What is the recommended work‑up and antibiotic regimen for suspected Group A streptococcal pharyngitis, including alternatives for penicillin‑allergic patients?

Work-Up and Antibiotic Regimen for Group A Streptococcal Pharyngitis

Diagnostic Confirmation Before Treatment

Laboratory confirmation with either a rapid antigen detection test (RADT) or throat culture is mandatory before prescribing antibiotics, because clinical features alone cannot reliably distinguish bacterial from viral pharyngitis. 1, 2

Age-Specific Testing Algorithms

• Children and adolescents (ages 5–15): Perform RADT first; if negative, obtain a backup throat culture because RADT sensitivity is only 80–90%, missing 10–20% of true infections. 1, 2
• Adults: A negative RADT alone is sufficient to rule out Group A Streptococcus; no backup culture is needed given the 5–10% prevalence and extremely low risk of acute rheumatic fever. 1, 2
• Children under 3 years: Do not test routinely, as streptococcal pharyngitis and acute rheumatic fever are rare in this age group, except when an older sibling has confirmed infection. 1, 2

When NOT to Test

• Do not test when viral features are present: cough, rhinorrhea, hoarseness, conjunctivitis, or oral ulcers strongly indicate viral etiology. 1, 2
• Test only when bacterial features predominate: sudden-onset sore throat, fever, tonsillar exudates, tender anterior cervical lymphadenopathy, and absence of viral signs. 1, 2, 3

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First-Line Antibiotic Therapy (Non-Allergic Patients)

Penicillin V or amoxicillin for a full 10 days is the definitive first-line regimen, offering proven efficacy in preventing acute rheumatic fever, zero documented resistance worldwide, narrow spectrum, excellent safety, and low cost. 1, 4, 3

Specific Dosing Regimens

Population	Drug & Dose	Duration
Adults	Penicillin V 500 mg orally twice daily	10 days
Children ≥27 kg	Penicillin V 500 mg orally twice daily	10 days
Children <27 kg	Penicillin V 250 mg orally 2–3 times daily	10 days
All ages	Amoxicillin 50 mg/kg once daily (max 1000 mg) or 25 mg/kg twice daily (max 500 mg/dose)	10 days

1, 4, 5

Intramuscular Option for Adherence Concerns

• Benzathine penicillin G: Single IM dose of 600,000 units (<27 kg) or 1.2 million units (≥27 kg) guarantees complete treatment when oral adherence is doubtful. 1, 4

Critical Treatment Duration

A complete 10-day course is mandatory to achieve maximal pharyngeal eradication and prevent acute rheumatic fever; shortening the course by even 2–3 days markedly increases treatment failure and rheumatic fever risk. 1, 4, 6

• Therapy initiated within 9 days of symptom onset still effectively prevents acute rheumatic fever. 1, 2
• The primary goal is prevention of acute rheumatic fever and suppurative complications, not merely symptom relief. 1, 3, 7

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Alternatives for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

First-generation cephalosporins are the preferred alternatives, with strong, high-quality evidence and only ~0.1% cross-reactivity risk in patients with delayed, mild penicillin reactions. 1, 4

Drug	Adult Dose	Pediatric Dose	Duration
Cephalexin	500 mg orally twice daily	20 mg/kg twice daily (max 500 mg/dose)	10 days
Cefadroxil	1 g orally once daily	30 mg/kg once daily (max 1 g)	10 days

1, 4

Immediate/Anaphylactic Penicillin Allergy

All β-lactam antibiotics (including cephalosporins) must be avoided because cross-reactivity can reach 10% in patients with immediate hypersensitivity reactions such as anaphylaxis, angioedema, or urticaria within 1 hour of exposure. 1, 4

Preferred Non-β-Lactam Alternative

Clindamycin is the optimal choice, with only ~1% resistance among U.S. Group A Streptococcus isolates and superior eradication rates even in chronic carriers. 1, 4

Drug	Adult Dose	Pediatric Dose	Duration
Clindamycin	300 mg orally three times daily	7 mg/kg three times daily (max 300 mg/dose)	10 days

1, 4

Macrolide Alternatives (Less Preferred)

• Azithromycin: 500 mg once daily for 5 days (adults) or 12 mg/kg once daily (max 500 mg) for 5 days (children); the only antibiotic requiring just 5 days due to prolonged tissue half-life. 1, 4, 8
• Clarithromycin: 250 mg twice daily for 10 days (adults) or 7.5 mg/kg twice daily (max 250 mg/dose) for 10 days (children). 1, 4
• Macrolide resistance in the United States ranges from 5–8% and varies geographically, making clindamycin more reliable when β-lactams cannot be used. 1, 4, 8

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Management of Treatment Failure or Recurrent Infection

If initial therapy with penicillin or amoxicillin fails despite confirmed compliance, switch to clindamycin or amoxicillin-clavulanate, which achieve substantially higher eradication rates in chronic carriers and persistent infections. 1, 4

Alternative Regimens for Documented Failure

Regimen	Dosing	Duration
Clindamycin	20–30 mg/kg/day divided three times daily (max 300 mg/dose)	10 days
Amoxicillin-clavulanate	40 mg amoxicillin/kg/day divided three times daily (max 2000 mg amoxicillin/day)	10 days
Penicillin V + rifampin	Penicillin V 50 mg/kg/day in four doses (max 2000 mg/day) × 10 days plus rifampin 20 mg/kg/day once daily for final 4 days (max 600 mg/day)	10 days total

1, 4

Distinguishing Chronic Carriage from True Recurrence

• Most patients with multiple culture-positive episodes are chronic carriers experiencing concurrent viral infections rather than true recurrent streptococcal infections. 1, 4
• Chronic carriers generally do not require treatment unless special circumstances exist (e.g., community outbreak of rheumatic fever, family history of rheumatic fever, or excessive family anxiety). 1, 4
• Routine post-treatment cultures are unnecessary for asymptomatic patients; positive results often reflect carrier status rather than treatment failure. 1, 2, 4

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Common Pitfalls to Avoid

• Do not prescribe antibiotics based solely on clinical appearance (e.g., tonsillar exudates or white patches), as these findings occur in both viral and bacterial infections. 1, 2
• Do not shorten the antibiotic course below 10 days (except azithromycin's 5-day regimen), as this dramatically increases treatment failure and rheumatic fever risk. 1, 4, 6
• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to ~10% cross-reactivity risk. 1, 4
• Do not test or treat asymptomatic household contacts; up to one-third may be carriers, and prophylactic treatment does not reduce subsequent infection rates. 1, 2
• Do not prescribe trimethoprim-sulfamethoxazole for strep throat; it fails to eradicate Group A Streptococcus in 20–25% of cases. 1, 4

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Adjunctive Symptomatic Management

• Offer acetaminophen or ibuprofen for moderate-to-severe sore throat, fever, or systemic discomfort. 1, 4
• Avoid aspirin in children due to the risk of Reye syndrome. 1, 2, 4
• Corticosteroids are not recommended as adjunctive therapy for streptococcal pharyngitis. 1, 2