What is the initial treatment for a patient presenting with cellulitis?

Initial Treatment for Cellulitis

For patients presenting with uncomplicated cellulitis, the initial treatment should be oral cephalexin 500 mg 3-4 times daily for 5-6 days, targeting beta-hemolytic Streptococcus and methicillin-sensitive Staphylococcus aureus (MSSA). 1

First-Line Treatment Options

• Standard first-line therapy:
  • Cephalexin 500 mg orally 3-4 times daily for 5-6 days 1
  • Clindamycin 300-450 mg orally three times daily for 5-6 days (alternative) 1
  • Amoxicillin-clavulanate 875/125 mg orally twice daily for 5-6 days (alternative) 1

Treatment Algorithm Based on Clinical Presentation

Uncomplicated Cellulitis (No Abscess)

1. Start with cephalexin targeting beta-hemolytic Streptococcus and MSSA 1, 2
2. Evaluate for improvement within 48-72 hours
3. If no improvement after 72 hours, reassess diagnosis and consider changing antibiotic regimen 1

When to Consider MRSA Coverage

Add or switch to MRSA-active antibiotics (trimethoprim-sulfamethoxazole or clindamycin) if:

• Purulent cellulitis 1
• High local MRSA prevalence 3
• Patient has specific risk factors:
  • Athletes
  • Children
  • Men who have sex with men
  • Prisoners
  • Military recruits
  • Long-term care facility residents
  • Prior MRSA exposure
  • Intravenous drug users 2

Special Considerations

Severe Infections or Inpatient Management

For severe infections requiring hospitalization:

• Vancomycin 15 mg/kg IV every 12 hours 1
• Linezolid 600 mg IV/PO every 12 hours (alternative) 1
• Consider adding gram-negative coverage if risk factors present 1

Patient-Specific Factors

• Renal impairment: Adjust dose of cephalexin for creatinine clearance <30 mL/min 1
• Pediatric patients: Avoid doxycycline in children under 8 years 1
• Pregnancy: Avoid doxycycline; cephalexin is generally safe 1

Diagnostic Considerations

• Obtain blood cultures before starting antibiotics if systemic symptoms present 1
• Culture any wound drainage or abscess material if present 1
• Consider soft tissue ultrasound to rule out abscess 4

Evidence Considerations and Controversies

Research has shown mixed results regarding MRSA coverage for uncomplicated cellulitis:

• A 2010 study found trimethoprim-sulfamethoxazole had higher success rates than cephalexin (91% vs 74%) in areas with high MRSA prevalence 3

• However, more recent randomized controlled trials found no significant benefit to adding trimethoprim-sulfamethoxazole to cephalexin for uncomplicated cellulitis 5, 4

• The JAMA 2017 study showed that in the per-protocol analysis, clinical cure occurred in 83.5% with combination therapy versus 85.5% with cephalexin alone 4

Prevention of Recurrence

• Address predisposing factors:
  • Treat underlying skin conditions
  • Manage edema and venous insufficiency
  • Improve hygiene practices
  • Consider decolonization for recurrent MRSA infections 1

Follow-Up

• Patients should follow up within 2-3 days to ensure improvement 1
• If no improvement after 72 hours on oral therapy, reassess diagnosis and consider changing antibiotics 1