Metronidazole Does NOT Cover Staphylococcus aureus
Metronidazole has no activity against Staphylococcus aureus and should never be used as monotherapy for staphylococcal infections. 1, 2, 3
Spectrum of Activity
Metronidazole's antimicrobial coverage is limited to:
- Anaerobic bacteria only: Primarily Gram-negative anaerobes (Bacteroides, Fusobacterium species) and some Gram-positive anaerobes (Peptostreptococci, Clostridia) 2, 3
- No aerobic coverage: Metronidazole completely lacks activity against all aerobic pathogens, including S. aureus 1, 3
- Protozoal infections: Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis 2, 4
Why This Matters Clinically
The IDSA explicitly states that metronidazole must always be combined with agents covering aerobic gram-positive organisms when treating mixed infections 1. This is because:
- S. aureus is an aerobic organism that metronidazole cannot target 2, 3
- Clinical guidelines consistently pair metronidazole with other antibiotics (ceftriaxone, ciprofloxacin, ampicillin) specifically to cover the aerobic pathogens that metronidazole misses 5
Common Clinical Scenarios
For skin and soft tissue infections with suspected S. aureus:
- Use clindamycin instead of metronidazole, as it covers both S. aureus and anaerobes 1
- If metronidazole is used for anaerobic coverage, add vancomycin, cefazolin, or oxacillin for staphylococcal coverage 5
For intra-abdominal infections:
- Metronidazole is combined with ceftriaxone or ciprofloxacin to provide the missing aerobic coverage 5
- The metronidazole component targets Bacteroides fragilis and other anaerobes, while the partner drug covers aerobes including S. aureus 5
Critical Pitfall to Avoid
Never assume metronidazole provides broad-spectrum coverage. Its role is exclusively for anaerobic bacteria in polymicrobial infections 3, 4. Using it alone for any infection where S. aureus is a consideration will result in treatment failure and potentially increased morbidity and mortality 1.