What is the first‑line treatment for impetigo, including topical therapy for limited lesions and oral antibiotics for extensive disease, facial or intertriginous involvement, methicillin‑resistant Staphylococcus aureus risk, and for pregnant or lactating patients?

Impetigo Treatment

First-Line Treatment Based on Disease Extent

For limited impetigo (few lesions), use topical mupirocin 2% ointment applied three times daily for 5-7 days; for extensive disease, facial/intertriginous involvement, or systemic symptoms, initiate oral antibiotics immediately. 1, 2

Topical Therapy (Limited Disease Only)

• Mupirocin 2% ointment applied to lesions twice to three times daily is the most effective topical agent for both S. aureus and S. pyogenes 1, 2
• Retapamulin ointment applied twice daily is an alternative topical option for limited lesions 1, 2
• Topical therapy is appropriate only when: lesions are few in number, not on face/mouth/eyelids, patient can comply with application schedule, and no systemic symptoms are present 2, 3
• Switch to oral antibiotics if no improvement after 3-5 days of topical therapy 2, 3

Oral Antibiotic Therapy (Extensive Disease or Treatment Failure)

Indications requiring oral antibiotics include: 2, 3

• Extensive disease (multiple or widespread lesions)
• Facial, eyelid, mouth, or intertriginous involvement
• Failure of topical therapy after 3-5 days
• Systemic symptoms present
• Need to limit spread to others (outbreaks, athletes)
• Patient preference or inability to apply topical therapy

For Presumed Methicillin-Susceptible S. aureus (MSSA):

First-line oral options: 1, 2

• Dicloxacillin 250 mg four times daily (adults) or 12-25 mg/kg/day in 4 divided doses (children)
• Cephalexin 250-500 mg four times daily (adults) or 25-50 mg/kg/day in 4 divided doses (children)
• Amoxicillin-clavulanate 875/125 mg twice daily (adults) or 25 mg/kg/day of amoxicillin component in 2 divided doses (children)

Duration: 5-10 days 2, 3

For Suspected or Confirmed MRSA:

MRSA coverage is indicated when: 2, 4

• High MRSA prevalence in your area
• Treatment failure with beta-lactam antibiotics
• Known MRSA colonization
• Recurrent infections

Recommended MRSA-active agents: 1, 2

• Clindamycin 300-450 mg three to four times daily (adults) or 10-20 mg/kg/day in 3 divided doses (children) - preferred if local clindamycin resistance <10%
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily (adults) or 8-12 mg/kg/day (based on trimethoprim) in 2 divided doses (children) - note: inadequate for streptococcal coverage alone 4
• Doxycycline 100 mg twice daily (adults only, avoid in children <8 years) 1, 2

Duration: 7-10 days 2, 3

Special Populations

Pregnant or Lactating Patients:

• Cephalexin is generally considered safe and is the preferred oral agent 2, 3
• Avoid tetracyclines (doxycycline) completely 2
• Topical mupirocin is safe for localized disease 2

Children:

• Avoid doxycycline and all tetracyclines in children <8 years 1, 2, 3
• Cephalexin is preferred due to suspension availability and less frequent dosing 1
• Clindamycin is an important option for pediatric MRSA 2

Penicillin-Allergic Patients:

• Clindamycin is the preferred alternative 3
• Avoid cephalosporins if type 1 hypersensitivity (anaphylaxis/hives) to beta-lactams 3
• For MRSA risk, use clindamycin or trimethoprim-sulfamethoxazole 1, 2

Critical Pitfalls to Avoid

Penicillin alone is NOT effective for impetigo as it lacks adequate S. aureus coverage 2, 3

Macrolides (erythromycin) have increasing resistance rates and should be used with caution; they are no longer reliably effective 1, 2, 4

Bacitracin and neomycin are considerably less effective and should not be used 3

Topical clindamycin cream (for acne) is NOT appropriate for impetigo treatment - it lacks FDA indication and has insufficient bioavailability for bacterial skin infections 3

When to Obtain Cultures

Cultures are not routinely necessary for typical limited impetigo, but obtain cultures when: 2, 3

• Treatment failure after appropriate therapy
• MRSA suspected or confirmed
• Recurrent infections
• Immunocompromised patients
• Outbreak situations

Monitoring and Follow-Up

Reassess if no improvement by 3-5 days and consider: 2, 3

• MRSA infection requiring alternative antibiotics
• Deeper or more complex infection than initially estimated
• Non-compliance with therapy
• Antibiotic resistance (including mupirocin resistance in high MRSA areas)

For athletes and organized sports: exclude from participation until 24 hours after initiation of effective antimicrobial therapy, and lesions must be covered with clean, dry bandages 3

Infection Control Measures

Implement these measures regardless of treatment choice: 3

• Keep lesions covered with clean, dry bandages
• Maintain good personal hygiene with regular handwashing
• Avoid sharing personal items that contact the skin
• During outbreaks, consider decolonization strategies using topical nasal mupirocin for S. aureus carriers 3