What antibiotics are recommended for treating skin infections?

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Antibiotic Recommendations for Skin Infections

For mild skin and soft tissue infections, first-line antibiotics include amoxicillin-clavulanic acid, cloxacillin, or cephalexin, while more severe infections require targeted therapy based on suspected pathogens and resistance patterns. 1

First-Line Antibiotics for Mild Skin Infections

The WHO Essential Medicines List recommends the following first-choice antibiotics for mild skin and soft tissue infections:

  • Amoxicillin-clavulanic acid (oral)
  • Cloxacillin (oral) - For oral administration, dicloxacillin and flucloxacillin are preferred due to better bioavailability
  • Cephalexin (oral) - Recently upgraded from second to first choice for skin and soft tissue infections 1

These antibiotics provide excellent coverage against the most common pathogens causing skin infections, particularly Staphylococcus aureus and Streptococcus species.

Treatment Based on Specific Infection Types

Uncomplicated Skin Infections

  • Duration: 5-7 days 2
  • First-line options:
    • Dicloxacillin 500 mg orally four times daily
    • Amoxicillin-clavulanic acid 875/125 mg orally twice daily
    • Cephalexin 500 mg orally four times daily 2

Diabetic Wound Infections

  • Mild infections: Dicloxacillin, clindamycin, cephalexin, levofloxacin, amoxicillin-clavulanic acid, or doxycycline 1
  • Moderate to severe infections: Levofloxacin, cefoxitin, ceftriaxone, ampicillin-sulbactam, moxifloxacin, ertapenem, tigecycline, or ciprofloxacin with clindamycin 1

Surgical Site Infections

  • Trunk/extremity infections: Oxacillin, nafcillin, cefazolin, cephalexin, sulfamethoxazole-trimethoprim, or vancomycin 1
  • Axilla/perineum infections: Ceftriaxone or a fluoroquinolone (ciprofloxacin or levofloxacin) combined with metronidazole 1

MRSA Considerations

For suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) infections:

  • Mild infections: Sulfamethoxazole-trimethoprim, clindamycin, doxycycline 1, 2
  • Moderate to severe infections: Linezolid, daptomycin, or vancomycin 1, 3

Clinical cure rates for MRSA skin infections with linezolid have been demonstrated at 79% compared to 73% for vancomycin 3.

Necrotizing Fasciitis (Severe Infection)

For this life-threatening infection, combination therapy is recommended:

  • Clindamycin plus piperacillin-tazobactam (with or without vancomycin), OR
  • Ceftriaxone plus metronidazole (with or without vancomycin) 1

Special Considerations

Penicillin Allergy

  • For non-severe allergies: Cephalexin (note: up to 10% of penicillin-allergic patients may also be allergic to cephalosporins) 2
  • For severe allergies (anaphylactic-type): Clindamycin (300-450 mg orally three times daily) 2, 4

Renal Impairment

  • Dose adjustment required for patients with creatinine clearance less than 30 ml/min when using antibiotics such as amoxicillin-clavulanic acid 2

Pregnancy

  • Amoxicillin and cephalexin are generally considered safe (Category B) 2

Treatment Duration

  • Uncomplicated skin infections: 5-7 days 2
  • Complicated skin infections: 10-14 days 3
  • Vancomycin-resistant infections: 14-28 days 3

Monitoring and Follow-up

  • Reassess patients within 48-72 hours to evaluate response to treatment 2
  • Consider hospitalization and broader antibiotic coverage if:
    • No improvement within 48 hours
    • Development of systemic symptoms
    • Extension of infection 2

Prevention of Recurrence

  • Identify and treat predisposing conditions (edema, obesity, eczema, venous insufficiency)
  • Optimize glycemic control in diabetic patients
  • Consider prophylactic antibiotics for patients with 3-4 episodes per year (options include oral penicillin or erythromycin twice daily) 2

Remember that complete eradication of the infection is crucial to prevent recurrence and complications, so patients should complete the full course of antibiotics as prescribed.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Erythema Nodosum and Cellulitis Treatment Guidelines

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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