What is the best antibiotic for treating leg cellulitis?

Best Antibiotic for Leg Cellulitis

For typical, non-purulent leg cellulitis, first-line treatment should be an antibiotic active against streptococci, such as penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin, or clindamycin. 1

First-Line Antibiotic Selection

• Cephalexin (500 mg four times daily) is an excellent first choice for typical cellulitis as it covers streptococci, which are the most common causative organisms 1, 2
• Penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, and clindamycin are also appropriate first-line options 1, 3
• MRSA is an unusual cause of typical cellulitis, and treatment specifically targeting this organism is usually unnecessary in uncomplicated cases 1, 4

Duration of Therapy

• A 5-day course of antibiotics is as effective as a 10-day course for uncomplicated cellulitis if clinical improvement has occurred by day 5 1
• Treatment should be extended if the infection has not improved after the initial 5-day period 1
• Recent guidelines from the American College of Physicians (2021) recommend a 5- to 6-day course of antibiotics for nonpurulent cellulitis 1

Special Considerations for MRSA Coverage

• Consider adding MRSA coverage only in specific situations:

  • Cellulitis associated with penetrating trauma, especially from illicit drug use 1, 3
  • Presence of purulent drainage 1, 2
  • Concurrent evidence of MRSA infection elsewhere 1, 3
  • History of MRSA colonization 1, 2
  • Systemic inflammatory response syndrome 1, 3

• Options for MRSA coverage include:

  • Clindamycin alone 1, 5
  • Combination of SMX-TMP or doxycycline with a β-lactam (e.g., penicillin, cephalexin, or amoxicillin) 1, 2
  • For severe infections requiring IV therapy: vancomycin, daptomycin, linezolid, or telavancin 1, 6

Adjunctive Measures

• Elevation of the affected area is crucial to promote gravity drainage of edema and inflammatory substances 1
• Identify and treat predisposing conditions such as:
  • Tinea pedis or other toe web abnormalities 1, 2
  • Venous insufficiency 1, 7
  • Prior trauma to the area 2, 7
• Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adult patients to reduce inflammation and hasten resolution 1, 2

Prevention of Recurrence

• For patients with frequent recurrences (3-4 episodes per year), consider prophylactic antibiotics 2, 8
• Options include:
  • Oral penicillin or erythromycin twice daily 1, 8
  • Intramuscular benzathine penicillin every 2-4 weeks 3, 8
• A randomized controlled trial showed that prophylactic low-dose penicillin (250 mg twice daily) reduced recurrence rates in patients with two or more previous episodes of cellulitis 8

Common Pitfalls to Avoid

• Don't routinely add MRSA coverage for typical non-purulent cellulitis without specific risk factors 1, 4
• Don't extend treatment unnecessarily beyond 5 days if clinical improvement has occurred 1, 2
• Don't forget to examine interdigital toe spaces in lower-extremity cellulitis, as treating fissuring or maceration may reduce recurrence 2, 7
• Don't overlook the importance of elevating the affected area, especially in patients with venous insufficiency or lymphedema 1