What is the best antibiotic for strep throat?

Best Antibiotic for Strep Throat

Penicillin (penicillin V) or amoxicillin remains the best antibiotic for strep throat due to proven efficacy, safety, narrow spectrum, zero resistance development over five decades, and low cost. 1

First-Line Treatment Recommendations

For Non-Allergic Patients

Penicillin V is the drug of choice for adults and older children:

• Adults: 250 mg three to four times daily OR 500 mg twice daily for 10 days 1
• Children: 250 mg two to three times daily for 10 days 1

Amoxicillin is preferred for younger children:

• Dosing: 50 mg/kg once daily (maximum 1000 mg) for 10 days 2
• Preferred over penicillin V due to better taste acceptance and availability as suspension 1
• Important caveat: Avoid amoxicillin in older children and adolescents due to risk of severe rash if Epstein-Barr virus infection is present 1

Intramuscular benzathine penicillin G:

• Dosing: 1.2 million units as a single injection 1
• Preferred when compliance with 10-day oral therapy is unlikely 1, 2
• Historically the "gold standard" with highest cure rates 3

Why Penicillin Remains Superior

Group A beta-hemolytic streptococci have shown zero resistance to penicillin over five decades with no increase in minimum inhibitory concentrations 1. While newer antibiotics (cephalosporins, macrolides) may show statistically better eradication rates, these differences are not clinically relevant 1.

Alternative Antibiotics for Penicillin-Allergic Patients

For Non-Immediate (Non-Anaphylactic) Allergy

First-generation cephalosporins are first-line alternatives:

• Cephalexin: 20 mg/kg per dose twice daily for 10 days 4
• Cefadroxil: 30 mg/kg once daily for 10 days 4
• Strong, high-quality evidence for efficacy 4
• Critical caveat: Up to 10% cross-reactivity exists with immediate penicillin hypersensitivity, so avoid in anaphylactic allergy 4

For Immediate/Anaphylactic Penicillin Allergy

Clindamycin is the preferred alternative:

• Dosing: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 4, 2
• Strong, moderate-quality evidence 4
• Highly effective even in chronic carriers 4
• Resistance rate in the United States is approximately 1% 4

Macrolides are acceptable alternatives but with important limitations:

• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 4, 2, 5
• Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 4
• Erythromycin: 20-40 mg/kg/day divided 2-3 times daily for 10 days 4

Major concern with macrolides: Resistance rates among Group A Streptococcus vary geographically, with approximately 5-8% resistance in the United States 4, 2. In areas with high macrolide resistance, cephalexin is preferred over macrolides for severe penicillin allergy 4.

Evidence Comparing Antibiotics

Cephalosporins vs. Penicillin

While meta-analyses show cephalosporins have statistically better clinical cure rates (OR 2.29-2.34 favoring cephalosporins), the absolute differences are small and not clinically relevant 1. A Cochrane review found uncertain differences in symptom resolution between cephalosporins and penicillin 6.

Macrolides vs. Penicillin

Azithromycin showed clinical and microbiological superiority to penicillin V in three U.S. trials, with 95% bacteriologic eradication at Day 14 versus 73% for penicillin 5. However, approximately 1% of azithromycin-susceptible isolates became resistant following therapy 5. The Cochrane review found uncertain differences between macrolides and penicillin for symptom resolution 6.

Amoxicillin vs. Penicillin V

Higher-dose amoxicillin (40 mg/kg/day) demonstrated significantly better clinical cure (87.9% vs 70.9%, P=0.025) and bacteriologic cure (79.3% vs 54.5%, P=0.005) compared to standard-dose penicillin V 7. This suggests that inadequate penicillin dosing may explain perceived declining effectiveness 7.

Critical Clinical Considerations

Duration of Therapy

• Most antibiotics require a full 10-day course to achieve maximal pharyngeal eradication 4, 2
• Exception: Azithromycin requires only 5 days due to prolonged tissue half-life 4, 2
• Shorter courses risk treatment failure and complications 4

When to Treat

• Antibiotics should not be used in patients with 0-2 Centor criteria 1
• For patients with 3-4 Centor criteria, discuss modest benefits (1-2 days symptom reduction) versus risks of side effects, resistance, and costs 1
• Delayed prescribing (>48 hours after consultation) is a valid option with no difference in complication rates 1

Common Pitfalls to Avoid

• Using azithromycin or other macrolides as first-line when penicillin can be used contributes to antimicrobial resistance 2
• Assuming all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them 4
• Prescribing amoxicillin to adolescents without considering Epstein-Barr virus risk 1
• Failing to consider local macrolide resistance patterns when prescribing 4, 2

Post-Treatment Follow-Up

Routine post-treatment throat cultures are not recommended for asymptomatic patients who completed therapy 4, 2.