What broad-spectrum antibiotic should I prescribe for cellulitis?

Broad-Spectrum Antibiotic Selection for Cellulitis

For uncomplicated cellulitis, cephalexin 500 mg orally four times daily is the recommended first-line empiric treatment, targeting streptococci which are the most common causative organisms. 1 Only add MRSA coverage when specific risk factors are present.

First-Line Treatment Options

For non-purulent cellulitis, the Infectious Diseases Society of America recommends beta-lactam antibiotics that target streptococci:

• First choice: Cephalexin 500 mg orally four times daily
• Alternatives:
  • Dicloxacillin 500 mg orally four times daily
  • Amoxicillin-clavulanate 875/125 mg orally twice daily

These options are effective against both streptococci and methicillin-susceptible S. aureus (MSSA), which cover the most common pathogens in typical cellulitis. 1, 2

When to Consider MRSA Coverage

Add MRSA coverage only when specific risk factors are present:

• Purulent drainage
• History of penetrating trauma
• Previous MRSA infection
• No improvement after 48-72 hours of beta-lactam therapy

In these cases, consider:

• Trimethoprim-sulfamethoxazole
• Clindamycin (reserve for penicillin-allergic patients or when other options are inappropriate) 3

Treatment Duration and Follow-up

• Standard treatment duration for uncomplicated cellulitis: 5-7 days 1
• Extend treatment if clinical improvement is not observed
• Reassess within 48-72 hours to evaluate treatment response
• Consider hospitalization if no improvement within 24-48 hours or signs of progressive infection 1

Special Considerations

Severe Cellulitis

For severe cellulitis with systemic inflammatory response syndrome (SIRS), altered mental status, hemodynamic instability, or signs of deeper infection, hospitalization for IV antibiotics is recommended. 1

Recurrent Cellulitis

For patients with 3-4 episodes per year, consider:

• Addressing predisposing conditions (edema, obesity, venous insufficiency, toe web abnormalities)
• Prophylactic antibiotics (oral penicillin or erythromycin twice daily, or monthly intramuscular benzathine penicillin injections) 1

Common Pitfalls to Avoid

1. Overuse of MRSA coverage: Despite rising rates of community-acquired MRSA, empiric coverage for non-purulent cellulitis is generally not recommended. 2

2. Misdiagnosis: Cellulitis can be confused with non-infectious mimickers such as venous stasis dermatitis, contact dermatitis, eczema, and lymphedema. Ensure proper diagnosis before initiating antibiotics. 2

3. Inadequate follow-up: Daily follow-up is essential until clear improvement is noted. 1

4. Failure to elevate the affected limb: Elevation promotes drainage of edema and inflammatory substances, which is a critical aspect of treatment. 1

In areas with high MRSA prevalence, research has shown that trimethoprim-sulfamethoxazole had higher success rates than cephalexin (91% vs 74%) 4, but current guidelines still recommend beta-lactams as first-line therapy for non-purulent cellulitis with MRSA coverage only when specific risk factors are present. 1, 2