Abstract
Piperacillin-tazobactam is used in patients with cystic fibrosis to treat recurrent respiratory infections. Exposure is associated with a high frequency of non-immediate hypersensitivity.
To assess the applicability of the lymphocyte transformation test (LTT) for the diagnosis of piperacillin hypersensitivity and the influence of desensitization on piperacillin-specific T-cell responses.
Study-arm one was an analysis of LTT responses from 58 naïve/baseline tolerant patients with samples collected over a three-year interventional phase. In study-arm two, seventeen hypersensitive patients were recruited and LTTs were conducted before and post-desensitization. Clinical hypersensitivity reactions in both arms were monitored over an eight-year observational period.
Fifty-eight patients in study arm one received 611 (range, 2-40; mean±SD, 10.5±8.1) piperacillin-tazobactam courses during the interventional phase, of which 11 developed hypersensitivity. The patients that remained tolerant received 236 piperacillin-tazobactam courses in the observational period, of which 9 developed hypersensitivity. Ten/eleven interventional phase hypersensitive patients had a positive LTT, while one remained negative. 136 negative LTTs were recorded with 39 tolerant patients, while eight patients recorded a positive LTT, with 4 developing hypersensitivity during the observational period. Ten LTT positive patients in study arm two underwent piperacillin-tazobactam desensitization, with seven tolerating the drug. The strength of the LTT decreased during desensitization and negative results were recorded for a minimum of 14-days. During follow-up, eight patients tolerated 62 piperacillin-tazobactam courses through desensitization.
LTT is a sensitive marker of drug sensitisation that could be used to inform future patient management. Desensitization is associated with attenuation of the piperacillin-specific T-cell response.
•What is already known about this topic? Piperacillin-tazobactam exposure to patients with cystic fibrosis is associated with a high frequency of T-cell-mediated hypersensitivity reactions.•What does this article add to our knowledge? (1) The LTT is a sensitive/specific assay for the diagnosis of piperacillin hypersensitivity in patients with cystic fibrosis; (2) desensitization results in attenuation of the drug-specific T-cell response.•How does this study impact current management guidelines? In our hospital we currently use the LTT to confirm a diagnosis of piperacillin hypersensitivity. In the future it might be feasible to use the LTT (1) in tolerant patients before elective drug use and (2) allergic patients before drug (re)challenge or desensitization.