Generic Name

Metronidazole

Mechanism

• Metronidazole is a pro‑drug that is reduced in anaerobic organisms and select protozoa by nitroreductase enzymes.
• Reduction generates radical nitro ions that damage microbial DNA strand breaks and inhibit macromolecule synthesis.
• The drug is ineffective against bacteria that possess oxygen‑dependent metabolic pathways, explaining its specificity for anaerobes (e.g., *Bacteroides*, *Clostridium*, *Peptostreptococcus*) and protozoa (e.g., *Giardia*, *Trichomonas*, *Entamoeba*).

Pharmacokinetics

• Absorption: Rapid and almost complete (≈ 96–98 %) when given orally or IV.
• Distribution: Widely distributed; high concentrations in GI tract, uterus, placenta, and CNS. Penetration into cystic fluid and abscesses is modest.
• Metabolism: Primarily glucuronidation in the liver; also undergoes conjugation in the intestine.
• Elimination: Excreted unchanged in urine (≈ 85 %); half‑life 8–11 h.
• Drug interactions: Inhibits CYP2C9/CYP2C19; decreases metabolism of warfarin, phenytoin, and sulfamethoxazole/trimethoprim – risk of toxicity.

Indications

• Anaerobic bacterial infections: appendicitis, diverticulitis, intra‑abdominal abscesses, peritonitis.
• Protozoal infections:
• *Giardia lamblia* (asymptomatic or symptomatic intestinal disease)
• *Trichomonas vaginalis* (vaginal trichomoniasis)
• *Entamoeba histolytica* (amoebic dysentery and liver abscess)
• Intra‑abdominal sepsis: used in combination with broad‑spectrum agents.
• Dental infections & oral abscesses.

Contraindications

• Contraindications:
• Hypersensitivity to nitroimidazole class.
• Severe hepatic impairment (due to hepatic glucuronidation).
• Warnings:
• Teratogenic and abortifacient; avoid during pregnancy.
• Neurotoxicity: risk of peripheral neuropathy, cerebellar dysfunction, and seizures with prolonged high‑dose therapy.
• Alcohol interaction: disulfiram‑like reaction (nausea, vomiting, flushing) – advise complete avoidance of alcohol.
• Liver disease: dose adjustment may be required.

Dosing

*For children:* 15–20 mg/kg/day divided q8h, max 1 g/day.
• IV infusion over 1–2 h to minimize headache and nausea.
• Adjust for renal dysfunction: >60 mL/min: no adjustment; 30–60 mL/min: reduce dose by 50 %; <30 mL/min: further dose reduction.

Adverse Effects

• Common (≥1 %): nausea, vomiting, metallic taste, abdominal pain, headache, diarrhea.
• Serious:
• Peripheral neuropathy (tinnitus, numbness) – dose‑dependent.
• Severe CNS effects: ataxia, seizures, myoclonic movements (especially with high doses or prolonged therapy).
• Hypersensitivity rash, anaphylaxis.
• Liver enzyme elevations (monitor LFTs).
• Alcohol‑induced disulfiram reaction.

Monitoring

• Liver Function Tests (LFTs): baseline and every 4–6 weeks for prolonged therapy.
• Renal Function: baseline, then monthly if creatinine >1 mg/dL.
• Neurologic status: at baseline and throughout therapy for signs of neuropathy or CNS toxicity.
• Prothrombin Time/INR: if co‑administered with warfarin.
• Pregnancy status: confirm trimester; discuss conception planning.

Clinical Pearls

• Avoid Alcohol: Even brief exposure during treatment can precipitate an acute, painful reaction; counsel patients to abstain for at least 48 h after completing therapy.
• Single‑dose Trichomoniasis Regimen: 2 g PO is highly efficacious and improves compliance compared to the 7‑day BID schedule.
• Pericardial/Brain Abscesses: Metronidazole penetrates abscess cavities, making it the drug of choice for anaerobic coverage.
• Pregnancy Category: C; use only when benefits outweigh risks; switch to clindamycin if possible.
• Combination Therapy: When treating polymicrobial intra‑abdominal infection, pair Metronidazole with a β‑lactam/β‑lactamase inhibitor or carbapenem for optimal anaerobic coverage.
• Dose Reduction in Elderly: Monitor for neurotoxicity; consider lower starting doses or extended‑interval dosing.

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• Key takeaways: Metronidazole’s unique ability to selectively target anaerobic bacteria and protozoa, combined with its excellent oral bioavailability, makes it indispensable for treating a broad spectrum of infections. However, careful attention to dosing, drug interactions, pregnancy precautions, and adverse effect monitoring is essential for safe, effective therapy.