Metronidazole Coverage
Metronidazole adds coverage specifically for anaerobic bacteria, including both Gram-negative anaerobes (particularly Bacteroides fragilis group and Fusobacterium species) and Gram-positive anaerobes (Clostridium, Peptostreptococcus, and Eubacterium species). 1
Primary Spectrum of Activity
Gram-Negative Anaerobes
- Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus) - metronidazole is the most active antimicrobial agent against B. fragilis, which is the most resistant of anaerobic bacteria 2, 1, 3
- Fusobacterium species 1
- Prevotella species (P. bivia, P. buccae, P. disiens) 1
Gram-Positive Anaerobes
- Clostridium species (including C. perfringens) 1, 3
- Peptostreptococcus species 1
- Peptococcus species 1
- Eubacterium species 1
Mechanism and Bactericidal Activity
Metronidazole demonstrates rapid bactericidal activity against susceptible anaerobes, with kill-curve studies showing a 2 to 5 log decrease in colony forming units of B. fragilis and C. perfringens within one hour 3. The drug is usually bactericidal at low concentrations and achieves bactericidal levels in serum, cerebrospinal fluid, tissue, and pus from abscesses 1, 4.
Critical Clinical Context
What Metronidazole Does NOT Cover
Metronidazole has NO clinically relevant activity against facultative anaerobes or obligate aerobes 1. This means it must be combined with other antimicrobial agents (typically aminoglycosides, fluoroquinolones, or cephalosporins) when treating mixed aerobic-anaerobic infections 2, 3.
When Metronidazole is Added to Regimens
Intra-abdominal infections: Metronidazole is combined with agents covering Gram-negative aerobes (cephalosporins, fluoroquinolones, or aminoglycosides) for infections involving the distal small bowel, appendix, or colon 2
Necrotizing soft tissue infections: For polymicrobial necrotizing fasciitis, metronidazole provides the greatest anaerobic spectrum against enteric Gram-negative anaerobes, though it is less effective than clindamycin against Gram-positive anaerobic cocci 2
Pelvic infections: Metronidazole combined with tobramycin or other aminoglycosides provides coverage for the mixed aerobic-anaerobic flora typical of postpartum endomyometritis, tubo-ovarian abscess, and pelvic cellulitis 2, 5
Animal/human bites: Metronidazole or clindamycin is added to provide anaerobic coverage when treating bite wounds 2
Resistance Considerations
Resistance to metronidazole is uncommon but documented. Bacteroides fragilis group isolates have demonstrated substantial resistance to clindamycin, cefotetan, cefoxitin, and quinolones, making metronidazole a preferred agent in contexts where B. fragilis is likely 2. The drug maintains undiminished antimicrobial activity and is considered by many clinicians to be the "gold standard" against which other anaerobic agents should be compared 6.