What antibiotics are used to treat skin infections?

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Antibiotic Treatment for Skin Infections

First-Line Oral Antibiotics for Uncomplicated Infections

For mild, non-purulent skin infections (cellulitis), cephalexin 500 mg every 6 hours or dicloxacillin 250-500 mg every 6 hours are the recommended first-line oral antibiotics, targeting streptococci and methicillin-susceptible Staphylococcus aureus (MSSA). 1, 2, 3

Standard Oral Regimens for Non-Purulent Infections

  • Cephalexin: 500 mg four times daily (every 6 hours) for adults; 25-50 mg/kg/day in divided doses for children 1, 4
  • Dicloxacillin: 250-500 mg four times daily for adults; 12 mg/kg/day in 4 divided doses for children 1, 3
  • Amoxicillin-clavulanate: 875/125 mg twice daily as an alternative first-line option 1, 2
  • Clindamycin: 300-450 mg three times daily for adults; 10-20 mg/kg/day in 3 divided doses for children (useful in penicillin allergy) 1, 3

Treatment duration is 5 days if clinical improvement occurs, with extension if no improvement is seen. 1, 2


MRSA Coverage: When and What to Use

Indications for MRSA-Active Antibiotics

Add MRSA coverage when: 2

  • Purulent drainage is present
  • Penetrating trauma or injection drug use history
  • Evidence of MRSA elsewhere on the body
  • Known nasal MRSA colonization
  • Failed initial therapy with beta-lactams

MRSA-Active Oral Options

  • Trimethoprim-sulfamethoxazole: 1-2 double-strength tablets twice daily 1, 2, 3
  • Doxycycline: 100 mg twice daily (avoid in children <8 years) 1, 3
  • Clindamycin: 300-450 mg three times daily 1, 3

Note: Clindamycin has potential for cross-resistance with erythromycin-resistant strains and inducible resistance in MRSA, so use cautiously. 1


Purulent Infections (Abscesses, Furuncles)

Incision and drainage is the primary treatment for purulent infections, with antibiotics serving as adjunctive therapy only. 2

When to Add Antibiotics to Drainage

Antibiotics are indicated when: 2

  • Fever or systemic signs present
  • Multiple lesions found
  • Patient is immunocompromised
  • Drainage alone has failed

Use MRSA-active antibiotics (trimethoprim-sulfamethoxazole, doxycycline, or clindamycin) for purulent infections requiring antibiotic therapy. 2


Severe Infections Requiring IV Therapy

Hospitalization Criteria

Admit patients with: 1, 2

  • Systemic inflammatory response syndrome (SIRS)
  • Hemodynamic instability
  • Altered mental status
  • Concern for necrotizing infection
  • Severe immunocompromise
  • Failed outpatient therapy

IV Antibiotic Regimens

For severe MSSA infections:

  • Nafcillin or oxacillin: 1-2 g every 4 hours IV (parenteral drug of choice) 1, 3
  • Cefazolin: 1 g every 8 hours IV (for penicillin-allergic patients without immediate hypersensitivity) 1, 2

For severe MRSA infections:

  • Vancomycin: 15-20 mg/kg every 8-12 hours IV (parenteral drug of choice for MRSA) 1, 2
  • Linezolid: 600 mg every 12 hours IV or PO (bacteriostatic, expensive, no cross-resistance) 1, 3
  • Daptomycin: 4 mg/kg every 24 hours IV (bactericidal, monitor for myopathy) 1

For severe polymicrobial or necrotizing infections:

  • Vancomycin plus piperacillin-tazobactam (3.375 g every 6 hours or 4.5 g every 8 hours IV) 1, 5
  • Vancomycin plus imipenem/meropenem (imipenem 500 mg every 6 hours IV or meropenem 1 g every 8 hours IV) 1, 5
  • Ceftriaxone plus metronidazole (with or without vancomycin) for mixed aerobic-anaerobic infections 1

Special Situations

Impetigo (Superficial Infection)

For limited lesions: 1

  • Mupirocin ointment: Apply to lesions 3 times daily (topical therapy sufficient)

For widespread impetigo requiring systemic therapy: 1

  • Dicloxacillin 250 mg four times daily
  • Cephalexin 250 mg four times daily
  • Erythromycin 250 mg four times daily (if susceptible)

Necrotizing Fasciitis

Prompt surgical consultation is mandatory for suspected necrotizing fasciitis. 1

  • For documented Group A Streptococcal infection: Penicillin plus clindamycin 1, 5
  • For polymicrobial necrotizing infection: Clindamycin plus piperacillin-tazobactam (with or without vancomycin) 1

Clindamycin is critical in toxin-mediated infections because it inhibits bacterial protein synthesis, reducing toxin production. 1

Diabetic Foot Infections

Mild infections: 1

  • Dicloxacillin, clindamycin, cephalexin, levofloxacin, or amoxicillin-clavulanate
  • Add trimethoprim-sulfamethoxazole if MRSA suspected

Moderate to severe infections: 1

  • Levofloxacin, ceftriaxone, ampicillin-sulbactam, ertapenem, or imipenem-cilastatin
  • Add linezolid, daptomycin, or vancomycin if MRSA confirmed

Animal or Human Bites

  • Amoxicillin-clavulanate: 875/125 mg twice daily PO 3
  • Ampicillin-sulbactam: 1.5-3.0 g every 6-8 hours IV for severe infections 3

Recurrent Infections

For patients with 3-4 episodes of cellulitis per year despite treating predisposing factors, prophylactic antibiotics should be considered. 1

Prophylactic Regimens

  • Oral penicillin or erythromycin twice daily for 4-52 weeks 1
  • Intramuscular benzathine penicillin every 2-4 weeks 1

Decolonization for Recurrent MRSA

  • Intranasal mupirocin twice daily for 5 days 2
  • Daily chlorhexidine washes 2
  • Daily decontamination of personal items 2

Critical Pitfalls to Avoid

  • Do not use oral anti-staphylococcal penicillins (nafcillin, oxacillin) due to poor oral bioavailability—use dicloxacillin or flucloxacillin instead for oral therapy. 1
  • Avoid cephalosporins in patients with immediate penicillin hypersensitivity (urticaria, angioedema, bronchospasm, anaphylaxis). 6
  • Do not use rifampicin or fusidic acid as single agents for MRSA—resistance develops rapidly; always use combination therapy. 6
  • Examine interdigital toe spaces in lower-extremity cellulitis—treating toe web abnormalities (fissuring, scaling, maceration) reduces recurrence risk. 1
  • For streptococcal infections, treat for minimum 10 days to prevent rheumatic fever. 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Local Skin Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Antibiotic Treatment for Skin and Soft Tissue Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Antibiotic Therapy for Soft Tissue Infections with Gut Tissue Involvement

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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