What is the recommended antibiotic for cellulitis of the foot?

Antibiotic Treatment for Cellulitis of the Foot

First-Line Treatment Recommendation

For uncomplicated cellulitis of the foot, use cephalexin 500 mg orally four times daily for 5 days if clinical improvement occurs—MRSA coverage is unnecessary in typical cases. 1, 2

Beta-lactam monotherapy is the standard of care for typical uncomplicated foot cellulitis, with a 96% success rate, confirming that MRSA coverage is usually unnecessary even in high-prevalence settings. 1

Treatment Algorithm by Clinical Presentation

Mild, Nonpurulent Cellulitis (No Complicating Features)

Oral beta-lactam monotherapy:

• Cephalexin 500 mg orally four times daily (preferred first-line) 1, 2
• Dicloxacillin 250-500 mg every 6 hours 1
• Amoxicillin (standard dosing) 1
• Penicillin V 250-500 mg four times daily 1

Duration: Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 3 Five-day courses are as effective as 10-day courses for uncomplicated cellulitis. 1

For Penicillin/Cephalosporin Allergy

Clindamycin 300-450 mg orally every 6 hours for 5 days provides single-agent coverage for both streptococci and MRSA without requiring combination therapy. 1, 2 This should only be used if local MRSA clindamycin resistance rates are <10%. 1

Alternative options include:

• Fluoroquinolones (levofloxacin, moxifloxacin) 4
• Trimethoprim-sulfamethoxazole 4
• Doxycycline 4

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1, 5
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

MRSA-active combination regimens:

• Trimethoprim-sulfamethoxazole 1-2 DS tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin) 1
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1
• Clindamycin 300-450 mg every 6 hours as monotherapy (covers both streptococci and MRSA) 1

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

Severe Cellulitis Requiring Hospitalization

Hospitalize if any of the following are present: 1

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 2
• Failure of outpatient treatment after 24-48 hours 1

IV antibiotic regimens for severe cellulitis:

For uncomplicated severe cellulitis without MRSA risk factors:

• Cefazolin 1-2 g IV every 8 hours (preferred) 1
• Oxacillin 2 g IV every 6 hours 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 1
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1

Duration: 7-14 days for complicated infections, guided by clinical response. 1

Special Considerations for Diabetic Foot Infections

For patients with diabetes and foot cellulitis, the IWGDF/IDSA guidelines recommend:

• Beta-lactam/beta-lactamase inhibitor combinations (amoxicillin-clavulanate, ampicillin-sulbactam) for moderate infections 4
• Consider broader coverage with second or third-generation cephalosporins (cefuroxime, cefotaxime, ceftriaxone) 4
• Treatment duration may extend beyond 5 days in diabetic patients compared to non-diabetic patients 1
• Avoid systemic corticosteroids in diabetic patients despite evidence showing benefit in non-diabetic adults 1

Essential Adjunctive Measures

Elevation of the affected foot is critical and often neglected—it hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2

Treat predisposing conditions: 1, 2

• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration 1
• Address venous insufficiency, lymphedema, and chronic edema 1
• Treat toe web abnormalities to reduce recurrence risk 1

Monitoring and Treatment Failure

Reassess within 24-48 hours to verify clinical response. 1 If no improvement with appropriate first-line antibiotics, consider:

• Resistant organisms (add MRSA coverage) 1
• Abscess requiring drainage 1
• Deep vein thrombosis mimicking cellulitis 1
• Necrotizing infection requiring surgical consultation 1

Warning signs of necrotizing fasciitis requiring emergent surgical consultation: 1

• Severe pain out of proportion to examination 1
• Skin anesthesia 1
• Rapid progression 1
• Gas in tissue 1
• Bullous changes 1

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics:

• Oral penicillin V 1 g twice daily 1
• Oral erythromycin 250 mg twice daily 1
• Duration: 4-52 weeks or intramuscular benzathine penicillin every 2-4 weeks 1

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical foot cellulitis without specific risk factors—MRSA is an uncommon cause even in high-prevalence settings. 1
• Do not extend treatment beyond 5 days automatically—extend only if clinical improvement has not occurred. 1
• Do not use combination therapy when monotherapy is appropriate—this increases adverse effects without improving outcomes. 1
• Do not delay surgical consultation if any signs of necrotizing infection are present—these infections progress rapidly and require debridement. 1