What is the recommended treatment for cellulitis of the foot?

Treatment of Foot Cellulitis

First-Line Antibiotic Therapy

For uncomplicated cellulitis of the foot, beta-lactam monotherapy with cephalexin 500 mg orally four times daily for 5 days is the recommended treatment, achieving a 96% success rate even in settings with high MRSA prevalence. 1, 2

Preferred Oral Regimens

• Cephalexin 500 mg orally four times daily is the first-line choice for typical nonpurulent foot cellulitis 2
• Dicloxacillin 250-500 mg orally every 6 hours provides excellent streptococcal and methicillin-sensitive S. aureus coverage 1, 3
• Penicillin V 250-500 mg orally four times daily is an alternative that effectively targets streptococci 2
• Amoxicillin is also appropriate as beta-lactam monotherapy 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 2 This represents a significant departure from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases 1.

When to Add MRSA Coverage

MRSA coverage is usually unnecessary for typical foot cellulitis, as MRSA is an uncommon cause even in high-prevalence settings 1, 2. However, add MRSA-active antibiotics when specific risk factors are present:

• Penetrating trauma with deep tissue involvement 1, 2
• Purulent drainage or exudate from the wound 1, 2
• Evidence of MRSA infection elsewhere or nasal MRSA colonization 2
• Systemic inflammatory response syndrome (SIRS) including fever, tachycardia, tachypnea, or abnormal WBC 2
• Injection drug use 1

MRSA-Active Regimens When Indicated

• Clindamycin 300-450 mg orally four times daily provides single-agent coverage for both streptococci and MRSA, avoiding the need for combination therapy 1, 2
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (doxycycline alone is inadequate due to unreliable streptococcal coverage) 1
• Trimethoprim-sulfamethoxazole PLUS a beta-lactam 1

Critical pitfall: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1.

Penicillin/Cephalosporin Allergy Options

• Clindamycin 300-450 mg orally four times daily is the optimal choice for patients allergic to both penicillins and cephalosporins, providing coverage for both streptococci and MRSA without requiring combination therapy 1, 2
• Use clindamycin only if local MRSA clindamycin resistance rates are <10% 1

Severe Infections Requiring Hospitalization

Admit patients with any of the following 2:

• SIRS criteria (fever, tachycardia, tachypnea, abnormal WBC)
• Altered mental status or hemodynamic instability
• Concern for deeper or necrotizing infection
• Severe immunocompromise
• Failure of outpatient treatment after 24-48 hours

Inpatient IV Regimens

For hospitalized patients with complicated foot cellulitis:

• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line (A-I evidence) 1
• Cefazolin 1-2 g IV every 8 hours is preferred for uncomplicated cellulitis without MRSA risk factors 1
• Alternative IV agents include linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV once daily, or clindamycin 600 mg IV three times daily (if local resistance <10%) 1

For severe cellulitis with systemic toxicity or suspected necrotizing fasciitis:

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours is the mandatory broad-spectrum combination 1
• Alternative combinations include vancomycin plus a carbapenem or vancomycin plus ceftriaxone and metronidazole 1

Essential Adjunctive Measures

• Elevate the affected foot above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances 1, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration; treating these eradicates pathogen colonization and reduces recurrence risk 1, 2
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, obesity, and eczema 1, 2

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors:

• Prophylactic antibiotics such as oral penicillin V 250 mg twice daily or erythromycin 250 mg twice daily may be considered 1, 2
• Continue prophylaxis as long as predisposing factors persist 1

Special Considerations for Diabetic Foot Infections

For moderate diabetic foot infections, broader coverage may be warranted:

• Amoxicillin-clavulanate (beta-lactam/beta-lactamase inhibitor combination) 1
• Second or third-generation cephalosporins (cefuroxime, cefotaxime, ceftriaxone) 1

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized or because MRSA prevalence is high in your institution; beta-lactam monotherapy succeeds in 96% of typical cases 1, 4
• Do not continue ineffective antibiotics beyond 48 hours; progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection 1
• Do not overlook necrotizing fasciitis warning signs: severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, systemic toxicity, or bullous changes require emergent surgical consultation 1
• Do not use combination therapy when monotherapy is appropriate, as this increases adverse effects without improving outcomes 1