What antibiotics are recommended for skin and soft tissue infections?

Antibiotic Selection for Skin and Soft Tissue Infections

The choice of antibiotic for skin and soft tissue infections depends primarily on infection severity and whether the infection is purulent or non-purulent, with mild non-purulent infections requiring only streptococcal coverage while severe or purulent infections require MRSA coverage. 1

Mild Non-Purulent Infections (Cellulitis without systemic signs)

For typical cellulitis without systemic signs of infection, use an antimicrobial agent active against streptococci 1:

Oral options:

• Cephalexin 500 mg every 6 hours 1, 2
• Dicloxacillin 500 mg four times daily 1
• Penicillin VK 250-500 mg every 6 hours 1
• Clindamycin 300-450 mg three times daily (if penicillin allergic) 1

Duration: 5 days minimum, extended if not improved 1

Moderate Non-Purulent Infections (Cellulitis with systemic signs)

When systemic signs are present (fever, tachycardia), many clinicians include coverage against methicillin-susceptible S. aureus (MSSA) 1:

Oral options:

• Cephalexin 500 mg every 6 hours 1, 2
• Dicloxacillin 500 mg four times daily 1

Severe Non-Purulent Infections (SIRS, penetrating trauma, MRSA risk factors)

For patients with penetrating trauma, evidence of MRSA elsewhere, nasal MRSA colonization, injection drug use, or systemic inflammatory response syndrome (SIRS), use agents effective against both MRSA and streptococci 1:

Intravenous options:

• Vancomycin 15 mg/kg every 12 hours 1
• Linezolid 600 mg every 12 hours IV or oral 1

For severely compromised patients, use broad-spectrum coverage:

• Vancomycin plus piperacillin-tazobactam 3.375-4.5 g every 6-8 hours 1, 3
• Vancomycin plus imipenem/meropenem 1 g every 8 hours 1

Purulent Infections (Abscesses)

Incision and drainage is the primary treatment 1. For simple abscesses with minimal systemic signs (temperature <38.5°C, WBC <12,000, pulse <100), antibiotics are unnecessary after drainage 1, 4.

Antibiotics are indicated when:

• Temperature >38.5°C or heart rate >110 beats/minute 1
• Erythema extending >5 cm beyond wound margins 1
• Multiple lesions or immunocompromised state 1

Oral MRSA-active options:

• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily 1
• Doxycycline 100 mg twice daily 1
• Clindamycin 300-450 mg three times daily 1

Necrotizing Infections

Prompt surgical consultation is mandatory 1. Empiric treatment must be broad-spectrum as etiology can be polymicrobial or monomicrobial 1:

Initial empiric regimens:

• Vancomycin or linezolid PLUS piperacillin-tazobactam 1
• Vancomycin PLUS a carbapenem (imipenem/meropenem) 1
• Vancomycin PLUS ceftriaxone 1 g every 24 hours AND metronidazole 500 mg every 8 hours 1

For documented Group A Streptococcal necrotizing fasciitis:

• Penicillin 2-4 million units every 4-6 hours IV PLUS clindamycin 600-900 mg every 6-8 hours IV 1

Bite Wounds (Animal or Human)

Preemptive antimicrobial therapy for 3-5 days is recommended for immunocompromised patients, asplenic patients, those with advanced liver disease, or moderate to severe injuries 1.

First-line oral option:

• Amoxicillin-clavulanate 875/125 mg twice daily 1

Intravenous options:

• Ampicillin-sulbactam 1.5-3.0 g every 6 hours 1
• Piperacillin-tazobactam 3.375 g every 6-8 hours 1

Common Pitfalls

• Do not use first-generation cephalosporins or penicillins alone for animal bites - they miss Pasteurella multocida and anaerobes 1
• Do not use fluoroquinolones or clindamycin alone for animal bites - fluoroquinolones miss MRSA and some anaerobes; clindamycin misses Pasteurella 1
• Treat predisposing conditions such as interdigital toe space maceration in lower extremity cellulitis to prevent recurrence 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults with cellulitis 1
• Hospitalize patients with SIRS, altered mental status, hemodynamic instability, concern for deeper/necrotizing infection, or failed outpatient therapy 1