What is the first line treatment for cellulitis?

First Line Treatment for Cellulitis

The first line treatment for uncomplicated cellulitis is cephalexin 500mg 3-4 times daily for 5-6 days. 1

Treatment Algorithm for Cellulitis

Non-purulent Cellulitis (Most Common)

1. First-line therapy:

   • Cephalexin 500mg 3-4 times daily for 5-6 days 1
   • Alternative: Clindamycin 300-450mg three times daily for 5-6 days (especially for penicillin-allergic patients) 1
   • Alternative: Amoxicillin-clavulanate 875/125mg twice daily for 5-6 days 1

2. For MRSA consideration:

   • In areas with high MRSA prevalence or patients with risk factors (athletes, children, prisoners, prior MRSA exposure, IV drug users), consider MRSA coverage 2
   • Options include TMP-SMX, doxycycline, or clindamycin 1

Purulent Cellulitis

1. Primary treatment: Incision and drainage 1
2. Antibiotic therapy if systemic symptoms present:
   • TMP-SMX, doxycycline, or clindamycin 1

Severe Cellulitis Requiring IV Therapy

• Vancomycin IV, linezolid, daptomycin, or ceftaroline 1

Evidence Analysis

The World Health Organization and American College of Physicians recommend beta-lactam antibiotics like cephalexin as first-line treatment for uncomplicated cellulitis 1. This recommendation is based on the understanding that most cases of non-purulent cellulitis are caused by beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus (MSSA) 2, 3.

Despite the rise in community-acquired MRSA infections, multiple studies have shown that additional MRSA coverage is generally not necessary for typical non-purulent cellulitis. A 2017 randomized clinical trial found that adding TMP-SMX to cephalexin did not significantly improve clinical cure rates in the per-protocol analysis compared to cephalexin alone (83.5% vs 85.5%) 4.

Important Clinical Considerations

• Duration of therapy: Standard duration is 5-6 days for most skin infections 1
• Expected response: Clinical improvement should be seen within 72 hours; if not, reevaluate treatment plan 1
• Supportive care: Apply warm compresses 3-4 times daily, elevate affected area to reduce edema 1

Common Pitfalls and Caveats

1. Overtreatment for MRSA: Despite rising MRSA rates, evidence does not support routine MRSA coverage for typical non-purulent cellulitis 3. Reserve MRSA-active agents for:

   • Purulent infections
   • Known MRSA colonization
   • Failed first-line therapy
   • High-risk populations 1, 2

2. Misdiagnosis: Cellulitis is often misdiagnosed. Consider non-infectious mimics like:

   • Venous stasis dermatitis
   • Contact dermatitis
   • Lymphedema 3

3. Abscess evaluation: Always evaluate for underlying abscess, which would require drainage as primary treatment 1

4. Recurrent cellulitis: Address predisposing factors like:

   • Tinea pedis
   • Edema
   • Venous insufficiency
   • Obesity 1, 2

The evidence strongly supports cephalexin as first-line therapy for typical cellulitis, with consideration for alternative agents based on patient-specific factors such as allergies or local resistance patterns.