What is the preferred treatment between clindamycin and metronidazole for skin tissue infections?

Clindamycin vs Metronidazole for Skin and Soft Tissue Infections

Clindamycin is the preferred agent over metronidazole for most skin and soft tissue infections because it provides superior coverage against the primary pathogens—aerobic gram-positive cocci (including S. aureus and streptococci) and anaerobes—while metronidazole lacks reliable activity against gram-positive anaerobic cocci and has no aerobic coverage. 1

Microbiologic Coverage Differences

The fundamental distinction between these agents lies in their antimicrobial spectrum:

• Clindamycin provides coverage against anaerobes AND aerobic gram-positive cocci, including most S. aureus strains and streptococci 1
• Metronidazole has the greatest anaerobic spectrum against enteric gram-negative anaerobes, but is less effective against gram-positive anaerobic cocci and completely ineffective against aerobic pathogens 1, 2

This distinction is critical because S. aureus and streptococci remain the leading causes of skin and soft tissue infections 3, and metronidazole provides no coverage for these organisms 2.

Clinical Application by Infection Type

Necrotizing Fasciitis (Mixed Polymicrobial Infections)

For community-acquired mixed infections, the IDSA guidelines recommend:

• First-line regimen: Ampicillin-sulbactam PLUS clindamycin PLUS ciprofloxacin 1
• Alternative for penicillin allergy: Clindamycin OR metronidazole with an aminoglycoside or fluoroquinolone 1

The 2014 updated guidelines recommend broader empiric coverage including MRSA:

• Vancomycin, linezolid, or daptomycin PLUS piperacillin-tazobactam, a carbapenem, OR ceftriaxone plus metronidazole 1

Key point: When metronidazole is used in these regimens, it must be combined with agents covering aerobic gram-positive organisms because metronidazole alone is inadequate 1.

Streptococcal Necrotizing Fasciitis and Toxic Shock Syndrome

Clindamycin plus penicillin is the definitive treatment 1. The rationale for clindamycin is compelling:

• Suppresses streptococcal toxin production 1
• Modulates cytokine (TNF) production 1
• Demonstrated superior efficacy versus penicillin in animal studies 1
• Two observational studies showed greater efficacy for clindamycin than β-lactam antibiotics alone 1

Metronidazole has no role in this specific infection type 1.

Clostridial Gas Gangrene

Clindamycin plus penicillin is recommended for definitive treatment of clostridial myonecrosis 1. Experimental data demonstrate that clindamycin is more effective than penicillin for gas gangrene 1.

Simple Skin and Soft Tissue Infections

For non-necrotizing infections:

• Clindamycin is effective as monotherapy for purulent and non-purulent infections 1, 4, 3
• A comparative study showed clindamycin achieved cure in 27/31 patients versus 18/30 for cloxacillin by day 15, though differences were not statistically significant 4
• Metronidazole is not recommended as monotherapy due to lack of aerobic coverage 2

Important Caveats

Resistance Considerations

• Clindamycin resistance is emerging as a problem in some clinical settings, particularly with MRSA 3
• Macrolide resistance in group A streptococci varies geographically: <5% in the US, 8.2% in Germany, 18.3% in Spain 1
• Some macrolide-resistant strains also exhibit clindamycin resistance, though this is rare in the US (0.5% of group A streptococci) 1
• Testing for inducible clindamycin resistance (D-test) is essential when treating MRSA with clindamycin 1

When Metronidazole Is Appropriate

Metronidazole should be used in combination regimens when:

• Treating mixed infections with suspected Bacteroides fragilis or other enteric gram-negative anaerobes 1, 2
• Patient has severe penicillin hypersensitivity requiring alternative coverage 1
• Always combined with agents covering aerobic gram-positive organisms (aminoglycosides, fluoroquinolones, or vancomycin) 1

Practical Dosing

Clindamycin: 600-900 mg IV every 8 hours for adults; 10-13 mg/kg/dose every 8 hours for pediatrics 1

Metronidazole: 500 mg IV every 6 hours for adults; 7.5 mg/kg/dose every 6 hours for pediatrics 1

Bottom Line Algorithm

1. For any skin/soft tissue infection where S. aureus or streptococci are suspected: Choose clindamycin 1, 3
2. For necrotizing infections with mixed flora: Use clindamycin-based combination therapy 1
3. For streptococcal necrotizing fasciitis: Clindamycin plus penicillin (mandatory) 1
4. Only use metronidazole: In combination regimens for mixed infections when B. fragilis is a concern, never as monotherapy 1, 2