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# Metronidazole
## Overview
Metronidazole is an antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of symptomatic trichomoniasis.
* **Amoebiasis:** Treatment of amoebic intestinal infections (amoebic dysentery) and amoebic liver abscess.
* **Giardiasis:** Treatment of giardiasis.
* **Anaerobic bacterial infections:** Treatment of serious anaerobic bacterial infections (e.g., intra-abdominal infections, gynecologic infections, skin and soft tissue infections, lower respiratory tract infections, bone and joint infections, CNS infections, endocarditis, bacteremia).
* **_Clostridioides difficile_ infection (CDI):** Treatment of _C. difficile_ associated diarrhea. (Note: Oral vancomycin is often preferred for initial episodes).
* **Surgical prophylaxis:** Prophylaxis in specific surgical procedures (e.g., colorectal surgery).
* **_Helicobacter pylori_ eradication:** Part of combination therapy for _H. pylori_ eradication.
## Adult Dosing
Dosing varies significantly by indication. Common regimens include:
* **Bacterial vaginosis:** 500 mg orally twice daily for 7 days, OR 2 g orally as a single dose.
* **Trichomoniasis:** 2 g orally as a single dose, OR 250 mg orally three times daily for 7 days, OR 375 mg orally twice daily for 7 days.
* **Amoebiasis:**
* Intestinal: 500-750 mg orally three times daily for 5-10 days.
* Hepatic abscess: 500-750 mg orally three times daily for 5-10 days.
* **Giardiasis:** 250 mg orally three times daily for 5-7 days.
* **Anaerobic bacterial infections:** 500 mg IV or orally every 8 hours. Duration varies (e.g., 7-10 days or longer).
* **_C. difficile_ infection:** 250-500 mg orally four times daily for 10-14 days. (Consider higher dose for severe disease, though oral vancomycin is often preferred).
* **Surgical prophylaxis:** 1 g IV 1-2 hours before surgery, OR 500 mg orally/IV every 8 hours starting pre-operatively and continued post-operatively for up to 24 hours.
* **_H. pylori_ eradication:** Typically 500 mg orally twice daily in combination with other agents for 10-14 days.
Maximum dose: Generally 4 g per day for IV administration. For oral use, the maximum dose depends on the indication and clinical judgment, but exceeding 2 g/day is less common outside of specific acute indications.
## Pediatric Dosing
Dosing is weight-based and indication-specific.
* **Bacterial vaginosis:** Not typically used in pediatrics.
* **Trichomoniasis:** Not typically used in pediatrics.
* **Amoebiasis:**
* Intestinal: 35-50 mg/kg/day orally divided into 3 doses for 5-10 days (maximum 750 mg/dose).
* Hepatic abscess: 35-50 mg/kg/day orally or IV divided into 3 doses for 5-10 days (maximum 750 mg/dose).
* **Giardiasis:** 15-30 mg/kg/day orally divided into 3 doses for 5-7 days (maximum 250 mg/dose).
* **Anaerobic bacterial infections:**
* Oral: 15-30 mg/kg/day divided into 3 doses (maximum 750 mg/dose).
* IV: 7.5 mg/kg every 8 hours OR 15 mg/kg every 12 hours (maximum 15 mg/kg or 1 g per dose).
* **_C. difficile_ infection:** 10-20 mg/kg/day orally divided into 3-4 doses for 10-14 days (maximum 250 mg/dose).
## Dose Adjustments
* **Renal impairment:** No dose adjustment typically needed. However, for IV use, prolonged high doses may lead to accumulation of metabolites.
* **Hepatic impairment:** Dose reduction may be necessary in severe hepatic impairment due to reduced metabolism. Consider halving the usual dose in severe cases.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Concurrent use of disulfiram (within the last 2 weeks).
* Concurrent use of alcohol.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal pain, metallic taste, headache, dizziness.
* **Serious:** Peripheral neuropathy (especially with prolonged use or high doses), seizures, encephalopathy, ataxia, Stevens-Johnson syndrome, toxic epidermal necrolysis, severe allergic reactions, pancreatitis, dark urine (harmless).
* **_C. difficile_ associated diarrhea:** Although used to treat CDI, metronidazole can sometimes cause or exacerbate diarrhea.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, shortness of breath). Avoid alcohol during treatment and for at least 72 hours after discontinuation.
* **Disulfiram:** Psychotic reactions can occur. Avoid concurrent use.
* **Warfarin:** Potentiates anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole may increase serum lithium levels, potentially leading to toxicity. Monitor lithium levels.
* **Phenytoin, Phenobarbital:** May decrease metronidazole efficacy.
* **Cyclosporine:** Metronidazole may increase cyclosporine levels. Monitor cyclosporine levels.
* **5-Fluorouracil (5-FU):** Metronidazole may increase toxicity of 5-FU.
## Monitoring
* **Clinical response:** Assess for improvement in signs and symptoms of infection.
* **Adverse effects:** Monitor for neurological symptoms (neuropathy, dizziness, confusion), gastrointestinal distress, and hypersensitivity reactions.
* **INR:** If patient is on warfarin.
* **Lithium levels:** If patient is on lithium.
## Clinical Pearls
* The metallic taste is a common and often bothersome side effect.
* To minimize GI upset, metronidazole can be taken with food.
* Use with caution in patients with CNS disorders.
* Discontinue if signs of peripheral neuropathy or encephalopathy develop.
* Advise patients to avoid alcohol during and for at least 72 hours after treatment.
* When treating _C. difficile_, oral vancomycin is often preferred for initial episodes, especially severe ones, as it has better efficacy and lower recurrence rates.
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*This information is intended for clinical use and is not a substitute for professional medical advice. Always consult with a qualified healthcare provider and refer to the most current prescribing information before making any treatment decisions.*
