What is the recommended treatment for a patient with a known allergy to amoxicillin (a beta-lactam antibiotic) who has a skin infection, such as cellulitis or abscesses?

Treatment of Skin Infections in Patients with Amoxicillin Allergy

For patients with known amoxicillin allergy presenting with cellulitis or skin abscesses, use cephalexin (a first-generation cephalosporin) as first-line therapy if the allergy history suggests a non-severe reaction; reserve macrolides (azithromycin or clarithromycin) or clindamycin for patients with documented severe/Type I hypersensitivity reactions. 1

Treatment Algorithm Based on Allergy Severity

For Non-Severe Historical Reactions (rash, mild urticaria without systemic symptoms):

• First-line: Cephalexin 500 mg four times daily for 10 days 1

  • Cross-reactivity between penicillins and first-generation cephalosporins is extremely low (likely no higher than cross-reactivity with unrelated antibiotic classes) 2
  • Cephalosporins can be safely used in patients with penicillin allergy, particularly when the reaction was not severe 3, 2

• Alternative: TMP-SMX (160-800 mg twice daily) or doxycycline (100 mg twice daily) for 10 days 1

  • Note: Adding TMP-SMX to cephalexin for non-purulent cellulitis provides no additional benefit 4

For Severe/Type I Hypersensitivity Reactions (anaphylaxis, angioedema, severe urticaria):

• Avoid all beta-lactams entirely 1

• First-line alternatives:

  • Azithromycin (for serious penicillin allergy) 1

  • Clindamycin 300 mg three times daily 1

    • Excellent activity against staphylococci, streptococci, and anaerobes (~90% of S. pneumoniae isolates) 1
    • Misses Pasteurella multocida (relevant for animal bites) 1

  • Doxycycline 100 mg twice daily 1

  • TMP-SMX 160-800 mg twice daily 1

For Purulent Skin Infections/Abscesses:

• Incision and drainage is the primary treatment 4
• If antibiotics needed and beta-lactam allergic:
  • TMP-SMX or doxycycline targeting CA-MRSA 4
  • Clindamycin if local resistance patterns permit 1

Critical Considerations for Allergy Assessment

Most "penicillin allergies" are not true allergies:

• Only ~1% of patients with reported penicillin allergy have clinically significant IgE-mediated reactions upon rechallenge 3
• ~8% of healthcare patients report penicillin allergy, but most are not confirmed 3

When to consider the allergy label invalid (can use beta-lactams):

• Reaction occurred in remote childhood (>5 years ago) and was non-severe 1
• Patient cannot recall details of the reaction 1
• Symptoms incompatible with allergy (GI complaints only, palpitations) 1
• Drug used successfully since the index reaction 1

Penicillin skin testing considerations:

• Not required before direct amoxicillin challenge in pediatric patients with benign cutaneous reactions 1
• For adults with distant (>5 years) benign reactions, direct challenge can be considered 1
• Resensitization after treatment is rare, even with repeated courses 1

Special Circumstances

Necrotizing Infections:

• Severe group A streptococcal infections: Clindamycin PLUS penicillin 1
• If beta-lactam allergic with necrotizing infection: Clindamycin remains essential 1
• Requires urgent surgical intervention regardless of antibiotic choice 1

Animal/Human Bites (if applicable):

• Avoid cephalexin, erythromycin, and clindamycin (poor Pasteurella coverage) 1
• For severe beta-lactam allergy: Fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) PLUS metronidazole 1
• Alternative: Doxycycline 100 mg twice daily 1

Common Pitfalls to Avoid

• Do not use macrolides or TMP-SMX as first-line if cephalosporins are safe options - bacterial failure rates of 20-25% possible 1
• Do not assume all beta-lactams are contraindicated - cross-reactivity is minimal, especially with non-severe historical reactions 3, 2
• Do not add TMP-SMX to cephalexin for routine cellulitis - no proven benefit 4
• Do not rely on aspiration cultures for cellulitis - unhelpful in 75-80% of cases 1

When Formal Allergy Testing is Indicated

• Suspected severe immediate-type reaction regardless of timing 1
• Suspected non-severe immediate reaction that occurred <5 years ago 1
• When the preferred antibiotic is vital and no acceptable alternatives exist 1

If life-threatening infection requires beta-lactam and patient has confirmed allergy, desensitization protocols exist and are relatively safe (30% develop mild cutaneous reactions during therapy) 5