What is the recommended antibiotic regimen for an adult with confirmed Group A Streptococcus infection, including alternatives for penicillin allergy and invasive disease?

Treatment of Group A Streptococcal Infections in Adults

First-Line Treatment for Non-Allergic Patients

Penicillin V 500 mg orally twice daily (or 250 mg four times daily) for 10 days is the drug of choice for confirmed Group A Streptococcal pharyngitis in adults. 1

• Penicillin V remains first-line due to proven efficacy, narrow spectrum, excellent safety profile, low cost, and the complete absence of documented penicillin resistance in Group A Streptococcus worldwide 1
• Amoxicillin 500 mg twice daily for 10 days is an equally effective alternative with comparable efficacy 1
• The full 10-day course is mandatory to achieve maximal pharyngeal eradication and prevent acute rheumatic fever, even if symptoms resolve within 3-4 days 1
• For patients unlikely to complete oral therapy, intramuscular benzathine penicillin G 1.2 million units as a single dose is preferred 1

Treatment Algorithm for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

For adults with non-anaphylactic penicillin allergy (e.g., delayed rash), prescribe cephalexin 500 mg twice daily for 10 days or cefadroxil 1 gram once daily for 10 days. 1, 2

• First-generation cephalosporins carry only 0.1% cross-reactivity risk in patients with delayed, non-severe penicillin reactions 3
• These agents have strong, high-quality evidence supporting their use and are preferred over broader-spectrum alternatives 1, 2
• The full 10-day course is essential; shortening the regimen increases treatment failure rates and rheumatic fever risk 1

Immediate/Anaphylactic Penicillin Allergy

For adults with immediate hypersensitivity reactions to penicillin (anaphylaxis, angioedema, urticaria within 1 hour), prescribe clindamycin 300 mg orally three times daily for 10 days. 1, 3

• All beta-lactam antibiotics, including cephalosporins, must be avoided due to up to 10% cross-reactivity risk 1, 3
• Clindamycin has strong, moderate-quality evidence with only ~1% resistance among U.S. Group A Streptococcus isolates 1, 3
• Clindamycin demonstrates superior eradication rates in treatment failures and chronic carriers compared to penicillin 1, 3

Alternative macrolide options for immediate penicillin allergy:

• Azithromycin 500 mg on day 1, then 250 mg daily for days 2-5 (total 5 days) 1
• Clarithromycin 250 mg twice daily for 10 days 1
• Macrolide resistance ranges from 5-8% in the United States, making clindamycin more reliable 1, 3
• Azithromycin is the only antibiotic that can be shortened to 5 days due to its prolonged tissue half-life 1, 3

Treatment of Invasive Group A Streptococcal Disease

For necrotizing fasciitis or streptococcal toxic shock syndrome, prescribe penicillin 2-4 million units IV every 4-6 hours PLUS clindamycin 600-900 mg IV every 8 hours. 1, 4, 5

• Combination therapy with clindamycin plus penicillin has superior efficacy versus penicillin alone in severe invasive infections 1
• Clindamycin suppresses production of streptococcal pyrogenic exotoxins and modulates cytokine production 1
• Early surgical consultation is imperative for necrotizing fasciitis 5
• After clinical improvement, transition to oral penicillin VK 250-500 mg every 6 hours 1

Critical Pitfalls to Avoid

• Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk 1, 3
• Do not shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen), as this dramatically increases treatment failure and rheumatic fever risk 1, 3, 2
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for streptococcal pharyngitis, as it fails to eradicate Group A Streptococcus in 20-25% of cases 3
• Do not prescribe broad-spectrum cephalosporins (cefdinir, cefpodoxime, cefuroxime) when narrow-spectrum first-generation agents are appropriate, as they are more expensive and promote resistant flora 1
• 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, 3

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 1, 3
• Avoid aspirin in children due to Reye syndrome risk 1, 3
• Corticosteroids are not recommended as adjunctive therapy 3

Special Considerations

• Patients are generally non-contagious after 24 hours of appropriate antibiotic therapy 1
• Chronic carriers generally do not require treatment unless special circumstances exist (community outbreak of rheumatic fever, family history of rheumatic fever) 1, 3
• For chronic carriers requiring eradication, clindamycin 20-30 mg/kg/day divided into 3 doses (maximum 300 mg per dose) for 10 days is recommended 1
• Consider local macrolide resistance patterns before prescribing azithromycin or clarithromycin, as resistance varies geographically 1, 3