What is the first-line antibiotic treatment for uncomplicated leg cellulitis?

First-Line Antibiotic Treatment for Uncomplicated Leg Cellulitis

For uncomplicated leg cellulitis, a cephalosporin (such as cephalexin), penicillin, or clindamycin is recommended as first-line therapy for 5 days, targeting primarily streptococci and methicillin-sensitive Staphylococcus aureus. 1

First-Line Antibiotic Options

• Cephalexin 500 mg orally four times daily for 5 days 1
• Penicillin or amoxicillin for streptococcal coverage 1, 2
• Dicloxacillin for staphylococcal coverage 1
• Clindamycin 300-450 mg orally four times daily for 5 days (especially for penicillin-allergic patients) 1, 3

Treatment Duration

• A 5-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
• Consider extending treatment if the infection has not improved after 5 days 1
• The 2019 NICE guideline recommends a course of 5-7 days 1

MRSA Considerations

• MRSA is an unusual cause of typical cellulitis 1
• Standard beta-lactam therapy (like cephalexin) is successful in 96% of typical cellulitis cases 1
• Consider MRSA coverage only in specific situations:
  • Cellulitis associated with penetrating trauma 1
  • Evidence of MRSA infection elsewhere 1, 3
  • Nasal colonization with MRSA 1
  • Injection drug use 1
  • Systemic inflammatory response syndrome 1
  • Purulent drainage 1, 3

MRSA Coverage Options (when indicated)

• Oral options: Trimethoprim-sulfamethoxazole, doxycycline, or clindamycin 1, 3
• If both streptococcal and MRSA coverage needed: Clindamycin alone or combination of trimethoprim-sulfamethoxazole or doxycycline with a beta-lactam 1
• Intravenous options for severe infections: Vancomycin, daptomycin, linezolid, or telavancin 1, 3

Adjunctive Measures

• Elevation of the affected area to promote drainage of edema and inflammatory substances 1, 3
• Treatment of underlying conditions that may predispose to infection:
  • Tinea pedis 1, 3
  • Venous eczema/stasis dermatitis 1, 3
  • Lymphedema 1, 5

Prevention of Recurrence

• Keep skin well hydrated with emollients 1
• Reduce underlying edema through elevation, compression stockings, or diuretic therapy if appropriate 1
• For frequent infections despite preventive measures, prophylactic antibiotics may be considered:
  • Monthly intramuscular benzathine penicillin injections of 1.2 MU 1
  • Oral therapy with twice-daily doses of either 250 mg of erythromycin or 1 g of penicillin V 1, 3

Clinical Pearls and Pitfalls

• Cellulitis is primarily a clinical diagnosis - cultures of blood, tissue aspirates, or skin biopsies are unnecessary for typical cases 1, 6
• Blood cultures should be obtained for patients with malignancy, severe systemic features, or unusual predisposing factors 1
• Inflammation may worsen after initiating therapy due to pathogen destruction releasing enzymes that increase local inflammation 1
• Distinguish cellulitis (which requires antibiotics) from purulent collections (which primarily require drainage) 1, 2
• A recent trial showed no significant benefit of adding trimethoprim-sulfamethoxazole to cephalexin for uncomplicated cellulitis 7