What are the treatment options for recalcitrant impetigo on the arms, trunk, and legs in a patient who has failed oral Cephalexin (Keflex)?

Treatment for Recalcitrant Impetigo After Failed Cephalexin Therapy

For recalcitrant impetigo that has failed oral cephalexin (Keflex) treatment, switch to oral clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) as these are the most effective second-line options for suspected MRSA infection. 1

Evaluation of Treatment Failure

When impetigo fails to respond to first-line cephalexin therapy, consider:

1. Potential MRSA infection: Treatment failure with cephalexin strongly suggests methicillin-resistant Staphylococcus aureus (MRSA) as the causative organism 2
2. Extent of infection: Widespread lesions on arms, trunk, and legs indicate more extensive disease requiring systemic therapy
3. Duration of previous treatment: Ensure adequate duration (7-10 days) of initial treatment was completed

Second-Line Treatment Options

Oral Antibiotics for MRSA Coverage

• Clindamycin (300mg three times daily for 7-10 days):

  • Excellent coverage against both MRSA and streptococci 2, 1
  • Good activity against staphylococci, streptococci, and anaerobes 2

• Trimethoprim-sulfamethoxazole (TMP-SMX) (160-800mg twice daily for 7-10 days):

  • Highly effective against MRSA 2, 1
  • Important limitation: Inadequate streptococcal coverage 1, 3
  • Consider combining with a beta-lactam if streptococcal infection is still suspected 2

• Doxycycline (100mg twice daily for 7-10 days):

  • Effective option for patients >8 years of age 1
  • Good activity against MRSA 2
  • Not recommended for children under 8 years due to risk of inhibiting bone growth 1

Alternative Options

• Linezolid (600mg twice daily for 7-10 days):

  • Superior clinical and microbiological cure rates compared to vancomycin for MRSA skin infections 2
  • Excellent tissue penetration and bioavailability 2
  • Higher cost may limit use as first-line therapy

• Mupirocin 2% topical ointment (applied three times daily for 5-7 days):

  • Consider as adjunctive therapy for accessible lesions 1
  • Shown to be as effective as oral erythromycin in limited disease 4
  • Not suitable as monotherapy for extensive disease

Treatment Algorithm

1. First choice: Oral clindamycin for 7-10 days

   • Provides coverage for both MRSA and streptococci
   • Monitor for gastrointestinal side effects

2. Alternative if clindamycin contraindicated: TMP-SMX for 7-10 days

   • Consider adding a beta-lactam (amoxicillin) if streptococcal coverage is needed
   • Avoid in patients with sulfa allergies

3. For patients >8 years with no other options: Doxycycline for 7-10 days

4. For severe cases or treatment failures: Consider consultation with infectious disease specialist for possible IV therapy options

Monitoring and Follow-up

• Evaluate clinical response within 48-72 hours of starting new therapy
• If no improvement is seen within 3-5 days, consider:
  • Obtaining bacterial culture and sensitivity testing
  • Alternative diagnosis
  • Possible need for intravenous antibiotics

Important Considerations

• Treatment duration should be 7-10 days based on clinical response 2, 1
• Topical antibiotics alone are insufficient for widespread impetigo involving multiple body regions 5
• Good hygiene practices are essential to prevent spread:
  • Keep lesions covered when possible
  • Use separate towels and linens
  • Practice good hand hygiene 1

Potential Pitfalls

• Failure to consider MRSA as the causative organism in recalcitrant impetigo
• Using penicillin which has been shown to be inferior to other antibiotics for impetigo 2, 5
• Inadequate duration of therapy (less than 7 days)
• Relying solely on topical therapy for extensive disease
• Not addressing underlying conditions that may predispose to recurrent infection (e.g., eczema, diabetes)

The evidence strongly supports switching to an anti-MRSA agent when cephalexin fails, with clindamycin offering the best balance of efficacy against both MRSA and streptococci for recalcitrant impetigo.