What is the recommended treatment for Group A Streptococcal (GAS) infections in adults?

Treatment of Group A Streptococcal (GAS) Infections in Adults

Penicillin or amoxicillin for 10 days is the treatment of choice for GAS pharyngitis in adults, based on proven efficacy in preventing rheumatic fever, narrow spectrum, excellent safety profile, and low cost. 1

First-Line Treatment for Non-Allergic Patients

• Penicillin V 500 mg orally twice daily (or 250 mg three to four times daily) for 10 days is the preferred oral regimen, with strong, high-quality evidence supporting its use 1
• Amoxicillin 500 mg twice daily for 10 days is equally effective and often substituted for penicillin V due to better palatability 1
• Intramuscular benzathine penicillin G 1.2 million units as a single dose is the only regimen proven in controlled trials to prevent rheumatic fever and eliminates compliance concerns 1

The full 10-day course is essential—therapy can be safely delayed up to 9 days after symptom onset and still prevent rheumatic fever, but shortening the course below 10 days dramatically increases treatment failure rates and complication risk 1, 2

Treatment Algorithm for Penicillin-Allergic Patients

Non-Immediate (Non-Anaphylactic) Penicillin Allergy

First-generation cephalosporins are the preferred alternative with strong, high-quality evidence, as cross-reactivity risk is only 0.1% in patients with non-severe, delayed reactions 2

• Cephalexin 500 mg orally twice daily for 10 days (adults) 2
• Cefadroxil 1 gram orally once daily for 10 days is an acceptable alternative 2

Immediate/Anaphylactic Penicillin Allergy

All beta-lactam antibiotics must be avoided due to up to 10% cross-reactivity risk with cephalosporins in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, urticaria within 1 hour) 1, 2

Clindamycin is the preferred choice with strong, moderate-quality evidence:

• Clindamycin 300 mg orally three times daily for 10 days (adults) 1, 2
• Clindamycin has only ~1% resistance among GAS in the United States and demonstrates superior eradication rates even in chronic carriers 1, 2

Macrolide alternatives (strong, moderate-quality evidence):

• Azithromycin 500 mg orally once daily for 5 days—the only antibiotic requiring just 5 days due to prolonged tissue half-life 1, 2
• Clarithromycin 250 mg orally twice daily for 10 days 1, 2

Critical caveat: Macrolide resistance is 5-8% in the United States and varies geographically, making clindamycin more reliable when beta-lactams cannot be used 1, 2

Treatment of Invasive GAS Infections

Severe Invasive Infections (Necrotizing Fasciitis, Toxic Shock Syndrome)

Penicillin G 2-4 million units IV every 4 hours PLUS clindamycin 600-900 mg IV every 8 hours is essential, as clindamycin suppresses toxin production and maintains efficacy during high bacterial inocula 2, 3, 4

• Urgent surgical debridement is mandatory and must not be delayed—antibiotics alone are insufficient 3
• Duration: Continue until clinical improvement, typically 10-14 days minimum 3, 4

GAS Bacteremia

• High-dose penicillin G 12-24 million units/day IV in divided doses is first-line for serious infections 4
• For penicillin-allergic patients: Clindamycin 600-900 mg IV every 8 hours 3
• Duration: Minimum 10 days for uncomplicated infections; 4-6 weeks for endocarditis or deep-seated infections 3, 4
• Oral step-down therapy after 5 days of IV treatment is safe and effective for uncomplicated cases with similar mortality and readmission rates compared to definitive IV therapy 5

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (ibuprofen) should be offered for moderate to severe symptoms or high fever control 1, 2, 6
• Aspirin must be avoided in children due to Reye syndrome risk 1, 2, 6
• Corticosteroids are not recommended as adjunctive therapy 1, 2

Common Pitfalls to Avoid

• Do not prescribe shorter courses than 10 days (except azithromycin's 5-day regimen)—even a few days' reduction results in appreciable increases in treatment failure and rheumatic fever risk 1, 2
• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions—the 10% cross-reactivity risk makes all beta-lactams unsafe in this population 1, 2
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for GAS pharyngitis—sulfonamides do not eradicate GAS and are absolutely contraindicated 2
• Do not prescribe broad-spectrum cephalosporins (cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate—they are more expensive and select for resistant flora 2
• Do not delay surgical consultation when necrotizing infection is suspected—antibiotics alone are insufficient and delay increases mortality 3

Special Considerations

Recurrent GAS Pharyngitis or Treatment Failures

• Consider that the patient may be a chronic GAS carrier experiencing repeated viral infections rather than true recurrent streptococcal infections 1, 2
• Clindamycin 300 mg orally three times daily for 10 days demonstrates substantially higher eradication rates than penicillin in chronic carriers and treatment failures 2
• Alternative regimens: Amoxicillin-clavulanate 875 mg twice daily for 10 days or penicillin V plus rifampin for the last 4 days 2
• Chronic carriers generally do not require treatment unless special circumstances exist (community outbreak, family history of rheumatic fever) 1, 2

Post-Treatment Testing

• Routine follow-up throat cultures or rapid antigen tests are not recommended for asymptomatic patients who completed therapy 1, 2
• Testing should only be considered in special circumstances such as history of rheumatic fever 2