What is the first line treatment for cellulitis?

First-Line Treatment for Cellulitis

For typical non-purulent cellulitis, first-line treatment should be an oral antibiotic active against streptococci, such as cephalexin 500 mg four times daily, penicillin, amoxicillin, or clindamycin 300-450 mg four times daily (if penicillin-allergic), for 5 days if clinical improvement occurs. 1, 2

Antibiotic Selection Based on Clinical Presentation

Standard Non-Purulent Cellulitis

• Beta-lactam antibiotics targeting streptococci are the cornerstone of therapy, as most cellulitis arises from streptococcal species (often group A, B, C, or G), with the source frequently being macerated interdigital toe spaces harboring these organisms 1, 2, 3
• Recommended oral agents include:
  • Cephalexin 500 mg orally four times daily 2
  • Dicloxacillin 1, 2
  • Amoxicillin or amoxicillin-clavulanate 2
  • Penicillin 2
• For penicillin-allergic patients: Clindamycin 300-450 mg orally four times daily 1, 2

When to Add MRSA Coverage

• Consider adding MRSA-active therapy (trimethoprim-sulfamethoxazole or doxycycline) when cellulitis is associated with: 2, 4
  • Penetrating trauma or bug bites 2, 4
  • Purulent drainage 2
  • Evidence of MRSA infection elsewhere or nasal colonization 2
  • Injection drug use 2
  • Systemic inflammatory response syndrome (SIRS) 2
• Combination therapy options: Beta-lactam (amoxicillin or cephalexin) plus either trimethoprim-sulfamethoxazole or doxycycline provides coverage for both streptococci and CA-MRSA 2, 4
• In high MRSA-prevalence areas, trimethoprim-sulfamethoxazole demonstrated significantly higher treatment success (91%) compared to cephalexin alone (74%) 5

Route of Administration

Oral vs. Intravenous Therapy

• Most patients can receive oral antibiotics from the start, as oral therapy is as effective as intravenous therapy for uncomplicated cellulitis and requires fewer visits and less time in the emergency department 1, 6, 7
• Reserve parenteral therapy for:
  • Severely ill patients 1
  • Those unable to tolerate oral medications 1
  • Patients with SIRS, altered mental status, or hemodynamic instability 2
  • Concern for deeper or necrotizing infection 2
• Parenteral options include: Nafcillin, cefazolin, or vancomycin (for life-threatening penicillin allergies) 1

Duration of Treatment

• A 5-day course is as effective as 10 days if clinical improvement has occurred by day 5 1, 2, 6
• Extend treatment beyond 5 days only if the infection has not improved 2
• For uncomplicated cellulitis, the total duration should be 5-10 days based on clinical response 4

Adjunctive Measures

Essential Supportive Care

• Elevate the affected area to promote gravity drainage of edema and inflammatory substances 2, 4
• Examine and treat interdigital toe spaces for fissuring, scaling, or maceration that may harbor streptococci, particularly in lower extremity cellulitis 1, 2
• Address predisposing conditions such as tinea pedis, venous eczema, or trauma 2

Anti-Inflammatory Therapy

• Systemic corticosteroids may be considered in non-diabetic adults to reduce inflammation and hasten resolution, though this is based on limited evidence from a single trial showing benefit with an 8-day tapering course starting with prednisolone 30 mg 1, 2
• Preliminary data suggest that adding oral NSAIDs (ibuprofen 400 mg every 6 hours for 5 days) to antibiotic therapy may accelerate resolution, with 82.8% showing regression within 1-2 days versus 9.1% with antibiotics alone 8

Monitoring and Follow-Up

• Patients should show clinical improvement within 24-48 hours of starting appropriate antibiotics 2
• Hospitalization is indicated if:
  • Outpatient treatment is failing 2
  • There is concern for deeper or necrotizing infection 2
  • Severe immunocompromise is present 2
  • Poor adherence to therapy is anticipated 2

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical non-purulent cellulitis without risk factors, as S. aureus rarely causes cellulitis unless associated with underlying abscess or penetrating trauma 1
• Avoid unnecessary blood cultures in typical cases; reserve them for patients with malignancy, severe systemic features, unusual predisposing factors, or immunocompromise 2
• Do not overlook toe web examination in lower extremity cellulitis, as untreated interdigital maceration is a common source of recurrent streptococcal cellulitis 1, 2
• Recognize that cutaneous inflammation may worsen initially after starting antibiotics due to sudden pathogen destruction releasing inflammatory enzymes—this does not indicate treatment failure 1