What are the first and second line treatments for a patient with streptococcal (Group A beta-hemolytic streptococcal) pharyngitis, considering potential penicillin allergy?

Treatment of Streptococcal Pharyngitis

Penicillin V (250 mg four times daily OR 500 mg twice daily) or amoxicillin (50 mg/kg once daily, maximum 1000 mg) for 10 days is first-line treatment, with penicillin preferred due to its narrow spectrum, proven efficacy, safety profile, and low cost. 1, 2

First-Line Treatment Options

For patients without penicillin allergy:

• Penicillin V is the drug of choice with two acceptable dosing regimens: 250 mg four times daily OR 500 mg twice daily for 10 days in adolescents and adults 1, 3
• Amoxicillin 50 mg/kg once daily (maximum 1000 mg) for 10 days is equally effective and often preferred in children due to better palatability and once-daily dosing 1, 2
• Intramuscular benzathine penicillin G as a single dose (600,000 units if <27 kg; 1,200,000 units if ≥27 kg) ensures compliance when adherence to oral therapy is uncertain 1, 2

Critical point: The full 10-day course is essential for all antibiotics except azithromycin to achieve maximal pharyngeal eradication and prevent acute rheumatic fever 1, 4, 2. Shorter courses of penicillin have not been adequately validated and increase the risk of treatment failure and rheumatic fever 1, 5.

Second-Line Treatment (Penicillin-Allergic Patients)

The choice of alternative depends on the type of penicillin allergy:

For Non-Immediate (Non-Anaphylactic) Penicillin Allergy:

First-generation cephalosporins are the preferred alternatives with strong, high-quality evidence 1, 4, 2:

• Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 1, 4
• Cefadroxil 30 mg/kg once daily (maximum 1 gram) for 10 days 4

The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions 4.

For Immediate/Anaphylactic Penicillin Allergy:

Patients with immediate hypersensitivity (anaphylaxis, urticaria, angioedema within 1 hour) must avoid ALL beta-lactam antibiotics including cephalosporins due to up to 10% cross-reactivity risk 1, 4.

Preferred alternatives:

• Clindamycin 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days is the preferred choice with approximately 1% resistance rate in the United States 1, 4, 2
• Azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days is acceptable but has 5-8% macrolide resistance in the United States 1, 4, 6
• Clarithromycin 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days is also acceptable with similar resistance concerns as azithromycin 4

Important Caveats and Pitfalls

Avoid these common errors:

• Do NOT use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk 4
• Do NOT shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen) as this dramatically increases treatment failure and rheumatic fever risk 1, 4, 2
• Do NOT prescribe broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate, as they are more expensive and more likely to select for antibiotic-resistant flora 4
• Be aware of local macrolide resistance patterns before prescribing azithromycin or clarithromycin, as resistance varies geographically and can be much higher than 5-8% in some areas 4, 2

Adjunctive Therapy

• Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever 1, 4, 2
• Aspirin must be avoided in children due to risk of Reye syndrome 1, 4, 2
• Corticosteroids are NOT recommended as adjunctive therapy 4

Special Considerations

Chronic carriers (asymptomatic patients with persistently positive cultures) generally do not require antimicrobial therapy, as they are unlikely to spread infection or develop complications 4, 2. If treatment is indicated for chronic carriers or treatment failures, clindamycin is particularly effective due to its ability to eradicate the organism 4, 2.

Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 4. Testing should only be considered in special circumstances, such as patients with a history of rheumatic fever 4.