What is the second-line treatment for impetigo if Keflex (Cephalexin) is ineffective?

Second-Line Treatment for Impetigo After Cephalexin Failure

For impetigo that has not responded to Keflex (cephalexin), the recommended second-line treatment is clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), or doxycycline, with clindamycin being preferred when both Staphylococcus aureus and Streptococcus species need to be covered. 1, 2

Understanding Treatment Failure with Cephalexin

When cephalexin fails to treat impetigo, consider these possibilities:

• Methicillin-resistant Staphylococcus aureus (MRSA) infection
• Macrolide-resistant streptococcal infection
• Mixed bacterial infection
• Deeper infection than initially assessed

Second-Line Treatment Options

Preferred Agents:

1. Clindamycin: 300-450 mg orally three times daily for 5-7 days

   • Effective against both MRSA and streptococci
   • Excellent option when both pathogens need coverage 1

2. Trimethoprim-Sulfamethoxazole (TMP-SMX): 1-2 DS tablets orally twice daily for 5-7 days

   • Excellent coverage for MRSA
   • Note: May be inadequate for streptococcal infections alone 2

3. Doxycycline: 100 mg twice daily for 5-7 days

   • Effective against many MRSA strains
   • Should be avoided in children under 8 years and pregnant women 3

Topical Options:

• Mupirocin 2%: Apply to affected areas three times daily for 5-7 days
• Retapamulin 1%: Apply to affected areas twice daily for 5 days

Topical therapy is appropriate for limited disease (fewer than 5 lesions or area <2% body surface area) 1, 4

Treatment Algorithm Based on Clinical Presentation

1. Limited disease (few lesions, no systemic symptoms):

   • Try topical mupirocin or retapamulin first
   • Consider obtaining culture before starting new therapy

2. Extensive disease (multiple lesions, larger affected areas):

   • Start oral clindamycin if both MRSA and streptococcal coverage needed
   • Consider TMP-SMX if MRSA is strongly suspected
   • Obtain culture and susceptibility testing

3. Severe infection (systemic symptoms, rapidly progressing):

   • Consider hospitalization for IV antibiotics (vancomycin, linezolid, or daptomycin) 1
   • Obtain culture and susceptibility testing

Special Considerations

• Children: Adjust dosing appropriately; avoid doxycycline in children under 8 years
• Pregnant women: Avoid TMP-SMX in late pregnancy and doxycycline throughout pregnancy 3
• Immunocompromised patients: Consider broader coverage and longer treatment duration

Monitoring and Follow-up

• Patients should show improvement within 48-72 hours of starting appropriate therapy
• If no improvement after 72 hours, reevaluate diagnosis and consider:
  • Obtaining cultures if not done initially
  • Changing antibiotic therapy based on susceptibility results
  • Evaluating for deeper infection or complications 3

Common Pitfalls to Avoid

• Failing to obtain cultures in treatment failures
• Continuing the same antibiotic class after initial treatment failure
• Not considering MRSA in recurrent or non-responsive cases
• Using penicillin alone, which is ineffective against most S. aureus strains 2, 5
• Treating for too short a duration (5-7 days is typically required)

Remember that the increasing prevalence of antibiotic-resistant bacteria has changed empiric treatment considerations for impetigo, with MRSA, macrolide-resistant streptococci, and mupirocin-resistant strains all documented 2.