What is metronidazole used for?

Metronidazole Clinical Uses

Metronidazole is a nitroimidazole antibiotic used primarily to treat trichomoniasis, bacterial vaginosis, anaerobic bacterial infections, and protozoal infections including amebiasis and giardiasis. 1, 2

Primary Indications

Trichomoniasis

• Metronidazole 500 mg orally twice daily for 7 days is the preferred first-line regimen, achieving cure rates of approximately 90-95% 1, 2
• Alternative single-dose regimen: metronidazole 2 g orally as a one-time dose 1
• Metronidazole is the only oral medication available in the United States for treating trichomoniasis 1
• Sex partners must be treated simultaneously to prevent reinfection, and patients should abstain from sexual intercourse until both partners complete treatment and are asymptomatic 1, 2

Bacterial Vaginosis

• Metronidazole is effective for treating bacterial vaginosis, though topical metronidazole gel is considerably less effective for trichomoniasis (<50% cure rate) and should not be used for that indication 1
• For pregnant women with symptomatic bacterial vaginosis, metronidazole 250 mg orally three times daily for 7 days is recommended 1

Anaerobic Bacterial Infections

• Metronidazole is bactericidal against virtually all obligate anaerobic bacteria, particularly Gram-negative anaerobes including Bacteroides and Fusobacterium species 3, 4
• Highly effective for treating anaerobic infections of the chest, head, gastrointestinal tract, female genitourinary tract, and anaerobic septicemia 3
• Metronidazole is notably effective for treating anaerobic brain abscesses due to excellent central nervous system penetration 4
• Used for prophylaxis in elective colorectal surgery to prevent postoperative anaerobic infections 3, 5

Clostridium difficile Colitis

• Metronidazole is the preferred agent for treating C. difficile-induced pseudomembranous colitis due to similar efficacy to vancomycin but significantly lower cost 4, 5

Protozoal Infections

• Effective treatment for amebiasis caused by Entamoeba histolytica 3, 6, 5
• Effective for giardiasis caused by Giardia lamblia 3, 6, 5

Helicobacter pylori Eradication

• Metronidazole is used as part of combination regimens (typically with proton pump inhibitors, bismuth, and amoxicillin) for H. pylori eradication in patients with gastritis and duodenal ulcers 4

Special Population Considerations

Pregnancy

• Metronidazole is contraindicated during the first trimester of pregnancy 1
• After the first trimester, pregnant women can be treated with metronidazole 2 g orally as a single dose 1
• Multiple studies and meta-analyses have not demonstrated consistent associations between metronidazole use during pregnancy and teratogenic or mutagenic effects in infants 1
• Trichomoniasis during pregnancy is associated with adverse outcomes including premature rupture of membranes, preterm delivery, and low birthweight 1

HIV Infection

• Patients with HIV infection should receive the same metronidazole treatment regimens as HIV-negative individuals 1, 2

Hepatic Impairment

• Patients with severe hepatic disease metabolize metronidazole slowly, resulting in drug accumulation; doses below usual recommendations should be administered cautiously 7
• Liver disease decreases metronidazole clearance and dosage reduction is recommended 8

Renal Impairment

• Metronidazole pharmacokinetics are unaffected by acute or chronic renal failure, hemodialysis, or continuous ambulatory peritoneal dialysis 8
• Dosage alterations are unnecessary in renal dysfunction, though metabolite elimination is reduced 8

Treatment Failure Management

Trichomoniasis Treatment Failure

• For first treatment failure: re-treat with metronidazole 500 mg twice daily for 7 days 1, 2
• For repeated treatment failure: administer metronidazole 2 g once daily for 3-5 days 1, 2
• If treatment continues to fail after the 3-5 day regimen and reinfection has been excluded, consult with an infectious disease specialist and consider susceptibility testing 1, 2
• Some T. vaginalis strains have diminished susceptibility to metronidazole but most respond to higher doses 1

Important Drug Interactions and Precautions

Alcohol Interaction

• Alcoholic beverages must be avoided during metronidazole therapy and for at least one day afterward due to risk of disulfiram-like reactions causing abdominal cramps, nausea, vomiting, headaches, and flushing 7
• Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently 7

Anticoagulant Interaction

• Metronidazole potentiates the anticoagulant effect of warfarin and other oral coumarins, resulting in prolonged prothrombin time 7

Other Drug Interactions

• Phenytoin or phenobarbital may accelerate metronidazole elimination, reducing plasma levels 7
• Cimetidine may prolong metronidazole half-life and decrease plasma clearance 7
• In patients on high-dose lithium, metronidazole therapy has been associated with elevated serum lithium and potential lithium toxicity; serum lithium and creatinine should be monitored 7

Pharmacokinetic Advantages

• Oral bioavailability exceeds 90% for tablets, with absorption unaffected by infection 8
• Metronidazole distributes widely with low protein binding (<20%) and reaches 60-100% of plasma concentrations in most tissues, including the central nervous system 8, 4
• The hydroxy metabolite has 30-65% biological activity with a longer elimination half-life than the parent compound 8, 5
• Post-antibiotic effect extends beyond 3 hours after concentration falls below the minimum inhibitory concentration 8

Adverse Effects and Safety Concerns

• Generally well tolerated with infrequent and minimal side effects 5
• Reversible neutropenia may occur; total and differential leukocyte counts are recommended before and after therapy, especially if a second course is necessary 7
• Peripheral neuropathy can develop 6
• Mutagenicity and carcinogenicity have been demonstrated in some animal studies, though follow-up studies of treated patients have not revealed increased cancer incidence 6
• Metronidazole should only be used for proven or strongly suspected bacterial or protozoal infections to reduce development of drug-resistant bacteria 7