What are the recommended diagnostic steps and antibiotic regimens for acute tonsillopharyngitis in non‑pregnant adults, children, and pregnant women?

Antibiotic Management of Acute Tonsillopharyngitis

Non-Pregnant Adults

For non-pregnant adults with confirmed Group A Streptococcal pharyngitis, prescribe penicillin V 500 mg orally twice daily or amoxicillin 500 mg orally twice daily for a mandatory 10-day course. 1

First-Line Therapy

• Penicillin V remains the drug of choice because of proven efficacy, zero documented resistance worldwide, narrow antimicrobial spectrum, excellent safety profile, and low cost. 1, 2
• Alternative dosing: Penicillin V 250 mg four times daily for 10 days is equally effective but twice-daily dosing improves adherence. 1, 3
• Amoxicillin 500 mg twice daily for 10 days is an acceptable alternative with identical efficacy. 1, 2
• For patients with uncertain adherence, a single intramuscular injection of benzathine penicillin G 1.2 million units guarantees compliance. 1, 3

Penicillin-Allergic Adults

Non-Immediate (Delayed) Reactions

• First-generation cephalosporins are preferred: cephalexin 500 mg orally twice daily for 10 days. 1, 2
• Cross-reactivity risk is only 0.1% in patients with delayed, mild penicillin reactions (rash occurring >1 hour after exposure). 1, 2
• Cefadroxil 1 g once daily for 10 days is an alternative with comparable efficacy. 2, 3

Immediate/Anaphylactic Reactions

• All β-lactam antibiotics must be avoided because cross-reactivity reaches 10% in patients with anaphylaxis, angioedema, or urticaria within 1 hour of penicillin exposure. 1, 2
• Clindamycin 300 mg orally three times daily for 10 days is the preferred choice, with only 1% resistance among U.S. Group A Streptococcus isolates and superior eradication even in chronic carriers. 1, 2
• Azithromycin 500 mg once daily for 5 days is acceptable but macrolide resistance ranges from 5-8% in the United States. 1, 2
• Clarithromycin 250 mg twice daily for 10 days is another macrolide option with similar resistance concerns. 1, 2

Critical Treatment Duration

• A full 10-day course is mandatory for all antibiotics (except azithromycin's 5-day regimen) to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 1
• Shortening the course by even 2-3 days markedly increases treatment failure rates and rheumatic fever risk, even when symptoms resolve within 3-4 days. 1, 2
• Azithromycin requires only 5 days because of its prolonged tissue half-life. 1, 2

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Children

For children with confirmed Group A Streptococcal pharyngitis, prescribe amoxicillin 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for a mandatory 10-day course. 1, 2

First-Line Therapy

• Amoxicillin is preferred over penicillin V in younger children because of better palatability and availability as a liquid suspension, while maintaining identical efficacy. 1, 2
• Penicillin V 250 mg twice or three times daily for 10 days (adjusted by weight) is equally effective. 1, 3
• For children with uncertain adherence, benzathine penicillin G as a single intramuscular injection: 600,000 units for weight <27 kg or 1.2 million units for weight ≥27 kg. 1, 3

Penicillin-Allergic Children

Non-Immediate (Delayed) Reactions

• Cephalexin 20 mg/kg twice daily (maximum 500 mg per dose) for 10 days is the preferred alternative. 1, 2
• Cross-reactivity risk is only 0.1% with delayed, mild penicillin reactions. 1, 2
• Cefadroxil 30 mg/kg once daily (maximum 1 g) for 10 days is an alternative. 2, 3

Immediate/Anaphylactic Reactions

• Clindamycin 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days is the preferred choice, with approximately 1% resistance and superior eradication in chronic carriers. 1, 2
• Azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days is acceptable but carries 5-8% macrolide resistance. 1, 2
• Clarithromycin 7.5 mg/kg twice daily (maximum 250 mg per dose) for 10 days is another option with similar resistance concerns. 1, 2

Diagnostic Confirmation Required

• Confirm Group A Streptococcus infection with rapid antigen detection test or throat culture before prescribing antibiotics, because clinical features alone cannot reliably differentiate bacterial from viral pharyngitis. 1
• A positive rapid antigen test is diagnostic and does not require backup culture. 1
• A negative rapid antigen test in children and adolescents should be followed by throat culture. 1
• Testing is generally not recommended for children younger than 3 years because acute rheumatic fever is rare and streptococcal pharyngitis uncommon in this age group. 1

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Pregnant Women

For pregnant women with confirmed Group A Streptococcal pharyngitis, prescribe penicillin V 500 mg orally twice daily or amoxicillin 500 mg orally twice daily for a mandatory 10-day course. 1, 3

First-Line Therapy

• Penicillin and amoxicillin are safe throughout pregnancy and remain the drugs of choice. 1, 3
• Benzathine penicillin G 1.2 million units intramuscularly as a single dose is an alternative for adherence concerns. 1, 3

Penicillin-Allergic Pregnant Women

Non-Immediate (Delayed) Reactions

• Cephalexin 500 mg orally twice daily for 10 days is the preferred alternative, with only 0.1% cross-reactivity risk in delayed reactions. 1, 2
• Cefadroxil 1 g once daily for 10 days is an alternative. 2, 3

Immediate/Anaphylactic Reactions

• Clindamycin 300 mg orally three times daily for 10 days is the preferred choice, with 1% resistance and excellent safety profile in pregnancy. 1, 2
• Azithromycin 500 mg once daily for 5 days is acceptable but carries 5-8% macrolide resistance. 1, 2

Special Consideration: Group B Streptococcus Prophylaxis

• For pregnant women requiring intrapartum antibiotic prophylaxis for Group B Streptococcus with non-anaphylactic penicillin allergy, cefazolin is recommended. 2
• For immediate/anaphylactic penicillin allergy, clindamycin or vancomycin should be used based on susceptibility testing. 2

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Adjunctive Symptomatic Management (All Populations)

• Acetaminophen or ibuprofen should be offered for moderate-to-severe sore throat, fever, or systemic discomfort. 1
• Aspirin must be avoided in children because of Reye syndrome risk. 1
• Corticosteroids are not recommended as adjunctive therapy for streptococcal pharyngitis. 1

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Common Pitfalls to Avoid

• Do not prescribe antibiotics without confirming diagnosis via rapid antigen test or throat culture, as most pharyngitis cases are viral. 1
• Do not shorten the antibiotic course below 10 days (except azithromycin's 5-day regimen), as this markedly increases treatment failure and rheumatic fever risk. 1, 2
• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions because of 10% cross-reactivity risk. 1, 2
• Do not prescribe trimethoprim-sulfamethoxazole for strep throat; it fails to eradicate Group A Streptococcus in 20-25% of cases. 2, 3
• Do not use tetracyclines or fluoroquinolones, which have high resistance rates and unnecessary broad-spectrum activity. 2, 3
• Do not order routine post-treatment throat cultures for asymptomatic patients who completed therapy; reserve testing for special circumstances such as history of rheumatic fever. 1

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Management of Treatment Failure

• If symptoms persist after a fully adhered 10-day course, switch to clindamycin (300 mg three times daily for 10 days in adults; 7 mg/kg three times daily for 10 days in children) to achieve higher eradication rates, especially in chronic carriers. 1, 2
• Amoxicillin-clavulanate 40 mg/kg/day divided three times daily (maximum 2000 mg amoxicillin/day) for 10 days is an alternative for chronic carriers or treatment failures. 2
• Consider that the patient may be a chronic carrier experiencing repeated viral infections rather than true treatment failure; chronic carriers generally do not require treatment unless special circumstances exist. 1