Prospective Piperacillin Lymphocyte Transformation Testing in Patients With Cystic Fibrosis Receiving Regular and Desensitization Courses of Piperacillin-Tazobactam.

Abstract

BACKGROUND: Piperacillin-tazobactam is used in patients with cystic fibrosis to treat recurrent respiratory infections. Exposure is associated with a high frequency of nonimmediate 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 1 was an analysis of LTT responses from 58 naive/baseline tolerant patients with samples collected over a 3-year interventional phase. In study arm 2, 17 hypersensitive patients were recruited and LTTs were conducted before and after desensitization. Clinical hypersensitivity reactions in both arms were monitored over an 8-year observational period. RESULTS: In study arm 1, 58 patients received 611 piperacillin-tazobactam courses (range, 2-40; mean +/- SD, 10.5 +/- 8.1) during the interventional phase; 11 patients developed hypersensitivity. The patients who remained tolerant received 236 piperacillin-tazobactam courses in the observational period, 9 of whom developed hypersensitivity. Ten of 11 interventional phase hypersensitive patients had a positive LTT whereas one remained negative. We recorded 136 negative LTTs with 39 tolerant patients, whereas eight patients had a positive LTT and four developed hypersensitivity during the observational period. Ten LTT-positive patients in study arm 2 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: The LTT is a sensitive marker of drug sensitization that could be used to inform future patient management. Desensitization is associated with attenuation of the piperacillin-specific T-cell response.