Treatment of Streptococcal Pharyngitis in Penicillin-Allergic Patients
For patients with non-anaphylactic penicillin allergy, prescribe a first-generation cephalosporin (cephalexin 20 mg/kg/dose twice daily or cefadroxil 30 mg/kg once daily) for 10 days; for patients with immediate/anaphylactic penicillin allergy, prescribe clindamycin 7 mg/kg three times daily (maximum 300 mg/dose) for 10 days. 1, 2
Treatment Algorithm Based on Allergy Type
Non-Anaphylactic Penicillin Allergy (No History of Immediate Hypersensitivity)
First-line: First-generation cephalosporins for 10 days 1, 2
- Cephalexin: 20 mg/kg/dose twice daily (preferred narrow-spectrum option) 1, 3
- Cefadroxil: 30 mg/kg once daily (alternative narrow-spectrum option) 1, 3
These narrow-spectrum cephalosporins are strongly preferred over broad-spectrum agents (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) because they are less expensive and less likely to select for antibiotic-resistant flora 1. The evidence quality for first-generation cephalosporins is strong and high-quality 2.
Immediate/Anaphylactic Penicillin Allergy
First-line: Clindamycin for 10 days 1, 2
- Clindamycin: 7 mg/kg three times daily (maximum 300 mg/dose) for 10 days 1, 2
- Clindamycin resistance among Group A Streptococcus (GAS) isolates in the United States is approximately 1%, making this an excellent choice 1, 2
- Evidence quality is strong with moderate-quality data 2
Alternative: Macrolides 1
- Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 4
- Clarithromycin: 7.5 mg/kg twice daily (maximum 250 mg/dose) for 10 days 1, 3
- Erythromycin: 20-40 mg/kg/day divided 2-3 times daily for 10 days (associated with substantially higher gastrointestinal side effects) 1, 3
Critical Considerations and Pitfalls
Cross-Reactivity Warning
Up to 10% of patients with immediate hypersensitivity to penicillin may have cross-reactivity with cephalosporins, so these agents must be avoided in patients with anaphylactic-type reactions to penicillin. 1, 2 This is a critical safety consideration that cannot be overlooked.
Macrolide Resistance Concerns
Macrolide resistance rates among pharyngeal GAS isolates in the United States are approximately 5-8%, which can result in treatment failures 1. This resistance varies geographically and temporally, so local resistance patterns should inform prescribing decisions 3, 5. Despite this concern, macrolides remain reasonable alternatives when cephalosporins and clindamycin cannot be used 1.
Duration of Therapy
Most oral antibiotics require a full 10-day course to achieve maximal pharyngeal eradication of GAS 1, 2. The only exception is azithromycin, which requires only 5 days due to its prolonged tissue half-life 1, 4. Prescribing shorter courses than recommended (except for azithromycin) can lead to treatment failure and complications 3.
Agents to Avoid
The following agents should never be used for streptococcal pharyngitis 1:
- Tetracyclines: High prevalence of resistant strains 1
- Sulfonamides and trimethoprim-sulfamethoxazole: Do not eradicate GAS from patients with acute pharyngitis 1
- Older fluoroquinolones (ciprofloxacin): Limited activity against GAS 1
- Newer fluoroquinolones (levofloxacin, moxifloxacin): Unnecessarily broad spectrum and expensive 1
Adjunctive Therapy for Symptom Management
Acetaminophen or NSAIDs (such as ibuprofen) should be used for moderate to severe symptoms or high fever 1, 5. NSAIDs demonstrate superior efficacy in reducing fever and pain compared to placebo 5. Aspirin must be avoided in children due to the risk of Reye syndrome 1, 5.
Corticosteroids are not recommended as adjunctive therapy 1, 5.
Comparative Efficacy Notes
One study suggests that 10 days of clarithromycin may be more effective in eradicating GAS pharyngitis than 5 days of azithromycin 1. However, azithromycin's convenience of once-daily dosing for only 5 days may enhance adherence, which is a major cause of treatment failure with longer regimens 6.
Clindamycin demonstrates high efficacy in eradicating streptococci, even in chronic carriers, making it particularly valuable for recurrent infections 3.