Treatment of Strep Throat
First-Line Treatment: Penicillin or Amoxicillin
For patients without penicillin allergy, amoxicillin or penicillin V for 10 days is the definitive treatment of choice for strep throat, with amoxicillin preferred due to better palatability and once or twice-daily dosing that improves adherence. 1, 2
Recommended Dosing Regimens
Adults:
- Amoxicillin 500 mg orally twice daily for 10 days 1, 2
- Alternative: Penicillin V 500 mg orally twice daily for 10 days 1
Pediatric patients (≥3 months and <40 kg):
- Amoxicillin 50 mg/kg once daily (maximum 1,000 mg) OR 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1, 2
- Alternative: Penicillin V 250 mg two or three times daily for 10 days 1
Pediatric patients (<3 months):
- Amoxicillin 30 mg/kg/day divided every 12 hours for 10 days 2
Why These Are First-Line
Penicillin and amoxicillin remain the gold standard due to proven efficacy, narrow spectrum of activity, safety profile, low cost, and zero documented resistance of Group A Streptococcus worldwide 1. Amoxicillin is preferred over penicillin V in younger children due to superior palatability and availability as suspension 3. The twice-daily dosing of amoxicillin improves compliance compared to penicillin V's three or four times daily regimen 1, 4, 5.
Critical Treatment Duration
The full 10-day course is absolutely essential to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever, even if symptoms resolve in 3-4 days. 1, 2 Shortening the course by even a few days dramatically increases treatment failure rates and rheumatic fever risk 6, 7. Historical data from the 1950s-1970s established that 10 days of treatment consistently produces the highest cure rates 8.
Alternative Treatment for Penicillin-Allergic Patients
Step 1: Determine Type of Allergic Reaction
The type of penicillin allergy fundamentally changes management 6:
Non-immediate/non-anaphylactic reactions (delayed rash, mild symptoms):
- Cross-reactivity risk with cephalosporins is only 0.1% 6
- First-generation cephalosporins are safe and preferred 6
Immediate/anaphylactic reactions (anaphylaxis, angioedema, respiratory distress, urticaria within 1 hour):
- Cross-reactivity risk with cephalosporins is up to 10% 6
- Must avoid ALL beta-lactam antibiotics including cephalosporins 6
Step 2: Select Appropriate Alternative Based on Allergy Type
For non-immediate penicillin allergy (PREFERRED OPTION):
- Cephalexin 500 mg orally twice daily for 10 days (adults) 6
- Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days (children) 3, 6
- Alternative: Cefadroxil 1 gram once daily for 10 days (adults) or 30 mg/kg once daily (maximum 1 gram) for 10 days (children) 3, 6
First-generation cephalosporins have strong, high-quality evidence supporting their efficacy, with narrow spectrum activity, proven effectiveness, and low cost 6. They are the preferred first-line alternatives for non-anaphylactic penicillin allergy 6.
For immediate/anaphylactic penicillin allergy:
- Clindamycin 300 mg orally three times daily for 10 days (adults) 6
- Clindamycin 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days (children) 3, 6
Clindamycin is the preferred choice for immediate/anaphylactic penicillin allergy due to strong, moderate-quality evidence, high efficacy even in chronic carriers, and extremely low resistance of approximately 1% among Group A Streptococcus in the United States 6.
Alternative macrolides (less preferred due to resistance concerns):
- Azithromycin 500 mg once daily for 5 days (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days (children) 3, 6, 9
- Clarithromycin 250 mg twice daily for 10 days (adults) or 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days (children) 3, 6
Macrolides have strong, moderate-quality evidence but carry significant concerns about resistance, with 5-8% macrolide resistance rates in the United States that vary geographically 6. Azithromycin is the only antibiotic requiring just 5 days due to its prolonged tissue half-life 6, 9.
Critical Considerations and Common Pitfalls
Treatment Duration Errors
Never prescribe shorter courses than 10 days (except azithromycin's 5-day regimen). 6, 1 Even though symptoms typically resolve within 3-4 days without treatment, full course completion is essential for preventing acute rheumatic fever and suppurative complications 3, 1. Studies from the 1980s demonstrated that 5-day courses result in 27% recurrence rates compared to only 3-6% with 10-day courses 7.
Cephalosporin Use in Penicillin Allergy
Do not use cephalosporins if the patient had anaphylaxis, angioedema, or immediate urticaria to penicillin due to the 10% cross-reactivity risk 6. However, do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them 3.
Macrolide Resistance
Be aware of local macrolide resistance patterns before prescribing azithromycin or clarithromycin, as resistance varies geographically and can be much higher than the national average of 5-8% in some areas 6. Clindamycin is more reliable than macrolides when beta-lactams cannot be used, with only 1% resistance 6.
Avoiding Inappropriate Antibiotics
Never use trimethoprim-sulfamethoxazole (Bactrim) for strep throat due to high resistance rates (50%) and lack of efficacy against Group A Streptococcus 3. 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 6.
Adjunctive Symptomatic Treatment
Acetaminophen or NSAIDs (such as ibuprofen) should be offered for moderate to severe symptoms or high fever. 3, 6, 1 Aspirin must be avoided in children due to Reye syndrome risk 3, 6, 1. Corticosteroids are not recommended for routine use 3, 6.
Special Clinical Situations
When Oral Compliance is Questionable
Intramuscular benzathine penicillin G (single dose) is preferred for patients unlikely to complete a full 10-day oral course. 1 Dosing: 600,000 units for patients <27 kg (60 lb) and 1,200,000 units for patients ≥27 kg 1. This remains the gold standard in areas where rheumatic fever is still prevalent, particularly in poor and crowded inner-city populations where medical care is episodic and follow-up may be lacking 8.
Treatment Failures and Chronic Carriers
For patients who have failed both amoxicillin and azithromycin, clindamycin 300 mg orally three times daily for 10 days is the antibiotic of choice, as it demonstrates superior eradication rates in treatment failures and chronic carriers 6. Alternative regimens include amoxicillin-clavulanate (40 mg amoxicillin/kg/day in 3 doses for 10 days) or penicillin plus rifampin 6.
Consider whether the patient is experiencing true recurrent infections or is a chronic carrier with viral infections 3. Chronic carriers generally do not require treatment unless special circumstances exist, such as community outbreak of rheumatic fever, family history of rheumatic fever, or excessive family anxiety 6.
Diagnostic Confirmation
Every suspected episode of streptococcal pharyngitis must be confirmed with a rapid antigen detection test (RADT) or throat culture before treating with antibiotics 3, 1. A positive RADT is diagnostic and does not require backup culture 3. Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 6, 1.