Metronidazole Dosing and Duration for Bacteroides fragilis Infections
For Bacteroides fragilis infections, metronidazole should be dosed at 500 mg orally three times daily for 10 days, though this is now considered a second-line option after vancomycin or fidaxomicin for most anaerobic infections. 1
Recommended Dosing Regimens by Route of Administration
Oral Administration
- For non-severe infections: 500 mg three times daily for 10 days 1
- Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 1
Intravenous Administration
- Loading dose: 15 mg/kg infused over one hour (approximately 1 g for a 70-kg adult) 2
- Maintenance dose: 7.5 mg/kg infused over one hour every six hours (approximately 500 mg for a 70-kg adult) 2
- Alternative regimen for serious intra-abdominal/pelvic infections: 1 g IV once daily, which appears to be as efficacious as multiple daily dosing 3
- Duration: 7-10 days for most infections; longer treatment may be required for bone/joint, lower respiratory tract, and endocardial infections 2
Treatment Considerations Based on Infection Severity
Non-severe Infections
- Metronidazole 500 mg orally three times daily for 10 days is acceptable when vancomycin or fidaxomicin are unavailable 1
- Metronidazole has excellent activity against B. fragilis with minimal inhibitory concentrations (MIC) of 0.16-2.5 μg/ml 4
Severe/Fulminant Infections
- For fulminant infections (hypotension, shock, ileus, megacolon), intravenous metronidazole (500 mg every 8 hours) should be administered together with oral vancomycin 1
- In patients with ileus where oral medications cannot reach the colon, IV metronidazole is particularly important 1
Special Populations
Patients with Hepatic Impairment
- Patients with severe hepatic disease metabolize metronidazole slowly, resulting in drug accumulation 2
- Lower doses should be administered with close monitoring of plasma levels and toxicity 2
Elderly Patients
- Pharmacokinetics may be altered in elderly patients 2
- Monitoring of serum levels may be necessary to adjust dosage accordingly 2
Important Clinical Considerations
- Metronidazole is no longer first-line therapy for most anaerobic infections including Clostridioides difficile infection (CDI) 1
- Vancomycin or fidaxomicin are now preferred for initial treatment of CDI and other anaerobic infections 1
- Metronidazole has excellent penetration into abscess cavities and crosses the blood-brain barrier, making it effective for treating anaerobic brain abscesses 5
- Haemin deprivation can render even resistant B. fragilis strains susceptible to metronidazole, which may be clinically relevant in certain infection sites 6
Potential Pitfalls and Caveats
- Avoid prolonged or repeated courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1
- In patients with continuous nasogastric aspiration, sufficient metronidazole may be removed to reduce serum levels 2
- Metronidazole resistance in B. fragilis does occur, though it remains relatively uncommon 6
- Pulse dosing (frontloaded sequential bolus injections) may be as effective as standard dosing against both susceptible and resistant Bacteroides strains 7