First-Line Treatment for Cellulitis
For an adult patient with no significant medical history or allergies presenting with uncomplicated cellulitis, beta-lactam monotherapy is the standard of care, with cephalexin 500 mg orally every 6 hours for 5 days as the preferred first-line agent. 1
Antibiotic Selection
Cephalexin 500 mg orally four times daily (every 6 hours) is the preferred oral beta-lactam, providing excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, which are the primary pathogens in typical cellulitis 1, 2
Alternative oral beta-lactam options include dicloxacillin 250-500 mg every 6 hours, amoxicillin, or penicillin V 250-500 mg four times daily 1, 3
Beta-lactam monotherapy is successful in 96% of patients with typical uncomplicated cellulitis, confirming that MRSA coverage is usually unnecessary 1, 4
MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, and MRSA coverage should NOT be added reflexively 1, 5
Treatment Duration
Treat for exactly 5 days if clinical improvement occurs (defined as resolution of warmth and tenderness, improving erythema, and absence of fever) 1, 3
Extend treatment beyond 5 days ONLY if symptoms have not improved within this timeframe 1, 3
Traditional 7-14 day courses are no longer necessary for uncomplicated cases, as supported by high-quality randomized controlled trial evidence 1
When to Add MRSA Coverage
Add MRSA-active antibiotics ONLY when specific risk factors are present 1, 3:
- Penetrating trauma or injection drug use 1, 3
- Purulent drainage or exudate 1, 3
- Evidence of MRSA infection elsewhere or nasal MRSA colonization 1, 3
- Systemic inflammatory response syndrome (SIRS) 1
If MRSA coverage is needed, use clindamycin 300-450 mg orally every 6 hours (provides single-agent coverage for both streptococci and MRSA, avoiding need for combination therapy), but only if local MRSA clindamycin resistance rates are <10% 1
Essential Adjunctive Measures
Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances, which hastens clinical improvement 1, 3
Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration, and treat these conditions to eradicate colonization and reduce recurrent infection 1, 3
Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and eczema 1, 3
When to Hospitalize
Hospitalize if any of the following are present 1:
- Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
- Hypotension or hemodynamic instability 1
- Altered mental status or confusion 1
- Severe immunocompromise or neutropenia 1
- Concern for deeper or necrotizing infection 1
Critical Pitfalls to Avoid
Do not routinely add MRSA coverage for typical cellulitis without specific risk factors, as this represents overtreatment and increases antibiotic resistance 1
Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1, 6
Do not extend treatment to 10-14 days based on tradition or residual erythema alone, as some inflammation persists even after bacterial eradication 1
Reassess patients within 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens 1
Adjunctive Anti-Inflammatory Therapy
Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited (weak recommendation, moderate evidence) 1
Oral NSAIDs (ibuprofen 400 mg every 6 hours for 5 days) as adjunct therapy may lead to improved early clinical response at day 3, although this benefit is not sustained beyond 4 days 7, 8