What is the next step for a patient with a sore throat and positive Group A Streptococcus (GAS) who has not responded to a course of amoxicillin and clindamycin?

Treatment of GAS Pharyngitis Not Responding to Amoxicillin and Clindamycin

Consider the patient a chronic GAS carrier experiencing a concurrent viral pharyngitis rather than treatment failure, and avoid further antibiotics unless specific high-risk circumstances exist. 1

Understanding the Clinical Scenario

When a patient with positive GAS pharyngitis fails to respond to both amoxicillin and clindamycin, you are most likely dealing with a chronic pharyngeal GAS carrier who has developed an intercurrent viral infection, not a true treatment failure. 1

Key Distinguishing Features

Chronic carriers exhibit:

• Positive throat cultures for GAS without evidence of active immunologic response (no rising anti-streptococcal antibody titers) 1
• Persistence of GAS colonization for ≥6 months 1
• Symptoms more consistent with viral pharyngitis (cough, rhinorrhea, hoarseness, conjunctivitis) rather than classic streptococcal features 1
• Up to 20% of asymptomatic school-age children may be GAS carriers during winter/spring 1

True treatment failures would show:

• Classic streptococcal symptoms (sudden onset, severe sore throat, fever, tonsillar exudates, anterior cervical adenopathy) 1
• Worsening or persistent symptoms despite adequate antibiotic therapy 1
• Documented compliance with prescribed antibiotics 1

Recommended Management Approach

For Most Patients (Chronic Carriers)

Do NOT prescribe additional antibiotics. 1 Chronic GAS carriers:

• Are unlikely to spread GAS to close contacts 1
• Have very low or no risk of developing suppurative complications or acute rheumatic fever 1
• Do not benefit from repeated antimicrobial courses 1

Provide symptomatic treatment only:

• Analgesics (acetaminophen or NSAIDs) for pain and fever 1
• Warm salt water gargles 1
• Topical anesthetics if age-appropriate 1

Special Circumstances Requiring Carrier Eradication

Consider aggressive carrier eradication therapy ONLY in these specific situations: 1

1. Community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis, or invasive GAS infection 1
2. Outbreak of GAS pharyngitis in a closed/partially closed community 1
3. Personal or family history of acute rheumatic fever 1
4. Family with excessive anxiety about GAS infections 1
5. Tonsillectomy being considered solely because of carrier state 1

Carrier Eradication Regimens (When Indicated)

If carrier eradication is necessary, use one of these evidence-based regimens: 1

First-line option (Strong, High quality evidence):

• Clindamycin 20-30 mg/kg/day in 3 divided doses (maximum 300 mg/dose) for 10 days 1
• This is the most effective single-agent oral regimen, achieving 85-92% eradication rates 2

Alternative regimens (Strong, High quality evidence):

• Penicillin V 50 mg/kg/day in 4 doses for 10 days (maximum 2000 mg/day) PLUS rifampin 20 mg/kg/day in 1 dose for the last 4 days (maximum 600 mg/day) 1
• Intramuscular benzathine penicillin G (600,000 U if <27 kg; 1,200,000 U if ≥27 kg) as single dose PLUS oral rifampin 20 mg/kg/day in 2 doses for 4 days (maximum 600 mg/day) 1

Alternative oral option (Strong, Moderate quality evidence):

• Amoxicillin-clavulanate 40 mg amoxicillin/kg/day in 3 doses for 10 days (maximum 2000 mg amoxicillin/day) 1

Critical Pitfalls to Avoid

Do not routinely perform post-treatment cultures in asymptomatic patients, as this leads to unnecessary identification of carriers and inappropriate antibiotic prescribing. 1 Post-treatment testing is indicated only for:

• Patients who remain symptomatic 1
• Patients whose symptoms recur 1
• Patients with personal history of rheumatic fever 1

Do not screen or treat household contacts unless they are symptomatic or in the special circumstances listed above. 1

Recognize that repeated antibiotic courses in asymptomatic carriers are rarely indicated and may promote antibiotic resistance without clinical benefit. 1

Consider compliance issues before assuming true treatment failure—if adherence to oral therapy is questionable and true infection is suspected, intramuscular benzathine penicillin G should be considered. 1

When True Treatment Failure is Suspected

If you genuinely believe this represents true treatment failure (persistent classic streptococcal symptoms, documented compliance, no viral features), consider:

• Intramuscular benzathine penicillin G (600,000 U if <27 kg; 1,200,000 U if ≥27 kg) as single dose, which has higher eradication rates than oral therapy 1
• First-generation cephalosporin (e.g., cephalexin 20 mg/kg/dose twice daily for 10 days, maximum 500 mg/dose) 1
• Amoxicillin-clavulanate as noted above 1

However, this scenario is uncommon given that the patient has already failed both amoxicillin and clindamycin—two agents with different mechanisms that should cover GAS effectively. 1