How Effective Is Penicillin Skin Testing?

Michael J. Postelnick, BSPharm
Senior Infectious Diseases Pharmacist, Clinical Coordinator, Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois

Determining whether a patient who reports being allergic to penicillin (PCN) can safely receive a PCN or other beta-lactam drug can be difficult. Dr. Lomaestro, in a previous article,[1] outlined the mechanisms associated with PCN reactions. Immediate reactions, which are immunoglobulin (Ig)E-mediated, are of the greatest concern, because they are more often life-threatening. Although careful history-taking will identify patients with clear recollection of serious reactions, vague or lack of recall of the type or severity of reaction does not rule out the possibility of anaphylaxis. PCN skin testing has the potential to identify patients at high risk for a severe reaction. Before using this method, however, it is important to be aware of associated caveats and limitations.

The immunogenic components of PCN, which result from the opening of the PCN ring under physiologic conditions, have been well-defined. The major determinant is benzylpenicilloyl, whereas minor determinants are penicillin G (benzylpenicillin), penicilloate, and penilloate.[2] The major determinant, conjugated to a polylysine carrier molecule, is again available as a commercial product (Pre-Pen®).[3] Minor determinants other than PCN G are not commercially available. Some allergists, primarily in major medical centers, synthesize minor determinates and do have them available for skin testing. AllerQuest, LLC plans to develop and test a minor determinant mixture.

In major medical centers, it may be possible to obtain an allergy service consultation to have skin testing undertaken with both major and minor determinants. The predictive value of a negative skin test has been reported to be 97% to 99%.[1] In areas without an allergy service resource, PCN skin testing may still be undertaken. Testing with benzylpenicilloyl polylysine (Pre-Pen®) alone reportedly identifies up to 90% of patients likely to have IgE-mediated reactions to PCN.[3] The addition of PCN G to the testing regimen raises the predictive value to 97%.[3]

Although these data are encouraging with respect to the ability of skin testing with major and minor determinants to identify patients at high risk, notes of caution have been raised[2,4,5]:

  • Large patient cohorts suggest that as many as 30% of patients with IgE-mediated allergy to PCN and other beta-lactams may be missed by routine skin testing;
  • Before the risk for an immediate reaction can be ruled out, and regardless of skin test results, patients should receive a graded challenge of the drug in question in settings with readily available emergency medical support; and
  • Testing should be delayed until the effect of interfering drugs, such as histamine-1 antagonists and vasopressors, has diminished.

Given the uncertainty, it is prudent to use the expertise of a trained allergist, if available, to assess patients who you suspect may have had serious reactions to beta-lactam agents. A positive skin test result should rule out the use of PCN agents and other beta-lactams, however a negative skin test does not definitively rule out the risk for an IgE-mediated reaction upon administration of the offending agent. Careful administration of the first dose of medication under controlled medical conditions is necessary to minimize the risk of untoward outcomes.