Development and validation of a cephalosporin allergy clinical decision rule

Authors:

• Cox, F.
• Vogrin, S.
• Sullivan, R.P.
• Stone, C.
• Koo, G.
• Phillips, E.
• Li, J.
• Fernando, S.L.
• Al Gassim, M.
• Mitri, E.
• De Luca, J.
• Rose, M.
• Chua, K.Y.L.
• Holmes, N.E.
• Copaescu, A.M.
• Trubiano, J.A.

Details:

Journal of Infection, Volume 90, Issue 6, 2025-06-30

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Background Like penicillin allergy labels, cephalosporin allergy labels go largely unverified and drive inappropriate antibiotic use. Clinical decision rules (CDR) have been validated to identify low-risk penicillin allergy labelled patients suitable for direct oral challenge (DOC); however, the generalisability to cephalosporin allergy remains uncertain. Methods Cephalosporin allergy tested cohorts from three hospitals in Australia were used for validation of a cephalosporin allergy CDR based on clinical variables utilised in the published penicillin allergy decision rule (PEN-FAST). Patients with a cephalosporin allergy label underwent allergy testing. North American tested cohorts were used for external validation. Findings From an Australian validation cohort of 228 patients and an external cohort of 167 patients, the four clinical features associated with a positive penicillin allergy from PEN-FAST showed similar associations to a positive cephalosporin test, with minor adjustments to scoring. Validation showed an AUROC of 0.921. A cut-off of less than three points for the newly directed CEPH-FAST was chosen to classify a low risk of cephalosporin allergy, for which six of 105 patients (5.7%) had positive allergy testing results. Interpretation Utilising the previously published and internationally validated tool PEN-FAST, we validated the same criteria with minor modifications for low-risk cephalosporin allergies. The results suggest that a CEPH-FAST score of less than three is associated with a high negative predictive value and could be used by clinicians and antimicrobial stewardship programmes to identify patients with low-risk cephalosporin allergies at the point of care, following local validation, who could proceed to DOC or use non-cross-reactive cephalosporins.