Lymphocyte transformation tests offer improved sensitivity over skin tests for lymphocytic sensitization in CF patients with allergy to antibiotics

Introduction Hypersensitivity to antibiotics remains a clinical challenge in the management of CF. Past reactions lead to the abstention of the antibiotics resulting in inconsistent treatments. The underlying immunomechanisms often remain unclear. This prospective trial performs regular intravenous treatment courses for a clinical indication with antibiotics, which were formerly labeled as allergic preceded by skin testing and lymphocyte transformation tests (LTT) to assess the diagnostic value of allergy testing.

Methods Participants were recruited at Charité Universitätsmedizin Berlin, Germany. Inclusion criteria were CF, age >12a and ≥1 intravenous antibiotic in abstention due to an allergic reaction. Skin prick and intracutaneous tests and the aquisition of a blood sample for the LTT were done before the provocation. LTT were performed in the Department of Molecular Pharmacology at the University of Liverpool, UK. The provocations were performed independently from the results of the skin tests and the LTT.

Results Out of 34 drug challenges, 13 (38%) led to a reaction. 9/13 (69%) reactions led to a discontinuation of treatment. All reactions were moderate. The majority of the reactions were cutaneous 65.4%. Piperacillin/Tazobactam accounted for eight of the positive challenges, Ceftazidime for three and Meropenem for one. The sensitivity of the LTT for prediction of a reaction was 38,5%, the specificity 100%, the positive predictive value 1 and the negative predictive value 0.68.

Discussion Our study demonstrates the ability of LTT to detect lymphocytic sensitization to Piperacillin/Tazobactam and Meropenem and to predict reactions. This suggests implementing LTT in the diagnostic workup of suspected drug allergy against these antibiotics. The data generated suggests avoidance of drug challenge in cases with a positive LTT to the culprit antibiotic. Furthermore, the study has shown that is safe to re-introduce allergic antibiotics and that there is a chance of 61% that the patient will not to react again.

Publication History

Article published online:
21 September 2022