What is the first‑line treatment for uncomplicated impetigo, including topical and oral options?

Treatment of Impetigo

First-Line Treatment for Limited Disease

For uncomplicated impetigo with limited lesions, topical mupirocin 2% ointment applied twice to three times daily for 5-7 days is the first-line treatment. 1, 2

• Mupirocin is the most effective topical agent for impetigo caused by both S. aureus and S. pyogenes, with cure rates 6-fold higher than placebo. 1, 2
• Apply mupirocin twice daily for 5 days (this is the standard FDA-approved regimen). 1, 2
• Topical retapamulin 1% ointment twice daily for 5 days is an acceptable alternative for patients aged ≥9 months, covering up to 100 cm² in adults or 2% total body surface area in children. 2, 3

Critical Caveat About Topical Therapy

• Do not use bacitracin or neomycin—they are considerably less effective and should not be used for impetigo. 1
• Do not use topical clindamycin cream (the acne formulation)—it lacks FDA indication for impetigo and has insufficient systemic absorption to treat bacterial skin infections. 1

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When to Switch to Oral Antibiotics

Oral antibiotics are indicated when: 1, 2

• Impetigo is extensive (numerous lesions)
• No improvement after 3-5 days of topical therapy
• Lesions involve the face, eyelid, or mouth
• Systemic symptoms are present
• Need to limit spread to others (outbreaks, athletes, close-contact settings)
• Patient is immunocompromised (lower threshold for oral therapy)

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Oral Antibiotic Options

For Presumed Methicillin-Susceptible S. aureus (MSSA)

First-line oral antibiotics: 1, 2

• Cephalexin: 250-500 mg four times daily for adults; 25-50 mg/kg/day divided into 4 doses for children, for 7 days
• Dicloxacillin: 250 mg four times daily for adults; 25-50 mg/kg/day divided into 4 doses for children, for 7 days
• Co-amoxiclav (amoxicillin-clavulanate): An acceptable alternative when cephalexin or dicloxacillin are not suitable, for 7 days 2

For Suspected or Confirmed MRSA

When MRSA is suspected (high local prevalence, treatment failure, or confirmed by culture): 1, 2

• Clindamycin: 300-450 mg three to four times daily for adults; 20-30 mg/kg/day divided into 3 doses for children, for 7 days
• Trimethoprim-sulfamethoxazole (TMP-SMX): 1-2 double-strength tablets twice daily for adults; 8-12 mg/kg/day (trimethoprim component) divided into 2 doses for children, for 7 days
• Doxycycline: Only for children >8 years old (2-4 mg/kg/day divided into 2 doses for 7 days) due to risk of permanent dental staining 1, 2

Critical Pitfalls to Avoid

• Penicillin alone is NOT effective for impetigo—it lacks adequate coverage against S. aureus, which is now the predominant pathogen. 1, 2
• Amoxicillin alone should not be used—it lacks adequate S. aureus coverage. 2
• Cefdinir should not be used when MRSA is suspected or confirmed. 2
• Oral antibiotics require 7 days of treatment, not the shorter 5-day course used for topical agents. 1, 2

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Special Populations and Allergy Considerations

Penicillin Allergy

• Use cephalexin (first-generation cephalosporin) except in patients with type 1 hypersensitivity reactions (anaphylaxis/hives). 1, 2
• For true penicillin allergy with immediate hypersensitivity, use clindamycin or TMP-SMX. 1, 2

Pregnancy

• Cephalexin is considered a safe alternative for pregnant patients. 1, 2

Children

• Avoid tetracyclines (doxycycline) in children <8 years due to risk of permanent dental staining. 1, 2

Immunocompromised Patients

• Use a lower threshold for oral antibiotics. 1
• Monitor closely for treatment failure or deeper infection. 1
• Consider longer treatment duration based on clinical response. 1

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When to Obtain Cultures

Cultures are not routinely necessary for typical limited impetigo, but obtain them when: 1

• Treatment failure occurs
• MRSA is suspected
• Recurrent infections
• Immunocompromised patients
• During outbreaks

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Infection Control and Prevention

To prevent spread: 1, 2

• Keep lesions covered with clean, dry bandages
• Maintain good personal hygiene with regular handwashing
• Avoid sharing personal items that contact the skin (towels, equipment)
• Athletes should be excluded from participation until 24 hours after initiation of effective antimicrobial therapy, and lesions must be covered 1

During outbreaks: 1, 2

• Use systemic antimicrobials to help eliminate nephritogenic strains of S. pyogenes from the community
• Consider decolonization strategies using topical nasal mupirocin for S. aureus carriers
• Involve public health authorities in outbreak management

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Monitoring and Follow-Up

If no improvement by 3-5 days of appropriate therapy, reassess for: 1

• MRSA infection requiring alternative antibiotics
• Deeper or more complex infection than initially estimated
• Non-compliance with therapy
• Antibiotic resistance (obtain cultures)