What are the best oral antibiotics for treating impetigo in a patient, considering factors such as age, weight, renal function, and potential allergy to penicillin?

Best Oral Antibiotics for Impetigo

Cephalexin is the first-line oral antibiotic for impetigo at 25-50 mg/kg/day divided into 4 doses (or 250-500 mg four times daily in adults) for 7 days, with clindamycin or trimethoprim-sulfamethoxazole reserved for suspected MRSA or penicillin allergy. 1

First-Line Oral Therapy for Presumed MSSA

The Infectious Diseases Society of America and American Academy of Pediatrics establish a clear hierarchy for oral antibiotics:

• Cephalexin is the preferred first-line agent at 25-50 mg/kg/day divided into 4 doses for children, or 250-500 mg four times daily for adults, for 7 days 1
• Dicloxacillin is an equally effective alternative at the same dosing (25-50 mg/kg/day divided into 4 doses for children, or 250 mg four times daily for adults) for 7 days 1, 2
• Both agents provide excellent coverage for methicillin-susceptible S. aureus, which is now the predominant causative organism 1

The evidence supporting cephalexin is particularly strong, with studies demonstrating that twice-daily dosing may enhance compliance while maintaining equal efficacy to dicloxacillin's four-times-daily regimen 3

When to Switch to MRSA-Covering Agents

In areas with high MRSA prevalence or when MRSA is suspected, empiric therapy must be adjusted:

• Clindamycin at 20-30 mg/kg/day divided into 3 doses for children (or 300-450 mg three to four times daily for adults) for 7 days 1, 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) at 8-12 mg/kg/day (based on trimethoprim component) divided into 2 doses for children (or 1-2 double-strength tablets twice daily for adults) for 7 days 1, 2
• Doxycycline at 2-4 mg/kg/day divided into 2 doses for 7 days, but only in children over 8 years old due to permanent dental staining risk 1

Penicillin Allergy Considerations

For patients reporting penicillin allergy, the approach depends on reaction type:

• Cephalexin remains safe except in patients with type 1 hypersensitivity reactions (anaphylaxis/hives) to β-lactams 1
• Clindamycin is the preferred alternative for true penicillin-allergic patients at 300-450 mg three to four times daily for adults, or 20-30 mg/kg/day in 3 divided doses for children 1, 2
• Macrolides (erythromycin) can be used but resistance rates are rising, making them less reliable 1

Co-Amoxiclav (Amoxicillin-Clavulanate) as an Alternative

The WHO and IDSA list co-amoxiclav as an acceptable oral option:

• Co-amoxiclav provides dual coverage for both S. aureus and S. pyogenes 1
• It is appropriate for extensive disease, outbreaks requiring decreased transmission, or when topical therapy has failed 1
• Standard 7-day duration applies 1

Critical Pitfalls to Avoid

• Never use penicillin or amoxicillin alone—the IDSA explicitly states these lack adequate coverage against S. aureus, which is now the predominant pathogen 1, 4
• Always treat for 7 days with oral antibiotics, not the shorter 5-day course used for topical agents 1, 2
• Avoid tetracyclines in children under 8 years due to permanent dental staining risk 1, 2
• Do not use topical disinfectants as primary therapy—there is little evidence they improve outcomes 1

When Oral Antibiotics Are Indicated Over Topical Therapy

Oral antibiotics should be used instead of topical mupirocin when:

• Numerous lesions are present (extensive disease) 1
• Lesions involve the face, eyelid, or mouth 2
• No improvement after 3-5 days of topical therapy 1, 2
• During outbreaks to decrease transmission 1, 2
• Systemic symptoms are present 2
• Patient is immunocompromised or has diabetes 1

Special Population Considerations

• Pregnant patients: Cephalexin is considered a safe alternative 1
• Immunocompromised patients: Lower threshold for oral antibiotics, monitor closely for treatment failure, and consider longer treatment duration based on clinical response 2
• During outbreaks of poststreptococcal glomerulonephritis: Systemic antimicrobials should be used to eliminate nephritogenic strains 1, 2

Treatment Algorithm Summary

1. Limited disease → Topical mupirocin 2% ointment twice daily for 5 days 1
2. Extensive disease or oral therapy needed → Cephalexin or dicloxacillin for 7 days 1
3. MRSA suspected or high prevalence area → Clindamycin or TMP-SMX for 7 days 1
4. Penicillin allergy (non-anaphylactic) → Cephalexin for 7 days 1
5. Penicillin allergy (anaphylactic) → Clindamycin for 7 days 1
6. No improvement by 3-5 days → Reassess for MRSA, obtain cultures, switch to MRSA-covering agent 2