheral Neuropathy (see Peripheral Neuropathy)
- Epidemiology
- XXXX
- Clinical
- XXXX
Seizures (see Seizures)
- Epidemiology
- Clinical
- XXXX
Vertigo (see Vertigo)
- Epidemiology
- Clinical
- XXXX
Pulmonary Adverse Effects
Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia)
- Epidemiology
- XXXX
- Clinical
- XXXX
Reproductive Adverse Effects
Vaginitis (see xxxx)
- Epidemiology
- Occurs in 15% of Cases
- Clinical
- XXXX
Other Adverse Effects
- xxx
- xxx
- xxx
References
Administration
- 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]
- Metronidazole-induced cerebellar toxicity. Neurol Int. 2016;8(1):6365. doi:10.4081/ni.2016.6365 [MEDLINE]
- Metronidazole-induced encephalopathy. IDCases. 2019;18:e00639. doi:10.1016/j.idcr.2019.e00639 [MEDLINE]
- Metronidazole-induced encephalopathy: a systematic review. J Neurol. 2020;267(1):1-13. doi:10.1007/s00415-018-9147-6 [MEDLINE]