Allergy testing to confirm penicillin hypersensitivity in adults

Ideally, all patients who report penicillin hypersensitivity should have allergy testing to verify their allergy. Take an extensive allergy history first to ascertain if it is appropriate to directly delabel a patient’s allergy. The PEN-FAST Penicillin Allergy Decision Rule and the Beta-lactam antibiotic allergy assessment tool can be used to assess the patient’s penicillin allergy risk.

Skin testing, including skin-prick and intradermal testing, is the standard method used to test for immediate (IgE-mediated) penicillin hypersensitivity; it should be performed by specialist clinicians. In patients with severe penicillin hypersensitivity, skin testing is typically used before oral challenge.

Oral challenge (also called drug challenge, drug provocation testing, graded challenge or test dosing) is the controlled administration of a drug to diagnose hypersensitivity. Oral challenge remains the gold standard for penicillin allergy testing; it should only be performed under medical supervision, after consultation with a specialist. Direct oral challenge (ie oral challenge without prior skin testing) has been performed safely in a large cohort of Australian inpatients reporting a low-risk penicillin allergyChua 2021Trubiano 2022; 96% of patients who had direct oral challenge did not have a reaction on single-dose provocationChua 2021Rose 2020Trubiano 2022. Patients who may be appropriate for direct oral challenge include those with:

• a low-risk nonsevere penicillin allergy based on formal risk assessment
• a reported low-risk penicillin allergy (eg a history of benign or unspecified rash in childhood, maculopapular exanthem more than 5 to 10 years ago)
• an unknown reaction that occurred more than 5 to 10 years ago
• a predictable adverse drug reaction (eg gastrointestinal intolerance, localised injection site reaction alone) where direct delabeling was not accepted by the patient.

In patients with delayed nonsevere penicillin hypersensitivity, prolonged oral challenge (over 3 to 7 days) following a supervised single-dose direct oral challenge has been used, but this is not routinely recommended.

Do not perform direct oral challenge without prior skin testing in patients with a history of severe (immediate or delayed) penicillin allergy.

For more information, see Allergy testing to confirm antimicrobial hypersensitivity.

A practical approach to inpatient penicillin allergy assessment and delabeling programmes can be found in this position paper produced by the National Antibiotic Allergy NetworkHannah 2024.