What is the role of skin testing for benzathine penicillin (Bicillin) in prophylaxis for rheumatic fever?

From the Guidelines

Skin testing is not routinely recommended before administering benzathine penicillin G for rheumatic fever prophylaxis. Benzathine penicillin G is the preferred medication for secondary prevention of rheumatic fever, typically administered as 1.2 million units intramuscularly every 4 weeks (or every 3 weeks in high-risk patients) 1. For patients weighing less than 27 kg, the dose is 600,000 units. While penicillin allergy is a concern, the risk of serious allergic reactions to benzathine penicillin is low, and skin testing has poor predictive value for these reactions 1. Most reported penicillin allergies are not true allergies, and skin testing may create unnecessary barriers to this essential preventive therapy. Instead, a careful clinical history to assess for true penicillin allergy is more practical. For patients with confirmed severe penicillin allergy, alternative prophylaxis options include oral erythromycin (250 mg twice daily) or azithromycin, though these are less effective than benzathine penicillin 1. The primary goal of prophylaxis is preventing group A streptococcal infections that could trigger recurrent rheumatic fever and worsen rheumatic heart disease, making adherence to the prophylaxis regimen critical regardless of the medication used.

Some key points to consider:

• The prevalence of confirmed penicillin allergy is low, with less than 5% of individuals labeled with a penicillin allergy being confirmed to have a currently active acute onset IgE-mediated penicillin allergy or a clinically significant delayed onset T-cell-mediated penicillin hypersensitivity 1.
• Anaphylaxis and death following penicillin administration is rare, and the mechanism for anaphylaxis is IgE-mediated 1.
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions, but routine penicillin allergy testing in individuals without reported allergy and requiring therapy with a penicillin is not usually recommended due to the very low rate of anaphylaxis 1.
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide, and delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, or directly by clinical history taking alone 1.

From the FDA Drug Label

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bicillin L-A and other antibacterial drugs, Bicillin L-A should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria Medical Conditions in which Penicillin G Benzathine Therapy is indicated as Prophylaxis: Rheumatic fever and/or chorea—Prophylaxis with penicillin G benzathine has proven effective in preventing recurrence of these conditions.

The role of skin testing for benzathine penicillin (Bicillin) in prophylaxis for rheumatic fever is not mentioned in the provided drug labels.

• The labels discuss the use of benzathine penicillin for prophylaxis of rheumatic fever, but do not address skin testing.
• No conclusion can be drawn about the role of skin testing in this context. 2 2

From the Research

Role of Skin Testing for Benzathine Penicillin

• Skin testing for benzathine penicillin is crucial in determining whether a patient is allergic to penicillin, which is essential for secondary prophylaxis of rheumatic fever 3.
• Penicillin allergy skin testing is a simple and effective way to identify true penicillin allergy, and it should be conducted in a facility with available life-support equipment 3.
• The test involves testing for both major and minor determinants, and alternatives to skin testing include laboratory synthesis of major determinants, use of the radioallergosorbent test (RAST), or a combination of RAST and minor determinant skin testing 3.

Importance of Benzathine Penicillin in Rheumatic Fever Prophylaxis

• Benzathine penicillin G is the gold standard for secondary prophylaxis of rheumatic fever, and it is usually administered as a dose of 1,200,000 U (900 mg) every 3-4 weeks 4, 5, 6, 7.
• Studies have shown that injections every 3 weeks are superior to injections every 4 weeks in preventing recurrences of rheumatic fever 5, 6.
• The development of chronic valvular lesions after an episode of rheumatic fever is dependent on the presence or absence of carditis in the previous attack and compliance with secondary prophylaxis, and recurrences due to inadequate penicillin prophylaxis are responsible for hemodynamically significant chronic valvular lesions requiring surgery 7.

Administration and Compliance

• Compliance with benzathine penicillin G regimens is crucial for effective secondary prophylaxis of rheumatic fever, and patients should be monitored regularly to ensure adherence to the treatment regimen 4, 5, 6.
• The administration of benzathine penicillin G should be done in a facility with available life-support equipment, and patients with suspected penicillin allergy can undergo desensitization if they require penicillin therapy 3.