Prospective piperacillin lymphocyte transformation testing in patients with cystic fibrosis receiving regular and desensitization courses of piperacillin-tazobactam

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.