What is the recommended treatment for impetigo, including topical and oral antibiotics, dosing, and adjustments for extensive disease, MRSA risk, and penicillin allergy?

Impetigo Treatment

First-Line Treatment Based on Disease Extent

For limited impetigo (few lesions), topical mupirocin 2% ointment applied twice daily for 5 days is the superior first-line treatment, achieving cure rates 6-fold higher than placebo and outperforming oral antibiotics. 1, 2

For extensive impetigo (numerous lesions), oral cephalexin is the recommended first-line antibiotic at 250-500 mg four times daily for adults or 25-50 mg/kg/day divided into 4 doses for children, continued for 7 days. 1

Topical Therapy Algorithm

• Mupirocin 2% ointment twice daily for 5 days is highly effective for limited disease, with clinical efficacy rates of 71-93% versus 35% for placebo 2
• Retapamulin 1% ointment twice daily for 5 days is an alternative for patients ≥9 months old, covering up to 100 cm² in adults or 2% total body surface area in children 1
• Topical therapy should be reserved for patients with limited lesions; oral therapy is preferred during outbreaks to decrease transmission 1

Oral Therapy for Extensive Disease (Presumed MSSA)

• Cephalexin: 250-500 mg four times daily (adults) or 25-50 mg/kg/day in 4 divided doses (children) for 7 days 1
• Dicloxacillin: 250 mg four times daily (adults) or 25-50 mg/kg/day in 4 divided doses (children) for 7 days 1
• Amoxicillin-clavulanate: 875/125 mg twice daily (adults) or 25 mg/kg/day of amoxicillin component in 2 divided doses (children) for 7 days 1, 3

MRSA Coverage: When and How to Adjust

Empiric MRSA coverage should be initiated when patients have purulent drainage, prior treatment failure, or reside in areas with high community-acquired MRSA prevalence (>10%). 4, 1

MRSA-Active Oral Antibiotics

• Clindamycin: 300-450 mg three to four times daily (adults) or 20-30 mg/kg/day in 3 divided doses (children) for 7 days 1, 3
• Trimethoprim-sulfamethoxazole (TMP-SMX): 1-2 double-strength tablets twice daily (adults) or 8-12 mg/kg/day (trimethoprim component) in 2 divided doses (children) for 7 days 1, 3
• Doxycycline: 100 mg twice daily (adults) or 2-4 mg/kg/day in 2 divided doses (children >8 years) for 7 days 1

Cefdinir and other third-generation cephalosporins should never be used when MRSA is suspected, documented, or confirmed, as they lack MRSA activity. 1

Penicillin Allergy Management

For patients with non-immediate penicillin hypersensitivity (e.g., delayed rash), cephalexin can be safely used as cross-reactivity is <5%. 1

For patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, urticaria), switch to clindamycin 300-450 mg three to four times daily (adults) or 20-30 mg/kg/day in 3 divided doses (children) for 7 days. 1

• Macrolides (erythromycin, azithromycin) have increasing resistance rates and should be used with caution 4, 5
• Penicillin alone is seldom effective and should only be used when cultures confirm streptococci alone 1

Special Populations

Pediatric Considerations

• Tetracyclines (doxycycline) are absolutely contraindicated in children <8 years due to permanent dental staining risk 1, 3
• Cephalexin liquid suspension is more practical than dicloxacillin for children due to simpler dosing 1

Pregnancy and Breastfeeding

• Cephalexin and dicloxacillin are safe during pregnancy and breastfeeding, as first-generation cephalosporins are secreted into breast milk at very low concentrations 1
• TMP-SMX and doxycycline are acceptable for short-term therapy in breastfeeding mothers, but avoid TMP-SMX in neonates ≤28 days, jaundiced infants, or those with G6PD deficiency 1

Immunocompromised Patients

• Patients with diabetes or immunosuppression require a lower threshold for systemic antibiotics and hospital admission if extensive disease or systemic signs are present 1

Treatment Failure and Mupirocin Resistance

If impetigo fails to improve after 48-72 hours of topical mupirocin, switch to oral antibiotics (dicloxacillin, cephalexin, or amoxicillin-clavulanate for MSSA; clindamycin or TMP-SMX for MRSA). 3

• Consider mupirocin resistance, especially in high MRSA prevalence areas 3
• Obtain bacterial cultures if treatment failure occurs or MRSA is suspected 3
• For recurrent impetigo, implement decolonization strategies for S. aureus carriers 3

Infection Control Measures

Concurrent hygiene interventions are mandatory alongside antimicrobial therapy to prevent spread and recurrence: 1

• Keep draining lesions covered with clean, dry dressings 1
• Perform regular hand hygiene with soap and water or alcohol-based hand rubs 1
• Do not share personal items that contact skin (razors, towels, linens) 1
• Clean high-touch surfaces (counters, doorknobs, bathtubs) that may contact bare skin 1

Critical Pitfalls to Avoid

• Never prescribe oral antibiotics for limited impetigo when topical mupirocin is appropriate and more effective 1
• Never use cephalexin or other beta-lactams when MRSA is documented or strongly suspected 4, 1
• Never shorten oral therapy to less than 7 days, as shorter courses increase failure and recurrence risk 1
• Never use amoxicillin alone, as it lacks adequate S. aureus coverage 1
• Never assume beta-lactams provide MRSA coverage in regions with high community-acquired MRSA prevalence 1
• Never use disinfectant solutions as primary therapy, as there is little evidence they improve outcomes 1