Cephalosporin Allergy Tools Show High Negative Predictive Value

CEPH-FAST and the Vanderbilt criteria showed high negative predictive values (NPVs) in an external validation study of adults evaluated for cephalosporin allergy, but sensitivity fell when intravenous allergy labels were excluded. The cross-sectional study, published in JAMA Network Open, also found that documentation was insufficient to score the Urticaria 1-1-1 tool for most patients.

Investigators retrospectively reviewed records from 121 adults with cephalosporin allergy labels who completed evaluation at a Yale University–affiliated clinic. Evaluation included skin testing followed by drug challenge when testing was negative, or a direct cephalosporin challenge. A positive skin test or an allergist-adjudicated immune-mediated reaction was considered a verified allergy.

Overall, 23 patients (19.0%) had a verified cephalosporin allergy. CEPH-FAST could be scored from clinical documentation for 120 patients (99.2%), and the Vanderbilt criteria for 106 patients (87.6%); Urticaria 1-1-1 could be scored for only 9 patients (7.4%). CEPH-FAST had a specificity of 84.5% and an NPV of 94.3%, while the Vanderbilt criteria had a specificity of 88.2% and an NPV of 96.2%. Areas under the receiver operating characteristic curve were 0.81 and 0.87, respectively.

In analyses excluding intravenous cephalosporin allergy labels, sensitivity decreased from 78.3% to 33.3% for CEPH-FAST and from 85.7% to 25.0% for the Vanderbilt criteria. The investigators said the tools were better at identifying patients with low-risk histories for direct challenge than identifying cases of true allergy and emphasized considering the route of the implicated cephalosporin alongside a comprehensive allergy history.

Limitations included the retrospective, single-center design and a predominantly female, White population with atopic comorbidities. The sample was enriched for true allergy, and positive skin test results may have included false positives because the diagnostic validity of cephalosporin skin testing is not well established. The authors called for validation in other populations and specifically among patients with intravenous cephalosporin allergy labels.

Source: Belmont AP, Valente M, Workineh A, et al. Performance of risk stratification tools for cephalosporin allergy testing. JAMA Netw Open. 2026;9(9):e2634079. doi:10.1001/jamanetworkopen.2026.34079