What is the recommended protocol for oral antibiotics for skin infections?

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Oral Antibiotic Protocol for Skin Infections

Initial Assessment and Classification

The treatment protocol depends on whether the infection is purulent (with abscess/pus) or non-purulent (cellulitis/erysipelas), and the severity based on systemic signs of infection. 1, 2

Severity Classification

Assess for systemic inflammatory response syndrome (SIRS) criteria to determine severity 1:

  • Temperature >38°C or <36°C
  • Tachypnea >24 breaths/minute
  • Tachycardia >90 beats/minute
  • White blood cell count >12,000 or <4,000 cells/μL

Non-Purulent Infections (Cellulitis/Erysipelas)

Mild to Moderate Severity (No SIRS)

For uncomplicated cellulitis without purulent drainage, use oral antibiotics targeting streptococci and methicillin-susceptible Staphylococcus aureus (MSSA) as first-line therapy. 2

Preferred first-line agents: 1, 2

  • Cephalexin 500 mg every 6 hours (or 250 mg four times daily) 1, 3
  • Dicloxacillin 250-500 mg every 6 hours 1

Alternative agents for penicillin allergy (non-immediate hypersensitivity): 1

  • Cefazolin 1 g every 8 hours IV (if parenteral needed) 1
  • Amoxicillin-clavulanate 875/125 mg twice daily 1

Duration: 5 days if clinical improvement occurs; extend if no improvement 2

When to Add MRSA Coverage

Add empiric MRSA-active antibiotics if any of the following are present: 2

  • Penetrating trauma or injection drug use
  • Purulent drainage despite appearing non-purulent initially
  • Evidence of MRSA elsewhere on body
  • Nasal MRSA colonization
  • Failed initial beta-lactam therapy 1

MRSA-active oral options: 1, 2

  • Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily 1, 2
  • Doxycycline 100 mg twice daily 1, 2
  • Clindamycin 300-450 mg four times daily 1, 2

Important caveat: Clindamycin has potential for cross-resistance and emergence of resistance in erythromycin-resistant strains, with inducible resistance possible in MRSA 1


Purulent Infections (Abscesses, Furuncles, Carbuncles)

Mild Severity

Incision and drainage is the primary treatment for purulent infections, with antibiotics as adjunctive therapy only when indicated. 1, 2

Indications for adding antibiotics after drainage: 2

  • Fever or systemic signs present
  • Multiple lesions
  • Immunocompromised patient
  • Drainage alone has failed
  • Severe local symptoms or rapid progression 1

When antibiotics are indicated, use MRSA-active agents: 1, 2

  • Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily
  • Doxycycline 100 mg twice daily
  • Clindamycin 300-450 mg four times daily

Duration: 5 days if clinical improvement occurs 2

Moderate to Severe Purulent Infections

For patients with SIRS criteria, failed initial treatment, or markedly impaired host defenses, use MRSA-active antibiotics empirically. 1

Same MRSA-active oral agents as above, or consider IV therapy if meeting criteria for severe infection 1, 2


Special Situations

Impetigo and Ecthyma

Use a 7-day oral regimen with an agent active against S. aureus unless cultures yield streptococci alone (when penicillin is recommended). 1

For methicillin-susceptible infections: 1

  • Dicloxacillin 250 mg four times daily
  • Cephalexin 250 mg four times daily
  • Amoxicillin-clavulanate 875/125 mg twice daily

When MRSA is suspected or confirmed: 1

  • Doxycycline 100 mg twice daily
  • Clindamycin 300-400 mg four times daily
  • Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily

For limited lesions, topical therapy may suffice: 1

  • Mupirocin ointment applied twice daily
  • Retapamulin ointment applied twice daily

Bite Wounds (Animal or Human)

Amoxicillin-clavulanate is the antibiotic of choice for bite wounds due to coverage of both aerobic and anaerobic pathogens. 1, 2

Dosing: 875/125 mg twice daily 1

Alternative for penicillin allergy: 1

  • Moxifloxacin 400 mg daily (covers anaerobes as monotherapy)
  • Ciprofloxacin 500-750 mg twice daily OR levofloxacin 750 mg daily PLUS metronidazole 250-500 mg three times daily

Important: Administer tetanus toxoid if not vaccinated within 10 years (or 5 years for dirty wounds); Tdap preferred if not previously given 1

Recurrent Infections

For recurrent skin infections, implement a comprehensive approach: 2

  • Drain and culture early lesions
  • Treat with 5-10 day course based on culture results
  • Consider decolonization regimens: intranasal mupirocin twice daily for 5 days, daily chlorhexidine washes, daily decontamination of personal items 2

Criteria for IV Therapy/Hospitalization

Severe infections require IV therapy when any of the following are present: 2

  • Systemic inflammatory response syndrome (SIRS)
  • Hemodynamic instability or hypotension 1
  • Altered mental status
  • Concern for necrotizing infection
  • Severely immunocompromised status
  • Failed oral antibiotic treatment 1

IV regimens for severe infections: 2

  • Vancomycin 15-20 mg/kg every 8-12 hours (for MRSA coverage)
  • Cefazolin 1 g every 8 hours (for streptococcal/MSSA coverage)
  • Vancomycin PLUS piperacillin-tazobactam or carbapenem for broad polymicrobial coverage

Key Clinical Pearls

Common pitfalls to avoid:

  • Do not use first-generation cephalosporins, macrolides, clindamycin, or aminoglycosides for human bite wounds due to Eikenella corrodens resistance 1
  • Trimethoprim-sulfamethoxazole has poor activity against anaerobes; avoid as monotherapy for bite wounds 1
  • Cephalosporins are contraindicated in patients with immediate penicillin hypersensitivity (urticaria, angioedema, bronchospasm, anaphylaxis) 4
  • Most S. aureus strains are now penicillin-resistant; penicillin G is not appropriate for staphylococcal infections 4, 5

Twice-daily dosing enhances compliance: Cephalexin can be given as 500 mg every 12 hours for streptococcal pharyngitis, skin infections, and uncomplicated cystitis, improving medication adherence 3, 6, 5

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

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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