Metronidazole - Complete Drug Profile

Drug Class & Mechanism

• Pyruvate-ferredoxin oxidoreductase (PFOR) produces electrons that reduce ferredoxin, which donates electrons to metronidazole
• Oxygen competes with metronidazole for electrons - this is why it does NOT work against aerobes
• Goodman & Gilman's Pharmacological Basis of Therapeutics

Formulations Available

• Harriet Lane Handbook 23rd Ed.

Uses and Dosages

1. Protozoal Infections

• Mild to moderate/severe intestinal infection: 750 mg PO TID x 10 days (or 500 mg IV q6h x 10 days) + luminal amebicide
• Hepatic abscess / extraintestinal: 750 mg PO TID x 10 days - cures >95% of uncomplicated liver abscesses
• Children: 35-50 mg/kg/24hr PO divided q8h x 10 days; max 750 mg/dose

• Adults: 250 mg PO TID x 5-7 days
• Children: 15-30 mg/kg/24hr divided TID x 5-7 days; max 750 mg/24hr

• Adults: 2 g PO single dose (preferred) OR 500 mg BID x 7 days
• Children <45 kg: 45 mg/kg/24hr divided TID x 7 days; max 2000 mg/24hr
• Treat sexual contacts simultaneously. Metronidazole gel NOT recommended (only ~50% cure rate vs >84% with oral)
• Katzung Basic & Clinical Pharmacology 16th Ed.; Harrison's Internal Medicine 22nd Ed.

2. Anaerobic Bacterial Infections

• Adults: 7.5 mg/kg IV/PO q6h (≈500 mg/dose) x 7-10 days; max 4 g/24hr
  • Loading dose for IV: 15 mg/kg over 1 hr, followed by maintenance
• Children (infant/child/adolescent): 30-50 mg/kg/24hr PO divided q8h; max 2250 mg/24hr
• Neonates: Loading dose 15 mg/kg x 1, then maintenance by postmenstrual age (PMA):
  • PMA 24-25 wk: 7.5 mg/kg q24h
  • PMA 28-33 wk: 7.5 mg/kg q12h
  • PMA 34-40 wk: 7.5 mg/kg q8h
  • PMA >40 wk: 7.5 mg/kg q6h

• Harriet Lane Handbook 23rd Ed.; Bailey & Love's Surgery 28th Ed.

3. Bacterial Vaginosis (BV)

• Adults: 500 mg PO BID x 7 days OR vaginal gel 0.75% (37.5 mg) intravaginally every night x 5 days OR vaginal gel 1.3% x 1 dose
• Oral and vaginal regimens have similar cure rates at 4 weeks; vaginal gel has fewer GI side effects
• Tintinalli's Emergency Medicine; Harriet Lane Handbook 23rd Ed.

4. Clostridium difficile Infection (CDI)

• Adults (mild CDI): 500 mg PO TID x 10-14 days (less preferred than vancomycin for severe CDI)
  • Vancomycin is superior for severe CDI (response rate: vancomycin 79% vs metronidazole 66%)
  • IV metronidazole (500 mg TID) used when patients cannot tolerate oral medications, as it accumulates to bactericidal levels in the inflamed colon
• Children: 30 mg/kg/24hr divided q6h
• Sleisenger & Fordtran's GI Disease; Goodman & Gilman's

5. Helicobacter pylori (part of combination regimens)

• Red Book 2021

6. Surgical Prophylaxis (Colorectal/Abdominal/Pelvic)

• Bailey & Love's Short Practice of Surgery 28th Ed.

7. Rosacea (Topical)

• Topical gel 0.75% or 1% applied BID to affected areas
• Topical cream 0.75% or 1% applied once or twice daily
• Mechanism in rosacea: anti-inflammatory rather than antimicrobial
• Fitzpatrick's Dermatology; Harriet Lane Handbook 23rd Ed.

8. Other Uses

• Oral/dental infections - anaerobic coverage, often with amoxicillin
• Bone and joint infections - anaerobic component (prolonged course)
• Endocarditis and septicemia - due to anaerobic bacteria
• Respiratory tract infections - lung abscess, aspiration pneumonia (anaerobic component)
• Crohn's disease - adjunctive use; reduces perianal disease activity
• Gynecologic infections (PID, postoperative) - combination therapy

Pharmacokinetics

• Dose adjustment required in severe hepatic impairment (reduced clearance)
• End-stage renal disease: slow excretion of metabolites; monitor for toxicity
• Crosses the placenta (use with caution, especially in 1st trimester)
• Goodman & Gilman's

Side Effects

Common (GI - most frequent)

• Nausea (most common; ~30% with standard dosing)
• Metallic or bitter taste
• Dry mouth
• Abdominal cramping / discomfort
• Vomiting, diarrhea
• Weight loss

Neurological (dose-related, usually reversible)

• Headache, dizziness, vertigo
• Peripheral neuropathy (burning/tingling in hands and feet) - with prolonged use
• Ataxia, incoordination
• Seizures / convulsions (rare; warrant drug discontinuation)
• Encephalopathy (rare but serious; neuroimaging shows reversible lesions in cerebellum/brainstem)
• Confusion, psychosis (rare)
• Optic neuropathy (rare)

Genitourinary

• Dysuria, cystitis
• Sense of pelvic pressure
• Dark/reddish-brown urine (harmless pigment)

Hematological

• Leukopenia (mild; more risk in patients with pre-existing blood dyscrasias)

Dermatological

• Urticaria, flushing, rash
• Rarely: Stevens-Johnson syndrome / toxic epidermal necrolysis

Superinfection

• Worsening candidiasis (vaginal or oral thrush) - may require antifungal treatment
• Goodman & Gilman's; Yamada's Textbook of Gastroenterology; Mayo Clinic

Key Drug Interactions

Contraindications and Cautions

• First trimester of pregnancy - avoid (carcinogenicity in animal studies; use only if clearly necessary)
• History of blood dyscrasias - caution
• Severe hepatic impairment - dose reduction needed
• Known hypersensitivity to nitroimidazoles
• Concurrent disulfiram use

Resistance

• Impaired oxygen scavenging (raises local O2, reducing activation)
• Decreased levels of PFOR and ferredoxin
• Higher doses may still overcome low-level resistance
• Goodman & Gilman's