What are alternative treatments for strep (streptococcal) infection in children allergic to amoxicillin?

Alternative Treatments for Strep Throat in Children with Amoxicillin Allergy

For children with penicillin/amoxicillin allergy and Group A streptococcal pharyngitis, first-generation cephalosporins (cephalexin or cefadroxil) are the preferred alternatives for non-severe allergies, while clindamycin is recommended for children with type I hypersensitivity reactions. 1, 2

Determining Allergy Severity

The type of allergic reaction dictates the appropriate alternative antibiotic:

• Non-severe/non-anaphylactic reactions: History of rash, mild gastrointestinal symptoms, or uncertain reactions without respiratory compromise or angioedema 1
• Type I hypersensitivity/severe reactions: History of anaphylaxis, angioedema, urticaria, bronchospasm, or other immediate-type reactions requiring avoidance of all beta-lactam antibiotics 3, 2

First-Line Alternatives for Non-Severe Penicillin Allergy

First-generation cephalosporins are the preferred alternatives when the allergy history does not suggest anaphylaxis:

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 1, 2
• Cefadroxil: 30 mg/kg once daily (maximum 1 g) for 10 days 1, 2

These agents have strong evidence supporting their efficacy and maintain the 10-day treatment duration necessary to prevent rheumatic fever. 1, 2

Important Caveat

Cross-reactivity between penicillins and cephalosporins is low (approximately 1-3%), but cephalosporins should be administered under medical supervision in children with uncertain allergy histories. 1 Avoid cephalosporins entirely in children with documented type I hypersensitivity to penicillins. 3, 2

Alternatives for Type I Hypersensitivity (Severe Allergy)

When beta-lactam antibiotics must be completely avoided:

• Clindamycin (preferred): 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 1, 2

  • Excellent streptococcal coverage with no cross-reactivity to penicillins 1
  • Requires susceptibility testing, though resistance remains uncommon 1

• Azithromycin (second-line): 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 2, 4

  • Critical limitation: Use only when local resistance patterns are favorable 1, 2
  • The higher dose (12 mg/kg/day for 5 days, total 60 mg/kg) is essential—lower doses have unacceptably high failure rates 5, 6
  • Bacteriologic eradication rates are inferior to penicillin, particularly with the older 10 mg/kg/day for 3 days regimen (65% vs. 82% eradication) 6
  • Increasing macrolide resistance makes this a less reliable option in many communities 1, 7

• Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 1, 2

  • Similar resistance concerns as azithromycin 7
  • In areas with >25% clarithromycin resistance, eradication rates drop dramatically (14-19% for resistant strains) 7

Treatment Duration and Compliance

All oral regimens must be completed for the full prescribed duration to prevent acute rheumatic fever, regardless of symptom resolution: 1, 3, 2

• 10-day courses: Cephalexin, cefadroxil, clindamycin, clarithromycin 1, 2
• 5-day course: Azithromycin only (at 12 mg/kg/day dosing) 1, 2, 5

Alternative for Compliance Concerns

Benzathine penicillin G intramuscularly can be considered if compliance with oral therapy is doubtful, though this requires confirming the allergy is not to penicillin itself: 2

• <27 kg: 600,000 units as single dose
• ≥27 kg: 1,200,000 units as single dose

Common Pitfalls to Avoid

• Do not use macrolides (azithromycin/clarithromycin) as first-line alternatives when cephalosporins or clindamycin are options, due to increasing resistance rates 1, 2, 7
• Do not use the older azithromycin regimen of 10 mg/kg/day for 3 days—this has inferior eradication rates; use 12 mg/kg/day for 5 days if azithromycin is chosen 5, 6
• Do not prescribe shorter courses than recommended (e.g., 5 days of cephalosporins)—only azithromycin at the higher dose has evidence for shortened therapy 1, 2
• Do not use sulfonamides or tetracyclines for streptococcal pharyngitis due to high resistance rates and poor eradication 3
• Assess clinical response at 48-72 hours and consider local resistance patterns, particularly for macrolides 2

Special Considerations

For children with uncertain or mild allergy history (e.g., distant rash), options include: 1

• Trial of amoxicillin under medical observation
• Oral cephalosporin with substantial pneumococcal activity (cefpodoxime, cefprozil, cefuroxime) under medical supervision
• Direct use of clindamycin or levofloxacin (in growth-mature children)

Susceptibility testing should be performed when using clindamycin or macrolides to confirm the isolate is susceptible, given variable resistance patterns. 1, 4