Nitroimidazoles are prodrugs composed of an imidazole ring with an attached nitro group. Nitroimidazoles are reduced within susceptible microorganisms, leading to free radical formation and disruption of DNA integrity. Metronidazole and tinidazole are the most used of the class and are active against both protozoa and anaerobic bacteria. These drugs are often used for intraabdominal and gynecologic infections. A disulfiram-like effect can occur with concurrent alcohol use. Other side effects include dysgeusia, peripheral neuropathy, urine discoloration, and seizures.

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Chemistry and Pharmacodynamics

Chemical structure

Nitroimidazoles are composed of an imidazole ring and an attached nitro group.

Chemical structure of metronidazole

Chemical structure of metronidazole:
Metronidazole is composed of an imidazole ring with a nitro group (NO2) attached.

Image: “Metronidazol” by NEUROtiker. License: Public Domain

Mechanism of action

  • Nitroimidazoles passively diffuse into the microbial cell.
  • Nitroreductases (produced by susceptible organisms) → reduce the nitro group on the molecule
  • Results in the production of:
    • Free radicals
    • Cytotoxic metabolites → interact with host DNA → strand breakage and destabilization of the DNA helix
  • Cell death occurs
  • Effect:
    • Bactericidal against anaerobic bacteria
    • Antiprotozoal


The following describes the pharmacokinetics for metronidazole (the prototype drug of the class) and tinidazole.


  • Almost completely absorbed when given orally 
  • Bioavailability > 90%


  • Distributed widely in tissues
  • Low protein binding (< 20%)
  • Crosses the blood–brain barrier

Metabolism and excretion

  • Extensively metabolized in the liver
  • Excreted mainly in the urine


Antimicrobial coverage

  • Anaerobic bacteria:
    • Helicobacter pylori 
    • Bacteroides
    • Clostridium (including C. difficile)
    • Gardnerella
  • Protozoa:
    • Giardia
    • Entamoeba
    • Trichomonas

Types of infections

  • Pseudomembranous colitis
  • Gynecologic infections (including bacterial vaginosis)
  • Amebiasis
  • Nongonococcal urethritis
  • Intraabdominal infections
  • Intracranial abscess

Adverse Effects and Contraindications

Adverse effects

  • GI upset
  • Disulfiram-like reaction with alcohol (due to inhibition of aldehyde dehydrogenase)
  • Dysgeusia (metallic taste) 
  • Peripheral neuropathy 
  • Headache
  • Dizziness 
  • Seizures
  • Urine discoloration (red-brown color)


  • Pregnancy (1st trimester)
  • Breastfeeding 
  • Severe hepatic impairment

Drug interactions

  • Ethanol-containing elixirs:
    • Cough syrups
    • IV trimethroprim–sulfamethoxazole
  • Disulfiram: can cause acute psychosis
  • ↓ Elimination of:
    • Lithium
    • Ergots
  • ↓ Liver metabolism of:
    • Phenytoin
    • Warfarin
    • Carbamazepine

Mechanism of Resistance

Metronidazole resistance is rare, but can occur by:

  • ↓ Rate of metronidazole reduction inside anaerobes
  • ↓ Uptake of the drug 
  • ↑ Efflux of drug from the cell
  • ↑ LDH activity
  • ↑ Activity of DNA repair enzymes
  • ↑ Oxygen-scavenging capabilities 

Comparison of Antibiotics

The following table compares several classes of antibiotics with anaerobic coverage:

Table: Comparison of several classes of antibiotics with anaerobic coverage
Drug classMechanism of actionEffectCoverage
  • Irreversibly bind penicillin-binding proteins
  • Inhibit cell wall synthesis
  • Gram-positives
  • Aerobic gram-negatives
  • Anaerobes
  • Inhibit DNA synthesis
  • Cause breakage of DNA
  • Gram-positives
  • Aerobic gram-negatives
  • Anaerobes
  • Atypical organisms
  • Reversibly bind to the 50S subunit
  • Inhibit bacterial protein synthesis
  • Gram-positives
  • Anaerobes
  • Produce free radicals
  • Cause breakage of DNA
  • Bactericidal
  • Antiprotozoal
  • Anaerobic bacteria
  • Protozoans
Antibiotic sensitivity chart

Antibiotic sensitivity:
Chart comparing the microbial coverage of different antibiotics for gram-positive cocci, gram-negative bacilli, and anaerobes.

Image by Lecturio. License: CC BY-NC-SA 4.0


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