What are the first‑line treatment options and dosing for impetigo, and when should topical versus oral antibiotics be used?

Impetigo Treatment: First-Line Options and Topical vs. Oral Antibiotic Selection

For limited impetigo (few lesions), topical mupirocin 2% ointment applied twice daily for 5 days is the first-line treatment and is superior to oral antibiotics; for extensive disease (numerous lesions or outbreaks), oral cephalexin or dicloxacillin for 7 days is recommended. 1, 2

Treatment Algorithm Based on Disease Extent

Limited Disease (Few Lesions, Localized)

Topical therapy is first-line and more effective than oral antibiotics:

• Mupirocin 2% ointment: Apply twice daily for 5 days 1, 2

  • FDA-approved for impetigo caused by S. aureus and S. pyogenes 2
  • Achieves cure rates 6-fold higher than placebo 1
  • Effective in >90% of cases 3

• Retapamulin 1% ointment: Apply twice daily for 5 days (alternative option) 1, 4

  • FDA-approved for patients ≥9 months old 4
  • Can treat up to 100 cm² in adults or 2% total body surface area in children 4
  • Only covers methicillin-susceptible S. aureus 4

Extensive Disease (Numerous Lesions, Widespread, or Outbreaks)

Oral antibiotics are required when topical therapy is impractical:

First-Line Oral Options (Presumed Methicillin-Susceptible S. aureus/MSSA):

• Cephalexin: 25-50 mg/kg/day divided into 4 doses for 7 days (children); 250-500 mg four times daily (adults) 1

• Dicloxacillin: 25-50 mg/kg/day divided into 4 doses for 7 days (children); 250 mg four times daily (adults) 1

Alternative Oral Options (When MRSA is Suspected):

• Clindamycin: 20-30 mg/kg/day divided into 3 doses for 7 days (children); 300-450 mg three to four times daily (adults) 1

  • Use when local clindamycin resistance rate is <10% 5

• Trimethoprim-sulfamethoxazole (TMP-SMX): 8-12 mg/kg/day (based on trimethoprim component) divided into 2 doses for 7 days (children); 1-2 double-strength tablets twice daily (adults) 1

  • Critical caveat: TMP-SMX provides inadequate streptococcal coverage and should be combined with a β-lactam (e.g., amoxicillin) if streptococcal infection cannot be ruled out 6

• Doxycycline: 2-4 mg/kg/day divided into 2 doses for 7 days (children >8 years); standard adult dosing 1

  • Avoid in children <8 years due to permanent dental staining risk 5, 1

Critical Decision Points: When to Use Topical vs. Oral Antibiotics

Use topical antibiotics when:

• Lesions are limited and localized 1
• Patient can apply medication reliably 1
• No systemic signs of infection are present 1

Use oral antibiotics when:

• Numerous lesions are present 1
• During outbreaks to decrease transmission 1
• Topical therapy has failed 1
• Patient has diabetes or immunosuppression (lower threshold for systemic therapy) 1
• Bullous impetigo with extensive involvement 1

Important Dosing and Duration Distinctions

• Topical therapy duration: 5 days 1, 2, 4
• Oral therapy duration: 7 days (not 5 days—this is a common error) 1

MRSA Considerations

In areas with high MRSA prevalence, empiric therapy should cover MRSA until culture results are available: 1

• Clindamycin, TMP-SMX, or doxycycline (>8 years) are appropriate choices 5, 1
• Cefdinir should NOT be used when MRSA is suspected or confirmed 1
• Mupirocin and retapamulin cover methicillin-susceptible S. aureus only 4, 6

Common Pitfalls to Avoid

Antibiotics that should NOT be used:

• Penicillin alone: Seldom effective and should only be used when cultures confirm streptococci alone 1, 7
• Amoxicillin alone: Lacks adequate S. aureus coverage, which is now the predominant pathogen 1
• Topical disinfectants: Inferior to antibiotics with little evidence of benefit 1, 7

Penicillin allergy management:

• Cephalexin can be used except in patients with immediate hypersensitivity reactions 1
• Clindamycin is an alternative for true penicillin allergy 1

Adjunctive Measures

• Keep lesions covered with clean, dry bandages to prevent spread 1
• Apply plain petrolatum ointment over open erosions after bullae have deroofed 1
• Maintain good hand hygiene 1
• Avoid sharing personal items that contact skin 1