Can rheumatic fever develop after antibiotic therapy for acute infections?

From the Guidelines

Rheumatic fever can still develop after antibiotic therapy for acute infections, although the risk is significantly reduced with timely and appropriate treatment. The development of rheumatic fever is an autoimmune response to the strep bacteria, and in some cases, this response may have already been triggered before antibiotics could eliminate the infection 1. According to the American Heart Association, primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A -hemolytic streptococcal (GAS) tonsillopharyngitis 1.

The recommended treatment for GAS pharyngitis is penicillin, either oral penicillin V or injectable benzathine penicillin, due to its cost-effectiveness, narrow spectrum of activity, and proven efficacy 1. For penicillin-allergic individuals, acceptable alternatives include a narrow-spectrum oral cephalosporin, oral clindamycin, or various oral macrolides or azalides 1.

Even with proper antibiotic treatment, there's a small risk that rheumatic fever could still develop, and patients should be monitored for symptoms of rheumatic fever, such as joint pain, fever, and skin rashes, even after completing antibiotic therapy for strep throat 1. The risk of treatment failure is higher with oral penicillin than with intramuscular benzathine penicillin G, and repeated courses of antibiotic therapy are rarely indicated in asymptomatic patients who continue to harbor GAS after appropriate therapy 1.

Key points to consider in the management and prevention of rheumatic fever include:

• Timely and appropriate antibiotic treatment for GAS pharyngitis
• Monitoring for symptoms of rheumatic fever after antibiotic therapy
• Consideration of alternative treatments for penicillin-allergic individuals
• Awareness of the risk of treatment failure and the potential need for repeated courses of antibiotic therapy 1.

From the FDA Drug Label

NOTE: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the prophylaxis of rheumatic fever. Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.

Rheumatic Fever Development: The FDA drug label does not provide direct information on whether rheumatic fever can develop after antibiotic therapy for acute infections. However, it mentions that penicillin is the usual drug of choice for prophylaxis of rheumatic fever, implying that rheumatic fever can still occur if prophylaxis is not effective or if the infection is not fully treated.

• Key Point: The labels do not provide direct evidence to answer the question, but they suggest that rheumatic fever can be prevented with appropriate antibiotic therapy, such as penicillin.
• Clinical Decision: It is unclear if rheumatic fever can develop after antibiotic therapy, and the labels do not provide enough information to make a conclusion. 2

From the Research

Rheumatic Fever Development After Antibiotic Therapy

• Rheumatic fever can develop after antibiotic therapy for acute infections, as the primary prevention of rheumatic fever depends on approved antibiotic treatment of streptococcal pharyngitis 3, 4, 5, 6.
• The risk of developing rheumatic fever after antibiotic therapy is reduced, but not eliminated, as evidenced by a meta-analysis showing a 70% protective effect for the use of antibiotics against acute rheumatic fever 6.
• The development of rheumatic fever after antibiotic therapy may be influenced by various factors, including the type and duration of antibiotic treatment, the severity of the initial infection, and individual patient characteristics 7, 4, 5.

Antibiotic Prophylaxis and Rheumatic Fever Recurrence

• Antibiotic prophylaxis, particularly with intramuscular benzathine benzylpenicillin, has been shown to reduce the risk of recurrence of rheumatic fever compared to no antibiotics or oral antibiotics 7, 4.
• The effectiveness of antibiotic prophylaxis in preventing rheumatic fever recurrence may depend on factors such as the duration of treatment, the frequency of injections, and patient adherence to the treatment regimen 7, 4.
• Secondary prophylaxis with benzathine penicillin G has been shown to decrease the incidence of rheumatic heart disease (RHD) and is key to RHD control 4.

Limitations and Future Research Directions

• The majority of studies on antibiotic prophylaxis and rheumatic fever recurrence were conducted over 50 years ago, and the methodology was often at high risk of bias 7.
• There is a need for ongoing research to understand who benefits most from prophylaxis, to find novel therapies to reduce the incidence of rheumatic fever, and to reduce the prevalence of RHD 7, 4.
• RHD research is neglected and underfunded, highlighting the need for RHD advocacy and public health awareness to increase research on RHD 4.