What is the recommended treatment for cellulitis?

Recommended Treatment for Cellulitis

For mild to moderate cellulitis without MRSA risk factors, first-line treatment is cephalexin 500 mg orally 3-4 times daily or amoxicillin-clavulanate 875/125 mg twice daily for 5 days. 1

Treatment Algorithm Based on Severity

Mild to Moderate Cellulitis (Outpatient)

• First-line options (without MRSA risk factors):

  • Cephalexin 500 mg orally 3-4 times daily for 5 days 1
  • Amoxicillin-clavulanate 875/125 mg twice daily for 5 days 1

• For patients with beta-lactam allergies:

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

• When MRSA is suspected (based on risk factors such as athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, prior MRSA exposure, or IV drug users 2):

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

Moderate to Severe Cellulitis (Inpatient)

• First-line parenteral options:

  • Cefazolin 1-2 g IV every 8 hours 1
  • Oxacillin or nafcillin 2 g IV every 6 hours 1

• For beta-lactam allergic patients or suspected MRSA:

  • Vancomycin 15-20 mg/kg IV every 8-12 hours 1
  • For settings with high vancomycin MIC values >2 μg/mL: daptomycin 4 mg/kg IV daily 1

Duration and Monitoring

• Standard treatment duration is 5 days 1
• Extend treatment if infection has not improved within this period 1
• Monitor for improvement within 72 hours of starting treatment 1
• If no response after 72 hours, consider:
  • Reevaluation of diagnosis
  • Drainage procedure if not already performed
  • Change in antibiotic therapy 1

Supportive Care

• Elevation of the affected limb (strongly recommended) 1
• Incision and drainage for any purulent collections 1
• Regular wound cleaning and care 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic patients to speed resolution 1, 3

Important Clinical Considerations

Microbiology

Most cases of cellulitis (approximately 85%) are nonculturable, making the causative bacteria unknown 2. When organisms are identified, the majority are due to β-hemolytic Streptococcus and Staphylococcus aureus 2. This supports the first-line treatment recommendations targeting these organisms.

Diagnostic Challenges

Cellulitis is a clinical diagnosis based on history and physical examination, with no gold standard diagnostic test 4. Common mimickers include venous stasis dermatitis, contact dermatitis, eczema, lymphedema, and erythema migrans 4. If initial treatment fails, consider these alternative diagnoses.

MRSA Considerations

Despite rising rates of community-acquired MRSA, coverage for non-purulent cellulitis is generally not recommended unless specific risk factors are present 4. This aligns with the guideline recommendation to start with beta-lactam antibiotics for uncomplicated cases.

Prevention of Recurrence

• Address predisposing factors:
  • Treat tinea pedis and other causes of toe web abnormalities
  • Manage edema, obesity, and venous insufficiency
  • Consider prophylactic antibiotics for patients with frequent episodes 1
  • Restrict dietary sodium (<2.0 g/day) to reduce edema 1

Treatment Failures

If a patient fails to respond to standard therapy, consider:

1. Less common pathogens (e.g., Proteus mirabilis in patients with vascular disease) 5
2. Obtaining cultures when possible to guide targeted therapy
3. Extending treatment duration
4. Reassessing the diagnosis for potential mimickers of cellulitis

The evidence strongly supports a 5-day course of antibiotics targeting streptococci and staphylococci for most cases of cellulitis, with appropriate adjustments based on severity, suspected pathogens, and clinical response.