A point-of-care clinical decision rule may help identify patients who may be low risk despite reporting an allergy, as well as candidates for allergy delabeling and safe beta-lactam prescribing.
Researchers used clinical variables predictive of a positive penicillin allergy test result to develop the PEN-FAST rule, which they derived and internally validated in a multicenter prospective antibiotic allergy-tested cohort of 622 patients (median age, 60 years; 59% women) from two tertiary care sites in Melbourne, Australia. They then externally validated the model retrospectively in three geographically dispersed penicillin allergy-tested cohorts consisting of 945 patients (median age, 55 years; 70% women) from Sydney and Perth, Australia, and Nashville, Tenn. Patients had penicillin allergy testing using skin prick, intradermal, or patch testing and/or oral challenge (direct or after skin testing). The primary outcome for the model was any positive result of penicillin allergy testing performed during outpatient or inpatient assessment. Data were collected from June 26, 2008, to June 3, 2019, and results were published online on March 16 by JAMA Internal Medicine.
Among the three cohorts, the features associated with a positive penicillin allergy test result on multivariable analysis were summarized in the mnemonic PEN-FAST: PENicillin allergy, Five or fewer years ago, Anaphylaxis/angioedema, Severe cutaneous adverse reaction, and Treatment required for allergy episode. Major criteria were an allergy event occurring within the past five years (2 points) and anaphylaxis/angioedema or severe cutaneous adverse reaction (2 points), and the minor criterion was treatment required for an allergy episode (1 point). Risk was categorized into four groups: very low (0 points), with a risk of allergy of 0.6%; low (1 or 2 points), with a risk of 5%; moderate (3 points), with a risk of 20%; and high (4 or 5 points), with 50% probability of having a positive penicillin test result. The researchers chose a cutoff of less than 3 points for PEN-FAST to classify a low risk of penicillin allergy. Only 17 of 460 patients (3.7%) had positive results of allergy testing, with a negative predictive value of 96.3% (95% CI, 94.1% to 97.8%). Findings remained clinically relevant in the external validation.
The study authors noted limitations to the PEN-FAST rule, such as the exclusion of nonpenicillin beta-lactam allergies and some IV penicillins and the predominance of inpatient testing. They added that an important next step for future research is to validate the decision rule in ethnically diverse populations (e.g., European, Asian, and African), where the prevalence of penicillin allergy and phenotypes is likely to vary.
“Due to the inherent error rate in the electronic health record, we would advise that PEN-FAST be applied only on a detailed clinical history obtained directly from the patient rather than electronic health record data only,” the authors recommended.