What is the next step for a patient with impetigo (bacterial skin infection) who has not completely resolved after 5 days of azithromycin (antibiotic) treatment?

Switch to Oral Antibiotics for Treatment Failure

After 5 days of azithromycin without complete resolution of impetigo, you should switch to a different oral antibiotic—specifically cephalexin, dicloxacillin, or clindamycin—rather than repeating azithromycin. 1, 2

Why Not Repeat Azithromycin

• Azithromycin is not a first-line agent for impetigo and lacks robust evidence for this indication, with most guidelines recommending it only for specific conditions like cat scratch disease or chlamydia 3
• Treatment failure after 5 days suggests either inadequate coverage or resistant organisms, making repetition of the same antibiotic illogical 1, 2
• Azithromycin has increasing resistance rates among skin pathogens, particularly Staphylococcus aureus, which is the primary causative organism in impetigo 3, 2

Recommended Next Steps

First: Assess Disease Extent and MRSA Risk

• Obtain cultures from the lesions if not already done, as treatment failure warrants identification of the causative organism and antibiotic susceptibilities 1, 2
• Consider MRSA infection, especially in areas with high community MRSA prevalence or if the patient has risk factors 1, 2

Second: Choose Appropriate Oral Antibiotic

For presumed methicillin-susceptible S. aureus (MSSA):

• Cephalexin 250-500 mg four times daily for adults (25 mg/kg/day in 4 divided doses for children) for 7-10 days 1, 2
• Dicloxacillin 250 mg four times daily for adults (12 mg/kg/day in 4 divided doses for children) for 7-10 days 1, 2
• Amoxicillin-clavulanate 875/125 mg twice daily for adults (25 mg/kg/day of amoxicillin component in 2 divided doses for children) for 7-10 days 2

For suspected or confirmed MRSA:

• Clindamycin 300-450 mg three times daily for adults (10-20 mg/kg/day in 3 divided doses for children) for 7-10 days 1, 2
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily for adults (8-12 mg/kg/day based on trimethoprim component in 2 divided doses for children) for 7-10 days 2
• Doxycycline 100 mg twice daily (avoid in children under 8 years) for 7-10 days 2

Critical Pitfalls to Avoid

• Do not use penicillin alone, as it lacks adequate coverage against S. aureus, the primary pathogen in impetigo 1, 2
• Avoid macrolides (including azithromycin and erythromycin) due to increasing resistance rates and inferior efficacy compared to other options 2, 4, 5
• Do not assume topical therapy will work at this point—treatment failure after 5 days of oral antibiotics indicates need for systemic therapy with better anti-staphylococcal coverage 1, 2

When to Reassess

• If no improvement occurs within 48-72 hours of starting the new antibiotic, consider deeper infection, antibiotic resistance, or alternative diagnosis 1, 2
• Culture results should guide further therapy if the initial empiric choice fails 1, 2
• Consider hospitalization with IV antibiotics (such as vancomycin for MRSA) if oral therapy continues to fail 2

Special Considerations

• For pregnant patients, cephalexin is generally safe; avoid tetracyclines and trimethoprim-sulfamethoxazole near term 2
• For children under 8 years, avoid doxycycline and other tetracyclines due to risk of tooth staining 1, 2
• If cephalosporin allergy with type 1 hypersensitivity (anaphylaxis/hives), use clindamycin instead 1