What is the best antibiotic to prevent skin infection from a wound?

Best Antibiotic for Wound Infection Prophylaxis

Amoxicillin-clavulanate is the first-line antibiotic for preventing skin infections from wounds, particularly for high-risk injuries including deep wounds, bites, or significantly contaminated wounds, administered for 3-5 days. 1

When Antibiotic Prophylaxis is Actually Indicated

Antibiotic prophylaxis is not universally recommended for all wounds. 1 Reserve antibiotics for high-risk situations only:

• Deep or severe wounds with significant tissue damage 1
• Human or animal bites (30-50% of cat bites, 5-25% of dog bites, 20-25% of human bites become infected) 2
• Wounds near joints or periosteum 1
• Immunocompromised patients or those with severe comorbidities 2
• Severe cellulitis or significant contamination 2, 1
• Wounds with soil contamination and areas of ischemia 2

For simple, clean wounds presenting early with good perfusion, irrigation and debridement alone are sufficient—antibiotics add unnecessary risk without benefit. 2, 1

Recommended Antibiotic Regimen

First-Line Choice

Amoxicillin-clavulanate provides optimal coverage against the polymicrobial flora typically contaminating wounds: 1

• Staphylococcus aureus (most common pathogen)
• Streptococcus species
• Anaerobes
• Pasteurella species (animal bites)
• Eikenella corrodens (human bites)

Alternative for penicillin allergy: 2

• Fluoroquinolone (ciprofloxacin or levofloxacin) plus metronidazole, OR
• Moxifloxacin as monotherapy (covers anaerobes)

Duration

• 3 days for less severe wounds 1
• 5 days for more severe wounds with significant contamination 1
• Never extend beyond 5 days without documented infection 1

Critical Timing Considerations

Antibiotics must be initiated within 24 hours of injury for prophylactic benefit. 1 After 24 hours without clinical infection signs, prophylactic antibiotics are ineffective and should not be given. 1 This represents a common error—do not prescribe prophylactic antibiotics for wounds presenting late without infection.

Wound-Specific Considerations

Animal Bites

Amoxicillin-clavulanate or ampicillin-sulbactam covers Pasteurella multocida (present in 50% of dog bites, 75% of cat bites) plus oral anaerobes. 2 Cat bites have the highest infection risk and warrant prophylaxis. 2

Human Bites

These require coverage for Eikenella corrodens (resistant to first-generation cephalosporins, clindamycin, and macrolides), Streptococcus species (50%), S. aureus (40%), and anaerobes. 2 Amoxicillin-clavulanate remains first-line. 2 Consider post-exposure prophylaxis for HBV, HCV, and HIV. 2

Surgical/Clean Wounds

For clean surgical wounds or minor lacerations without the high-risk features above, prophylactic antibiotics are not indicated. 2 If surgical site infection develops with <5 cm erythema, temperature <38.5°C, and WBC <12,000, opening the wound without antibiotics is sufficient. 2

Contaminated/Dirty Wounds

For wounds contaminated with soil or fecal material, add penicillin to the regimen for Clostridium species coverage. 2 However, a second-generation cephalosporin with anaerobic coverage (cefoxitin) may be considered, though evidence suggests cefazolin (without anaerobic coverage) performs similarly in preventing infection. 3

When MRSA Coverage is Needed

Add vancomycin, linezolid, or daptomycin when: 2

• Penetrating trauma with purulent drainage
• Known MRSA colonization
• Injection drug use
• Systemic signs of infection (SIRS criteria)
• Failed initial therapy

Important caveat: For simple wound prophylaxis in immunocompetent patients, routine MRSA coverage is unnecessary. 2 Reserve broader coverage for established infections, not prophylaxis.

Essential Non-Antibiotic Management

Irrigation and surgical debridement are more important than antibiotics in preventing infection. 2, 1 This cannot be overemphasized:

• Deep irrigation of the wound (avoid excessive pressure that drives bacteria deeper) 1
• Debridement of all necrotic tissue 2, 1
• Delayed primary closure for most bite wounds (except facial wounds, which may be closed after copious irrigation and with preemptive antibiotics) 2

Common Pitfalls to Avoid

1. Do not use universal prophylaxis for all wounds—this drives resistance without benefit 1
2. Do not prescribe antibiotics >24 hours post-injury without infection signs 1
3. Do not extend prophylaxis beyond 5 days without documented infection 1
4. Do not use first-generation cephalosporins alone for bite wounds (misses Eikenella, Pasteurella, and anaerobes) 2
5. Do not rely on antibiotics alone—inadequate debridement is the primary cause of prophylaxis failure 2, 1

Tetanus Prophylaxis

Administer tetanus toxoid if >10 years since last dose for clean wounds, or >5 years for dirty wounds. 2 Tdap is preferred over Td if not previously given. 2