Treatment of Rheumatic Fever
Penicillin remains the definitive treatment for acute rheumatic fever and prevention of recurrence, with intramuscular benzathine penicillin G being the gold standard for secondary prophylaxis due to superior efficacy compared to oral regimens. 1
Acute Treatment Phase
Initial Antibiotic Therapy to Eradicate Streptococcus
Administer a full therapeutic course of penicillin immediately upon diagnosis of acute rheumatic fever, even if throat culture is negative, to eradicate any residual group A Streptococcus. 2, 3
Penicillin V oral: 250 mg twice daily for children or 500 mg 2-3 times daily for adolescents/adults for 10 days. 1
Amoxicillin oral: 50 mg/kg once daily (maximum 1000 mg) for 10 days is an acceptable alternative, particularly for young children due to better palatability of the suspension. 1
Benzathine penicillin G intramuscular: Single injection of 1.2 million units is preferred for patients unlikely to complete oral therapy or those with high-risk factors (crowded living conditions, low socioeconomic status, personal/family history of rheumatic fever). 1
For penicillin-allergic patients: Erythromycin or other macrolides for 10 days, though <5% of group A Streptococcus isolates in the United States show erythromycin resistance. 1, 4
Critical Timing Considerations
Therapy can be safely postponed up to 9 days after symptom onset and still prevent rheumatic fever, allowing time for throat culture confirmation without increasing risk. 1
Patients become non-contagious after 24 hours of antibiotic therapy. 1
Secondary Prophylaxis (Prevention of Recurrence)
First-Line Regimen
Benzathine penicillin G 1.2 million units intramuscularly every 4 weeks is the standard regimen with the strongest evidence (Class I, LOE A) for preventing recurrent rheumatic fever. 2, 3
This regimen is approximately 10 times more effective than oral antibiotics (0.1% vs 1% recurrence rate). 2, 5, 6
For high-risk populations or patients with recurrence despite adherence to the 4-week regimen, administer benzathine penicillin G every 3 weeks. 2, 7, 8
The 3-week regimen reduces streptococcal infections (7.5 vs 12.6 per 100 patient-years) and prophylaxis failure (0.25 vs 1.29 per 100 patient-years) compared to the 4-week regimen. 8
Serum penicillin levels remain adequate (≥0.02 mcg/mL) in 56% of patients at 21 days versus only 33% at 28 days, explaining the superiority of the 3-week interval. 8
Alternative Oral Regimens (For Penicillin-Allergic Patients)
Penicillin V oral: 250 mg twice daily for children or 500 mg 2-3 times daily for adolescents/adults. 2, 3
Sulfadiazine oral: 1 gram once daily for adults or 0.5 gram once daily for patients weighing ≤27 kg. 2, 3
Erythromycin: Recommended by the American Heart Association for penicillin and sulfonamide-allergic patients for long-term prophylaxis. 4
Duration of Secondary Prophylaxis Based on Cardiac Involvement
The duration must be individualized based on presence and severity of carditis:
Rheumatic fever WITH carditis AND persistent valvular disease: Continue prophylaxis for 10 years after last attack OR until age 40, whichever is longer. 2, 3
Rheumatic fever WITH carditis but NO residual heart disease: Continue prophylaxis for 10 years after last attack OR until age 21, whichever is longer. 2, 3
Rheumatic fever WITHOUT carditis: Continue prophylaxis for 5 years after last attack OR until age 21, whichever is longer. 2, 3
Lifelong prophylaxis should be considered in high-risk patients based on severity of valvular disease and ongoing exposure to group A Streptococcus (teachers, healthcare workers, military recruits, parents of young children). 2, 3
Critical Clinical Considerations
Adherence and Efficacy
Intramuscular benzathine penicillin G is substantially superior to oral antibiotics because adherence is guaranteed with witnessed administration, whereas oral regimens depend on patient compliance. 5, 6
Good adherence to prophylaxis reduces odds of rheumatic fever recurrence or rheumatic heart disease progression by 71% compared to poor adherence. 7
To reduce injection pain, warm benzathine penicillin G to room temperature before administration. 1
Safety Profile
Life-threatening allergic reactions to benzathine penicillin G are extremely rare (less than 1-3 per 1000 individuals). 7
Hypersensitivity reactions and local injection site reactions are more common with intramuscular penicillin compared to no antibiotics, but serious adverse events (anaphylaxis, sciatic nerve injury) are rare. 6
Post-Valve Surgery Considerations
Secondary antibiotic prophylaxis must continue after valve surgery in adults with rheumatic heart disease, following the same duration guidelines as non-surgical patients. 3
This is a critical point: valve replacement does not eliminate the risk of recurrent acute rheumatic fever, as patients remain susceptible to group A Streptococcus infection. 3
Endocarditis Prophylaxis
Routine endocarditis prophylaxis is no longer recommended for patients with rheumatic heart disease unless they have prosthetic valves or prosthetic material used in valve repair. 2, 3
For patients receiving penicillin prophylaxis who require endocarditis prophylaxis for dental procedures, use an agent other than penicillin due to likely resistance of oral α-hemolytic streptococci. 2, 3
Common Pitfalls to Avoid
Never discontinue secondary prophylaxis after valve surgery—this is a dangerous misconception that increases recurrence risk. 3
Do not assume that a negative throat culture at diagnosis eliminates the need for initial antibiotic therapy—treat all acute rheumatic fever cases to eradicate potential residual Streptococcus. 2
Remember that at least one-third of rheumatic fever cases arise from asymptomatic group A Streptococcus infections, making primary prevention challenging and emphasizing the critical importance of secondary prophylaxis. 2
Even with optimal treatment of streptococcal pharyngitis, rheumatic fever can still occur in susceptible individuals, underscoring that secondary prophylaxis is the most effective protection against recurrence. 2