What are the first-line antibiotics for uncomplicated cellulitis of the leg?

First-Line Antibiotics for Uncomplicated Cellulitis of the Leg

For uncomplicated cellulitis of the leg, first-line antibiotic therapy should include a cephalosporin (such as cephalexin), penicillin, or clindamycin for a duration of 5-6 days, targeting streptococci which are the most common causative pathogens. 1, 2

First-Line Antibiotic Options

• Cephalosporins (e.g., cephalexin) are recommended as first-line therapy for uncomplicated cellulitis due to their excellent coverage against streptococci, which are the most common causative pathogens 1, 3
• Penicillins (e.g., flucloxacillin) are equally effective first-line options for uncomplicated cellulitis 1
• Clindamycin (300-450 mg orally four times daily) is an excellent alternative, particularly for patients with penicillin or cephalosporin allergies 2

Duration of Therapy

• A 5-6 day course of antibiotics is as effective as a 10-day course for uncomplicated cellulitis if clinical improvement occurs within the first 5 days 1, 4
• The 2019 National Institute for Health and Care Excellence (NICE) guideline recommends a course of 5-7 days 1
• Treatment should be extended if the infection has not improved after 5 days 1, 2

Special Considerations for MRSA Coverage

• Standard first-line antibiotics (cephalosporins, penicillins) primarily target streptococci, which are the most common cause of uncomplicated cellulitis 1, 2
• Consider MRSA coverage only in specific circumstances:
  • Cellulitis associated with penetrating trauma 1, 2
  • Evidence of MRSA infection elsewhere 1, 2
  • Nasal colonization with MRSA 1
  • History of injection drug use 1, 2
  • Presence of systemic inflammatory response syndrome 1, 2
  • Presence of purulent drainage 2
  • In areas with high MRSA prevalence, trimethoprim-sulfamethoxazole or clindamycin may be preferred 5

Treatment Algorithm

1. For uncomplicated cellulitis without MRSA risk factors:

   • First choice: Cephalexin or other cephalosporin 1, 3
   • Alternative: Penicillin (e.g., flucloxacillin) 1
   • For penicillin/cephalosporin allergies: Clindamycin 2

2. For cellulitis with MRSA risk factors:

   • Add coverage effective against both MRSA and streptococci 1
   • Options include trimethoprim-sulfamethoxazole or clindamycin 2, 5

3. Duration of therapy:

   • Initial course: 5-6 days 1, 4
   • Reassess at 5 days 1
   • Extend therapy if inadequate improvement 1, 2

Monitoring and Follow-up

• Monitor for signs of clinical improvement, including reduction in erythema and swelling, decreased pain and tenderness, and resolution of systemic symptoms if present 2
• Consider hospitalization if there is concern for deeper or necrotizing infection, poor adherence to therapy, severely immunocompromised patient, or outpatient treatment is failing 2

Adjunctive Measures

• Elevation of the affected area to promote gravity drainage of edema and inflammatory substances 2
• Treatment of predisposing factors such as tinea pedis, venous insufficiency, or underlying cutaneous disorders 2

Prevention of Recurrence

• For patients with recurrent cellulitis (≥2 episodes), prophylactic antibiotics may be considered 6
• Low-dose penicillin (250 mg twice daily) has been shown to be effective in preventing recurrent cellulitis 6, 7
• Identify and treat predisposing conditions such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities 2, 7