What is the first‑line antibiotic for a Group A Streptococcus infection in a patient with a heart murmur?

Best Antibiotic for Group A Streptococcus in a Patient with a Heart Murmur

For a patient with Group A Streptococcus pharyngitis and a heart murmur, prescribe penicillin or amoxicillin as first-line therapy—the same regimen used for patients without murmurs—because Group A Streptococcus remains uniformly susceptible to beta-lactams worldwide, and the presence of a murmur does not change the antibiotic choice for uncomplicated pharyngitis. 1

Treatment Algorithm Based on Penicillin Allergy Status

Non-Allergic Patients (First-Line)

• Amoxicillin 500 mg orally twice daily for 10 days is the preferred regimen for adults with confirmed Group A Streptococcus pharyngitis, regardless of murmur presence. 1
• For children, prescribe amoxicillin 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days. 1
• Penicillin V 500 mg orally twice daily for 10 days is equally effective but less palatable in children. 1

Non-Immediate (Delayed) Penicillin Allergy

• First-generation cephalosporins are the preferred alternative, with only 0.1% cross-reactivity risk in patients with non-severe, delayed penicillin reactions. 1
• Prescribe cephalexin 500 mg orally twice daily for 10 days in adults, or 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days in children. 1
• Cefadroxil 1 gram once daily for 10 days is an acceptable once-daily alternative. 1

Immediate/Anaphylactic Penicillin Allergy

• Clindamycin 300 mg orally three times daily for 10 days is the preferred choice for adults with immediate hypersensitivity reactions, with only ~1% resistance among Group A Streptococcus in the United States. 1, 2
• For children, prescribe clindamycin 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days. 1
• Azithromycin 500 mg once daily for 5 days (adults) or 12 mg/kg once daily for 5 days (children, maximum 500 mg) is acceptable but has 5–8% macrolide resistance rates. 1

Critical Treatment Duration Requirement

• A full 10-day course is mandatory for all antibiotics except azithromycin to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever, even if symptoms resolve within 3–4 days. 1
• Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 1
• Azithromycin requires only 5 days due to its prolonged tissue half-life and unique pharmacokinetics. 1

Why the Murmur Does Not Change Antibiotic Selection

• Group A Streptococcus pharyngitis is treated identically whether or not a murmur is present, because the goal is preventing acute rheumatic fever and suppurative complications through adequate pharyngeal eradication. 1
• The European Society of Cardiology guidelines address Group A Streptococcus endocarditis separately—if the patient has confirmed infective endocarditis (not just a murmur), then intravenous penicillin G 12–18 million units/day for 4 weeks is required, with treatment similar to other penicillin-susceptible streptococci. 3
• For invasive Group A Streptococcus infections including bacteremia or endocarditis, high-dose intravenous penicillin G (12–24 million units/day) PLUS clindamycin (600–900 mg IV every 8 hours) is recommended, as clindamycin suppresses toxin production and improves survival. 4

Common Pitfalls to Avoid

• Do not use trimethoprim-sulfamethoxazole (Bactrim) for Group A Streptococcus pharyngitis—sulfonamides fail to eradicate the organism in 20–25% of cases. 1
• Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to up to 10% cross-reactivity risk with all beta-lactams. 1
• Do not assume the murmur indicates endocarditis without clinical evidence—most murmurs in pharyngitis patients are functional or pre-existing valvular abnormalities unrelated to the current infection. 3
• Do not shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen) despite clinical improvement, as this dramatically increases treatment failure and rheumatic fever risk. 1

When to Suspect Endocarditis Rather Than Simple Pharyngitis

• If the patient has persistent fever despite 48–72 hours of appropriate antibiotics, new or changing murmur, positive blood cultures, or signs of systemic embolization, obtain an echocardiogram and consider infective endocarditis. 3
• Group A Streptococcus endocarditis is rare but can occur even in structurally normal hearts, requiring 4 weeks of intravenous penicillin G rather than oral therapy. 3, 5