What is the appropriate treatment for a patient with a skin infection, considering factors such as age, medical history, and severity of the infection?

Treatment of Skin Infections

For typical uncomplicated skin infections, beta-lactam monotherapy with agents like cephalexin 500 mg every 6 hours or dicloxacillin 250-500 mg every 6 hours for 5 days is the standard of care, achieving 96% success rates without requiring MRSA coverage. 1, 2

Initial Assessment and Risk Stratification

Before selecting antibiotics, determine whether the infection is purulent or nonpurulent, as this fundamentally changes management:

• Purulent infections (abscesses, furuncles, carbuncles with visible pus or drainage) require incision and drainage as primary treatment, with antibiotics playing only a subsidiary role 1, 2
• Nonpurulent infections (cellulitis, erysipelas without drainage) respond to antibiotics as primary treatment 1, 2

Assess for specific MRSA risk factors that mandate coverage beyond standard beta-lactams:

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Evidence of MRSA infection elsewhere or known MRSA colonization 1, 2
• Systemic inflammatory response syndrome (fever >38°C, heart rate >90, respiratory rate >24, WBC <4,000 or >12,000) 1, 2

Antibiotic Selection Algorithm

For Uncomplicated Nonpurulent Infections (No MRSA Risk Factors)

First-line oral options (choose one):

• Cephalexin 500 mg every 6 hours 1, 3
• Dicloxacillin 250-500 mg every 6 hours 1, 2
• Amoxicillin (dose equivalent to above agents) 1, 2
• Penicillin V 250-500 mg four times daily 1, 2

These agents provide excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, which cause the vast majority of typical skin infections 1, 2, 4

Treatment duration: Exactly 5 days if clinical improvement occurs (reduced warmth, tenderness, erythema, and patient afebrile); extend only if symptoms have not improved 1, 2

For Infections Requiring MRSA Coverage

When specific risk factors are present, add MRSA-active therapy:

Oral combination regimens:

• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin) 1, 2
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1, 2

Single-agent MRSA coverage (covers both streptococci and MRSA):

• Clindamycin 300-450 mg every 6 hours—but use only if local MRSA clindamycin resistance rates are <10% 1, 2

Critical caveat: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1, 2

For Severe Infections Requiring Hospitalization

Hospitalize patients with any of the following:

• Systemic inflammatory response syndrome 1, 2
• Hypotension or altered mental status 1, 2
• Severe immunocompromise or neutropenia 1, 2
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissues, gas in tissue) 1, 2

IV antibiotic regimens for complicated infections:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 2
• Linezolid 600 mg IV twice daily (equally effective alternative, A-I evidence) 1, 2
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1, 2
• Clindamycin 600 mg IV every 8 hours (A-III evidence, only if local resistance <10%) 1, 2

For severe infections with systemic toxicity or suspected necrotizing fasciitis, use mandatory broad-spectrum combination therapy:

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

Treatment duration for severe infections: 7-14 days, guided by clinical response 1, 2

Special Populations and Circumstances

Bite Wounds (Animal or Human)

• Amoxicillin-clavulanate 875/125 mg twice daily provides single-agent coverage for polymicrobial oral flora 1, 2
• Irrigation and debridement of necrotic tissue are the most important preventive factors 1
• Consider post-exposure prophylaxis for HBV, HCV, and HIV in human bites 1

Diabetic Foot Infections

These require broader coverage and longer duration due to polymicrobial nature:

• Mild infections: Dicloxacillin, cephalexin, amoxicillin-clavulanate, or levofloxacin 1, 2
• Moderate infections: Amoxicillin-clavulanate, levofloxacin, ceftriaxone, ampicillin-sulbactam, or ertapenem 1, 2
• Severe infections: Piperacillin-tazobactam, imipenem-cilastatin, or vancomycin plus ceftazidime with or without metronidazole 1, 2
• Plain radiographs should be obtained to assess for osteomyelitis 1

Immunocompromised Patients

• Biopsy or aspiration of lesions for histological and microbiological evaluation should be implemented as an early diagnostic step 1
• Empiric therapy must be initiated immediately based on underlying immune defect, morphology of lesions, and local resistance patterns 1
• Consider atypical organisms including fungi, viruses, and parasites 1

Pediatric Patients

Oral dosing for uncomplicated infections:

• Cephalexin 25-50 mg/kg/day divided every 6-12 hours 3, 5
• For streptococcal pharyngitis and skin infections, may divide total daily dose every 12 hours 3
• Clindamycin 10-13 mg/kg/dose every 6-8 hours (if MRSA coverage needed and local resistance <10%) 2

IV dosing for hospitalized children:

• Vancomycin 15 mg/kg IV every 6 hours (first-line, A-II evidence) 2
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (for stable children without bacteremia, A-II evidence) 2

Topical therapy for minor infections:

• Mupirocin 2% ointment for impetigo and secondarily infected lesions 2, 6
• Apply three times daily for 3-5 days; discontinue if no improvement 6

Essential Adjunctive Measures

These non-antibiotic interventions significantly accelerate recovery and prevent recurrence:

• Elevation of affected extremity above heart level for at least 30 minutes three times daily promotes gravitational drainage 1, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration; treating these eradicates colonization and reduces recurrence 1, 2
• Address predisposing conditions: venous insufficiency, lymphedema, chronic edema, obesity, eczema 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 2

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—MRSA is uncommon even in high-prevalence settings, and beta-lactam monotherapy succeeds in 96% of cases 1, 2
• Do not extend treatment to 7-14 days based on tradition—5 days is sufficient for uncomplicated infections if clinical improvement has occurred 1, 2
• Do not continue antibiotics until complete wound healing—antibiotics can be discontinued once clinical signs of infection resolve 1
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis due to unreliable streptococcal coverage 1, 2
• Do not delay surgical consultation if any signs of necrotizing infection are present—these progress rapidly and require debridement 2

Penicillin Allergy Considerations

For patients reporting penicillin allergy:

• Cross-reactivity between penicillins and cephalosporins is only 2-4%, primarily based on R1 side chain similarity rather than the beta-lactam ring 2
• Cephalosporins with dissimilar side chains can be used safely in patients with cephalosporin allergy 2
• For true severe penicillin/cephalosporin allergy: Use clindamycin 300-450 mg every 6 hours (if local resistance <10%) or fluoroquinolones (levofloxacin, moxifloxacin) for beta-lactam-allergic patients 1, 2