What antibiotics are recommended for a patient with a superficial skin infection, considering potential penicillin allergy and varying severity of infection?

Antibiotics for Superficial Skin Infections

For typical uncomplicated superficial skin infections (impetigo, erysipelas, cellulitis), use beta-lactam monotherapy targeting Gram-positive bacteria—specifically oral cephalexin 500 mg four times daily, dicloxacillin 250-500 mg every 6 hours, or amoxicillin for 5 days if clinical improvement occurs. 1, 2

First-Line Treatment Algorithm

For Non-Purulent Superficial Infections (Impetigo, Erysipelas, Cellulitis)

Beta-lactam monotherapy is successful in 96% of patients and remains the standard of care. 2 The primary pathogens are beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus. 1

Recommended oral agents include: 1, 2

• Cephalexin 500 mg orally every 6 hours 2, 3
• Dicloxacillin 250-500 mg every 6 hours 2, 4
• Amoxicillin (dose varies by severity) 2
• Penicillin V 250-500 mg four times daily (particularly for erysipelas) 1, 2

For hospitalized patients requiring IV therapy: 2

• Cefazolin 1-2 g IV every 8 hours (preferred) 2, 5
• Oxacillin 2 g IV every 6 hours (alternative) 2

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 2 This represents high-quality evidence from randomized controlled trials showing 5-day courses are as effective as 10-day courses for uncomplicated cellulitis. 2

When to Add MRSA Coverage

Do NOT routinely add MRSA coverage for typical nonpurulent cellulitis, as MRSA is an uncommon cause even in high-prevalence settings. 2 However, empiric MRSA therapy is indicated when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Known MRSA colonization or previous MRSA infection 1, 2
• Failure to respond to first-line beta-lactam therapy 1
• Systemic inflammatory response syndrome (SIRS) 2

When MRSA coverage is needed, use: 2

• Clindamycin 300-450 mg orally every 6 hours (provides single-agent coverage for both streptococci and MRSA, but only if local resistance <10%) 2, 4
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam 2
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 2

Critical caveat: Doxycycline or trimethoprim-sulfamethoxazole should NEVER be used as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 2

Management of Penicillin Allergy

For patients with penicillin allergy (except immediate hypersensitivity reactions), cephalosporins remain an option, as cross-reactivity is only 2-4%. 2 However, avoid cephalexin in patients with confirmed immediate-type amoxicillin allergy due to identical R1 side chains. 2

For true penicillin-allergic patients: 1, 2

• Clindamycin 300-450 mg orally every 6 hours (if local MRSA resistance <10%) 2
• First-generation cephalosporin (if no immediate hypersensitivity) 1, 4

For patients allergic to both penicillins and cephalosporins: 2

• Clindamycin monotherapy provides coverage for both streptococci and MRSA 2
• Linezolid 600 mg orally twice daily (expensive, reserved for complicated cases) 2

Simple Abscesses and Boils

Incision and drainage is the primary treatment for simple abscesses or boils; do NOT use antibiotics for simple abscesses that can be adequately drained. 1 Antibiotics play only a subsidiary role when drainage is the primary intervention. 1

Severe Infections Requiring Hospitalization

For patients with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required: 2

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 2, 6
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 2
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 2

Indications for hospitalization include: 2

• Systemic inflammatory response syndrome (fever >38°C, tachycardia, tachypnea) 2
• Hypotension or hemodynamic instability 2
• Altered mental status or confusion 2
• Severe immunocompromise or neutropenia 2
• Concern for necrotizing infection 2

Treatment duration for severe infections is 7-14 days, guided by clinical response. 2

Essential Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravitational drainage of edema and inflammatory substances. 2 This simple intervention is often neglected but critical for optimal outcomes. 2

Treat predisposing conditions: 2

• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration 2
• Address venous insufficiency and lymphedema with compression stockings once acute infection resolves 2
• Manage chronic edema and obesity 2

Common Pitfalls to Avoid

Do not reflexively add MRSA coverage simply because the patient is hospitalized—beta-lactam monotherapy remains appropriate for uncomplicated cellulitis even in the inpatient setting if no MRSA risk factors are present. 2

Do not extend treatment to 10-14 days based on residual erythema alone—some inflammation persists even after bacterial eradication, and extending antibiotics beyond 5 days without clinical indication increases resistance without improving outcomes. 2

Do not use combination therapy when monotherapy is appropriate—this increases adverse effects and antibiotic resistance without benefit. 2