Metronidazole Drug Classification
Metronidazole is a synthetic nitroimidazole antimicrobial agent with selective activity against anaerobic bacteria and certain protozoa. 1, 2
Drug Class and Mechanism
Metronidazole belongs to the nitroimidazole class of antimicrobials, which are synthetic antibacterial and antiprotozoal compounds 1, 2, 3
The drug exerts its bactericidal effects through a unique mechanism: once it enters anaerobic organisms by passive diffusion, it undergoes reduction in the cytoplasm, forming short-lived nitroso free radicals that interact with DNA, leading to DNA strand breakage, inhibition of DNA synthesis, and ultimately bacterial death 1, 4
This mechanism requires an anaerobic environment for activation, which explains its selective activity against obligate anaerobes 1, 5
Spectrum of Antimicrobial Activity
Antiprotozoal Activity
Metronidazole is highly effective against protozoan infections including Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia 6, 7
For trichomoniasis, metronidazole achieves cure rates of 90-95% with recommended regimens 6
Antibacterial Activity
The drug demonstrates potent activity against most Gram-negative anaerobes, particularly Bacteroides fragilis (the most resistant anaerobic bacterium) and Fusobacterium species 4, 7
Gram-positive anaerobes including Clostridium species and peptostreptococci are generally susceptible, though resistant isolates occur more frequently than with Gram-negative anaerobes 7
Metronidazole is bactericidal at low concentrations, producing a 2-5 log decrease in colony-forming units within one hour 4
Important Limitations
Metronidazole has NO activity against aerobic bacteria, requiring combination with other antimicrobials (typically aminoglycosides) for mixed aerobic-anaerobic infections 4, 5
Occasional anaerobic cocci, some nonsporulating gram-positive bacilli, and Propionibacterium species are naturally resistant 4
Clinical Applications
The CDC recommends metronidazole as first-line therapy for trichomoniasis (2 g single dose or 500 mg twice daily for 7 days) 6
For bacterial vaginosis, metronidazole 500 mg twice daily for 7 days is recommended 8
The drug is effective for anaerobic infections including brain abscesses, intra-abdominal sepsis, pelvic infections, and Clostridium difficile colitis (though now relegated to alternative status when vancomycin/fidaxomicin unavailable) 8, 7
Key Pharmacologic Properties
Oral bioavailability exceeds 90% with nearly complete absorption 3
The drug achieves excellent tissue penetration, reaching 60-100% of plasma concentrations in most tissues including the central nervous system 3, 5
Elimination half-life averages 8 hours in healthy adults, with minimal protein binding (<20%) 1, 3
A critical safety concern is the risk of cumulative and potentially irreversible neurotoxicity with repeated or prolonged courses, as warned by the Infectious Diseases Society of America 8