What antibiotic is recommended for soft tissue infections?

Antibiotic Selection for Soft Tissue Infections

For uncomplicated cellulitis without systemic signs, use cephalexin 500 mg orally every 6 hours or an agent active against streptococci; for severe infections with systemic toxicity or suspected MRSA, use vancomycin plus piperacillin-tazobactam or a carbapenem. 1

Mild Infections (Outpatient, No Systemic Signs)

For typical cellulitis without systemic toxicity, target streptococci as the primary pathogen:

• Cephalexin 500 mg orally every 6 hours is the first-line oral agent 1, 2
• Alternative: Cefazolin 0.5-1 g IV every 8 hours if parenteral therapy needed 1
• Penicillin-allergic patients: Clindamycin 300 mg orally 3 times daily 1, 3

These recommendations apply to cellulitis without penetrating trauma, injection drug use, or known MRSA colonization 1. The infection should lack systemic inflammatory response syndrome (SIRS) criteria 1.

Moderate Infections (Systemic Signs Present)

When cellulitis is associated with fever, tachycardia, or other systemic signs, many clinicians include MSSA coverage:

• Oral options: Cephalexin 500 mg every 6 hours or dicloxacillin 500 mg 4 times daily 1
• IV options: Nafcillin or oxacillin 2 g every 6 hours, or cefazolin 1 g every 8 hours 1

Severe Infections (MRSA Risk or Systemic Toxicity)

For patients with penetrating trauma, injection drug use, MRSA colonization, or SIRS, empiric MRSA coverage is mandatory:

• Vancomycin 15 mg/kg IV every 12 hours is the cornerstone agent 1
• Add broad gram-negative and anaerobic coverage with:
  • Piperacillin-tazobactam 3.375-4.5 g IV every 6-8 hours, OR 1
  • Carbapenem (imipenem 1 g every 6-8 hours, meropenem 1 g every 8 hours, or ertapenem 1 g daily), OR 1
  • Ceftriaxone 1 g daily plus metronidazole 500 mg every 8 hours 1

Alternative to vancomycin: Linezolid 600 mg IV/PO every 12 hours 1

Necrotizing Soft Tissue Infections

Prompt surgical consultation is critical; empiric antibiotics must be broad-spectrum:

• Vancomycin or linezolid PLUS piperacillin-tazobactam or a carbapenem 1
• Alternative: Vancomycin plus ceftriaxone and metronidazole 1
• For documented Group A streptococcal necrotizing fasciitis: Penicillin 2-4 million units IV every 4-6 hours PLUS clindamycin 600-900 mg IV every 8 hours 1

Clindamycin suppresses toxin production and is superior to penicillin alone in animal models 1. Penicillin is added due to potential clindamycin resistance 1.

Pyomyositis

Vancomycin is recommended for initial empirical therapy:

• Vancomycin 15 mg/kg IV every 12 hours 1
• Add gram-negative coverage (e.g., ceftriaxone, fluoroquinolone) in immunocompromised patients or after open trauma 1
• For MSSA: Switch to cefazolin or nafcillin/oxacillin 1
• Duration: 2-3 weeks total, can transition to oral once clinically improved and bacteremia cleared 1

Bite Wounds (Animal or Human)

Amoxicillin-clavulanate 875/125 mg orally twice daily is the preferred single agent:

• Covers streptococci, staphylococci, anaerobes, and Pasteurella (animal) or Eikenella (human) 1
• IV alternative: Ampicillin-sulbactam 1.5-3 g every 6 hours 1
• Penicillin-allergic: Moxifloxacin 400 mg daily (covers anaerobes as monotherapy) 1

Common pitfall: First-generation cephalosporins miss Pasteurella and Eikenella; clindamycin misses Eikenella 1. Avoid these as monotherapy for bite wounds.

Surgical Site Infections

Incision and drainage is primary treatment; antibiotics are adjunctive:

• For trunk/extremity (away from axilla/perineum): Cephalexin 500 mg every 6 hours orally or cefazolin 0.5-1 g IV every 8 hours 1
• For axilla/perineum (anaerobic risk): Metronidazole 500 mg every 8 hours PLUS ciprofloxacin 400 mg IV every 12 hours or levofloxacin 750 mg daily 1
• For intestinal/GU surgery: Piperacillin-tazobactam 3.375 g every 6 hours or ertapenem 1 g daily 1

Systemic antibiotics are indicated only when erythema extends >5 cm from wound edge or systemic signs present 1

Duration of Therapy

• Uncomplicated cellulitis: 5-7 days (can extend to 10 days if slow response) 1
• Pyomyositis: 2-3 weeks 1
• Necrotizing infections: Continue until no further debridement needed, clinically improved, and afebrile for 48-72 hours 1
• Bite wounds with preemptive therapy: 3-5 days 1

Key Clinical Pitfalls

Do not use vancomycin alone for necrotizing infections—the polymicrobial nature requires gram-negative and anaerobic coverage 1.

Do not use first-generation cephalosporins for bite wounds—they miss critical pathogens like Pasteurella and anaerobes 1.

Do not delay surgical consultation for suspected necrotizing fasciitis—antibiotics are adjunctive to urgent surgical debridement 1.

Consider local MRSA prevalence—in areas with high community-acquired MRSA rates, empiric coverage may be warranted even for moderate cellulitis 1, 4.