New Clinical Decision-Making Tool PEN-FAST Validated for Evaluation of Penicillin Allergy

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New data led to positive results for the simple-to-use PEN-FAST tool, allowing its use among allergists and even primary care physicians in cases in which access to allergists is limited.

The clinical decision-making tool known as PEN-FAST had a high negative predictive value of 100%, according to new findings, allowing for safe identification of those with low-risk penicillin allergy who may shift to oral penicillin without prior skin testing.1

These findings were the result of research conducted to further validate already existing clinical decision-making tools designed for penicillin allergy, given the need to enhance worldwide penicillin allergy delabeling.2

The research was authored by Jason H. Kwah, MD, MSc, from the Section of Rheumatology, Allergy and Immunology of the Department of Internal Medicine at Yale School of Medicine.

“We aimed to validate PEN-FAST in risk stratification of reported penicillin allergies at a large tertiary health care system outside of the country in which it was developed to further promote PEN-FAST use and enhance global penicillin allergy delabeling,” Kwah and colleagues wrote.

Background and Findings

The investigators performed a retrospective medical record review of nonpregnant patients with reported diagnoses of penicillin allergy who had undergone allergy testing at allergy and immunology outpatient clinics in the period between October of 2020, and July of 2022, in an American tertiary referral healthcare system.

The research team were given approval from the Yale University institutional review board, which waived the need for informed consent given that the data were de-identified. The cohort study adhered to the STROBE reporting guidelines.

The team’s allergy testing procedures included skin prick in addition to intradermal testing, followed by an oral challenge following skin tests or direct oral challenge without prior skin testing. Positive penicillin allergy test results were determined by positive skin test results or allergic reactions to oral challenges within 60 minutes.

The investigators compared the PEN-FAST tool’s scores with these outcomes. Additionally, specificity, sensitivity, negative predictive value (NPV), and positive likelihood ratio were calculated by the research team for each PEN-FAST score to predict allergy to penicillin.

The overall diagnostic performance of the tool was assessed by calculating the area under the receiver operating characteristic curve. In total, the investigators had 120 patients participate in their study, with a median age of 54 years.
Among these 120 study participants, 79.2% of them were reported to be female. Direct challenges were performed in 13.3% of the participants.

The research team’s analysis showed that the participants who underwent direct challenge— indicated by DC—had PEN-FAST scores of either 0 (in 4.2%) or 1 (in 9.2%). None of these participants reported experiencing immune- or non immune-mediated reactions.

With regard to PEN-FAST scores, 73.3% were noted as having scored 2 or less, which suggests a low risk. Furthermore, all of these individuals had negative test results. 3.4% of the participants obtained positive penicillin test results.

Specifically, 2 participants were found to have had positive skin test results and a PEN-FAST score of 3, while the other 2 individuals had negative skin test results but then failed oral challenges. Their PEN-FAST scores were reported to be 3 and 5, respectively.

Overall, the investigators reported that PEN-FAST scores of 2 or less were shown to be highly predictive of penicillin allergies, with a specificity, sensitivity, negative predictive value (NPV), and positive likelihood ratio of 75.9% (95% CI, 67.0% - 83.3%), 100% (95% CI, 39.8% - 100%), 100% (95% CI, 95.9% - 100%), and 4.14 (95% CI, 3.00 - 5.72), respectively.

Additionally, the research team noted that the area under the receiver operating characteristic curve was found to be 0.88 (95% CI, 0.84 - 0.92).

“The findings support those of a previous study1 and subsequent validation in a European single-center study, and advocate for the use of PEN-FAST as an accurate clinical decision-making tool to enhance penicillin allergy evaluations and promote greater use of direct penicillin challenge,” they wrote.


  1. Su C, Belmont A, Liao J, Kuster JK, Trubiano JA, Kwah JH. Evaluating the PEN-FAST Clinical Decision-making Tool to Enhance Penicillin Allergy Delabeling. JAMA Intern Med. Published online June 20, 2023. doi:10.1001/jamainternmed.2023.1572.
  2. Trubiano JA, Vogrin S, Chua KYL, et al. Development and validation of a penicillin allergy clinical decision rule. JAMA Intern Med. 2020;180(5):745-752. doi:10.1001/jamainternmed.2020.0403.