What is the skin test for benzathine (Bicillin) penicillin?

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Last updated: March 26, 2025View editorial policy

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From the Guidelines

Skin testing for benzathine penicillin is not recommended as a routine practice before administration, and benzathine penicillin G should be administered without prior skin testing unless the patient has a documented history of penicillin allergy. If a patient reports a penicillin allergy, proper evaluation by an allergist is preferred over skin testing at the point of care. The traditional penicillin skin test uses benzylpenicilloyl-polylysine (Pre-Pen) and penicillin G, not benzathine penicillin itself, as benzathine penicillin is a repository form designed for slow release and is not suitable for skin testing 1. For patients with suspected penicillin allergy who require treatment, referral to an allergist for comprehensive evaluation is the best approach. This evaluation may include skin testing with appropriate reagents followed by oral challenge if skin tests are negative. The rationale behind avoiding routine skin testing is that false positives can occur, leading to unnecessary avoidance of an effective antibiotic, while false negatives don't completely eliminate the risk of a reaction. Additionally, most patients who report penicillin allergy are not truly allergic when properly evaluated 1.

Some key points to consider:

  • The negative predictive value of penicillin skin testing is between 97% and 99%, depending on the skin test reagents used 1.
  • Patients with negative penicillin skin test responses might be safely treated with penicillin, and depending on the reagents used for skin testing, the therapeutic dose might be preceded by a test dose 1.
  • Penicillin skin testing is safe in that the risk of inducing serious reactions during properly performed penicillin skin testing is comparable with the risk of other types of skin testing 1.
  • Skin testing with semisynthetic penicillins, such as ampicillin or amoxicillin, is not standardized, and its predictive value is unknown 1.
  • Penicillin skin testing should not be performed on patients with histories of severe non–IgE-mediated allergic reactions to penicillin, such as Stevens-Johnson syndrome or toxic epidermal necrolysis 1.

In terms of the specific skin test for benzathine penicillin, the traditional penicillin skin test uses benzylpenicilloyl-polylysine (Pre-Pen) and penicillin G, not benzathine penicillin itself. The use of benzathine penicillin for skin testing is not recommended due to its slow release formulation, which makes it unsuitable for this purpose 1. Instead, benzylpenicilloyl-polylysine (Pre-Pen) and penicillin G are used as they are more suitable for skin testing and can help identify patients who are allergic to penicillin 1.

From the Research

Skin Test for Benzathine (Bicillin) Penicillin

  • The skin test for benzathine (Bicillin) penicillin is not directly mentioned in the provided studies, but the skin test for penicillin allergy is discussed in several studies 2, 3, 4, 5, 6.
  • Penicillin skin testing is an accurate method to determine whether a person with a history of penicillin allergy is at risk of having an immediate reaction to penicillin 2.
  • The skin test for penicillin allergy typically involves the use of penicilloyl-polylysine (PPL) and/or minor determinant mixture (MDM) 3, 4, 5.
  • The use of benzylpenicillin alone as a minor determinant may not be sufficient to detect all patients at risk of an immediate hypersensitivity reaction 5.
  • Skin testing with PPL and MDM has been shown to be safe and effective in identifying patients at risk of allergic reactions to penicillin 3, 4, 5.
  • The negative predictive value of penicillin skin testing is high, ranging from 97% to 99% 4, 5.

Procedure and Interpretation

  • The skin test procedure typically involves puncture and intradermal testing with PPL and/or MDM 3, 6.
  • A negative skin test reaction suggests that the patient is not at risk of an immediate hypersensitivity reaction to penicillin 2, 3, 4, 5.
  • A positive skin test reaction indicates that the patient is at risk of an allergic reaction to penicillin 3, 4, 5.

Clinical Implications

  • Penicillin skin testing can be used to safely identify patients who can receive beta-lactam antibiotics without concern for serious acute allergy 5.
  • The results of penicillin skin testing can be used to modify antibiotic coverage and reduce the use of broad-spectrum antibiotics 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Skin testing to detect penicillin allergy.

The Journal of allergy and clinical immunology, 1981

Research

Penicillin allergy: a practical approach to management.

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 1986

Research

Penicillin minor determinants: History and relevance for current diagnosis.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2018

Research

Evaluating Penicillin Allergies Without Skin Testing.

Current allergy and asthma reports, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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