PENFAST-A: A Modified Clinical Decision Rule for ß-Lactam Allergy Risk Stratification in a Tertiary Allergy Center

Penicillin allergy labels are common and frequently inaccurate, leading to suboptimal antibiotic use. The PENFAST clinical decision rule has been validated to identify patients at low risk of true penicillin allergy; however, its performance may be limited in allergist-led settings, where specific low-risk clinical phenotypes are prevalent.

To develop and evaluate PENFAST-A, a modified version of the PENFAST score incorporating common allergy phenotypes observed in specialist practice, and to assess its diagnostic performance in a real-world cohort.

We conducted a retrospective study in a tertiary Allergy Unit including patients with a reported β-lactam allergy who underwent a standardized diagnostic workup. PENFAST and PENFAST-A scores were calculated retrospectively. Diagnostic performance metrics, including sensitivity, specificity, and predictive values, were compared between the two models.

In our cohort, PENFAST-A demonstrated higher sensitivity than the original PENFAST score (94.9% vs 81.8%), with a corresponding increase in negative predictive value (97.4% vs 93.5%). PENFAST-A reclassified a larger proportion of patients into higher-risk categories, resulting in lower specificity (44.2%). Importantly, no patients with a PENFAST-A score <2 had a confirmed β-lactam allergy, supporting its safety for identifying low-risk patients suitable for delabeling without further testing.

PENFAST-A improves the identification of low-risk patients with reported β-lactam allergy in allergist-led settings by incorporating clinically relevant phenotypes. This modified score may serve as a practical screening tool to guide safe delabeling and direct oral challenge in specialized clinical practice.