What is the recommended treatment for a patient with mild cellulitis?

Treatment of Mild Cellulitis

For mild, nonpurulent cellulitis, use beta-lactam monotherapy with oral antibiotics such as cephalexin 500 mg every 6 hours, dicloxacillin 250-500 mg every 6 hours, or amoxicillin for exactly 5 days if clinical improvement occurs—MRSA coverage is unnecessary and represents overtreatment in typical cases. 1, 2

First-Line Antibiotic Selection

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, confirming that MRSA coverage is usually unnecessary. 1 The Infectious Diseases Society of America specifically recommends the following oral agents for mild cellulitis:

• Cephalexin 500 mg orally every 6 hours (four times daily) 1, 2
• Dicloxacillin 250 mg every 6 hours for moderate infections (125 mg every 6 hours for very mild cases) 1, 3
• Amoxicillin (standard dosing) 1, 2
• Penicillin V 250-500 mg orally four times daily 1, 2
• Clindamycin 300-450 mg every 6 hours (if beta-lactam allergy or local MRSA resistance <10%) 1, 2

These agents provide excellent coverage against the primary pathogens: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, which account for the majority of cellulitis cases when organisms are identified. 4, 5

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred—extending treatment beyond this is unnecessary and increases antibiotic resistance without improving outcomes. 1, 2 Extension beyond 5 days is only indicated if symptoms have not improved within this timeframe. 1, 2 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

Clinical Algorithm for Duration Decision:

• If warmth and tenderness have resolved, erythema is improving, and patient is afebrile: Stop antibiotics after 5 days 1
• If no improvement in warmth, tenderness, or erythema: Extend treatment and reassess for complications or resistant organisms 1

When MRSA Coverage is NOT Needed

Do not add MRSA coverage for typical nonpurulent cellulitis—MRSA is an uncommon cause of typical cellulitis even in hospitals with high MRSA prevalence. 1, 2 Adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases. 1 Combination therapy with trimethoprim-sulfamethoxazole plus cephalexin is no more efficacious than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage. 1, 6

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
• Known MRSA colonization or evidence of MRSA infection elsewhere 1
• Systemic inflammatory response syndrome (SIRS) 1

MRSA-Active Regimens (when indicated):

• Clindamycin 300-450 mg orally every 6 hours as monotherapy (covers both streptococci and MRSA, avoiding need for combination therapy) 1, 2
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (never use doxycycline as monotherapy—unreliable streptococcal coverage) 1, 2

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily—this hastens improvement by promoting gravity drainage of edema and inflammatory substances 1, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—treating these eradicates colonization and reduces recurrent infection risk 1, 2
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, obesity, and eczema 1, 2

Critical Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized or because MRSA prevalence is high in your area—beta-lactam treatment is successful in 96% of patients 1
• Do not extend treatment to 10-14 days based on residual erythema alone—some inflammation persists even after bacterial eradication 1
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy—their activity against beta-hemolytic streptococci is unreliable 1, 2
• Do not use fluoroquinolones (levofloxacin, moxifloxacin) as first-line agents—reserve these for patients with beta-lactam allergies to minimize resistance 1

Oral Administration Considerations

Dicloxacillin is best absorbed when taken on an empty stomach—administer at least 1 hour before or 2 hours after meals with at least 4 fluid ounces (120 mL) of water, and should not be taken in the supine position or immediately before going to bed. 3

Outpatient vs. Inpatient Management

Outpatient oral therapy is appropriate for mild cellulitis without: 1, 2

• Systemic inflammatory response syndrome (SIRS)
• Altered mental status or confusion
• Hemodynamic instability or hypotension
• Severe immunocompromise or neutropenia
• Concern for deeper or necrotizing infection

Hospitalization is indicated if any of these features are present. 1, 2