What is the recommended treatment for cellulitis?

Treatment of Cellulitis

For uncomplicated cellulitis, the recommended first-line treatment is oral antibiotics such as dicloxacillin (500 mg 4 times daily) or cephalexin (500 mg 4 times daily) for 5-6 days to target β-hemolytic Streptococcus and methicillin-sensitive Staphylococcus aureus. 1

Antibiotic Selection Algorithm

Outpatient Treatment (Mild to Moderate Cellulitis)

• First-line options:

  • Cephalexin: 500 mg orally 3-4 times daily for 5-6 days 1
  • Dicloxacillin: 500 mg orally 4 times daily for 5-6 days 1

• For penicillin-allergic patients:

  • Clindamycin: 300-450 mg orally 3 times daily for 5-6 days 1

• If MRSA is suspected (based on risk factors such as athletes, prisoners, prior MRSA exposure, IV drug users):

  • Doxycycline, TMP-SMX, or clindamycin 1, 2

Inpatient Treatment (Severe Cellulitis)

• Standard therapy:
  • Vancomycin: 15 mg/kg IV every 12 hours 1
  • Linezolid: 600 mg IV/PO every 12 hours 1

Treatment Duration and Monitoring

• Standard duration: 5-6 days for uncomplicated cellulitis 1
• Extend treatment if symptoms have not improved after initial course
• Reassess diagnosis if no improvement after 72 hours of appropriate therapy 1
• Follow-up within 2-3 days of starting treatment to ensure improvement 1

Special Populations

Pediatric Patients

• Avoid doxycycline in children under 8 years due to risk of dental staining 1
• Adjust dosing based on weight

Pregnant Patients

• Avoid doxycycline 1
• Cephalexin or clindamycin are generally safe options

Evidence Considerations

Recent high-quality evidence from the Infectious Diseases Society of America supports that most non-purulent cellulitis cases are caused by β-hemolytic streptococci or methicillin-sensitive S. aureus 1, 3. Despite rising rates of community-acquired MRSA, coverage for non-purulent cellulitis is generally not recommended unless specific risk factors are present 3.

A 2017 randomized clinical trial found that adding trimethoprim-sulfamethoxazole (which covers MRSA) to cephalexin did not significantly improve outcomes in uncomplicated cellulitis compared to cephalexin alone in the per-protocol analysis 4. This supports the guideline recommendation to focus on streptococcal and methicillin-sensitive S. aureus coverage for most cases.

Diagnostic Considerations

• Cellulitis is primarily a clinical diagnosis based on:
  • Expanding erythema
  • Warmth
  • Tenderness
  • Swelling 2
• Consider obtaining cultures from:
  • Any wound drainage or abscess material
  • Blood cultures if systemic symptoms are present 1

Common Pitfalls and Caveats

1. Misdiagnosis: Many conditions mimic cellulitis, including venous stasis dermatitis, contact dermatitis, and lymphedema 3. If treatment is failing, reconsider the diagnosis.

2. Overtreatment for MRSA: Despite concerns about MRSA, evidence shows that adding MRSA coverage for uncomplicated cellulitis does not improve outcomes 5, 4.

3. Inadequate Duration: While 5-6 days is sufficient for most cases, treatment should be extended if symptoms have not adequately improved 1.

4. Neglecting Predisposing Factors: Addressing underlying conditions (lymphedema, skin disorders, etc.) is crucial for preventing recurrence 1, 2.

5. Failure to Recognize Treatment Failure: If no improvement after 72 hours, reassess diagnosis and consider changing antibiotics 1.