Treatment of Worsening Rash Suspected to be Cellulitis
For a worsening rash that could be cellulitis, start oral antibiotics active against streptococci immediately—cephalexin 500 mg four times daily or amoxicillin are first-line choices, with a 5-day course sufficient if clinical improvement occurs by day 5. 1
Initial Antibiotic Selection
The cornerstone of cellulitis treatment is antimicrobial therapy targeting streptococci, as these are the predominant causative organisms in non-purulent cellulitis. 2, 1
First-line oral antibiotics include: 2, 1
- Cephalexin 500 mg orally four times daily
- Amoxicillin
- Amoxicillin-clavulanate
- Dicloxacillin
- Penicillin
For penicillin-allergic patients: 1
- Clindamycin 300-450 mg orally four times daily
When to Add MRSA Coverage
Do NOT routinely cover MRSA for typical non-purulent cellulitis. 3 However, consider adding MRSA coverage if any of these risk factors are present: 1
- Penetrating trauma
- Evidence of MRSA infection elsewhere or nasal colonization
- Injection drug use
- Purulent drainage
- Systemic inflammatory response syndrome (SIRS)
- Athletes, prisoners, military recruits, or long-term care facility residents 4
For cellulitis with these risk factors, add: 1
- Trimethoprim-sulfamethoxazole OR doxycycline to a beta-lactam antibiotic
Treatment Duration
A 5-day course is as effective as 10 days if clinical improvement has occurred by day 5. 2, 1 This is a critical distinction that avoids unnecessary antibiotic exposure.
Extend treatment beyond 5 days only if: 1
- The infection has not improved within 5 days
- Systemic symptoms persist
Essential Adjunctive Measures
Beyond antibiotics, these interventions accelerate recovery: 1
- Elevate the affected area to promote gravity drainage of edema and inflammatory substances 1
- Treat predisposing conditions such as tinea pedis (athlete's foot), venous eczema, or trauma 1
- Examine interdigital toe spaces carefully in lower extremity cellulitis to identify and treat fissuring, scaling, or maceration that harbor pathogens 1
Monitoring for Treatment Response
Patients should show clinical improvement within 24-48 hours of starting appropriate antibiotics. 1
Failure to improve warrants consideration of: 4
- Resistant organisms (particularly MRSA)
- Misdiagnosis (pseudocellulitis mimickers like venous stasis dermatitis, contact dermatitis, or fixed drug eruption) 3, 5
- Deeper infection such as necrotizing fasciitis 6
Red Flags Requiring Hospitalization
Admit patients with: 1
- SIRS, altered mental status, or hemodynamic instability
- Concern for deeper or necrotizing infection (pain disproportionate to findings, violaceous bullae, skin sloughing, rapid progression, or gas in tissue) 6
- Severe immunocompromise
- Failed outpatient treatment
Common Pitfalls to Avoid
The term "cellulitis" should not be used for purulent collections (abscesses, furuncles, septic bursitis), as these require drainage as primary treatment, not antibiotics alone. 2 This distinction is clinically crucial and frequently misunderstood.
Blood cultures and tissue biopsies are unnecessary for typical cellulitis without systemic symptoms. 2, 6 Reserve these for patients with malignancy, severe systemic features, unusual predisposing factors, or immunocompromise. 2
Do not assume MRSA coverage is needed for all cellulitis in the era of community-acquired MRSA—the majority of non-purulent cellulitis remains streptococcal or methicillin-sensitive staph. 3