Evaluation of sulfonamide detoxification pathways in haematologic malignancy patients prior to intermittent trimethoprim-sulfamethoxazole prophylaxis

摘要: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Previously, it was reported that patients with haematologic malignancies on daily trimethoprim-sulfamethoxazole prophylaxis appeared to have a higher risk of sulfonamide hypersensitivity compared the general population. However, mechanisms for this apparent not been explored. WHAT STUDY ADDS • This paper provides first prospective evaluation antioxidant and reduction detoxification pathways in prior prophylaxis. • It also hypersensitivity, including development drug-specific T cells, started intermittent prophylaxis. • Our findings suggest defects metabolites are common malignancies, further, incidence skin rash cells appears be low intermittent, rather than daily, prophylaxis. AIMS Patients reportedly high sulfamethoxazole (SMX) hypersensitivity. The objective study determine whether deficiencies pathways, include glutathione (GSH) ascorbate (AA), cytochrome b5 (b5) reductase (b5R), were prevalent these patients. A secondary pilot drug following trimethoprim-SMX (TMP-SMX) approached dose regimens. METHODS Forty adult (HM) 35 healthy adults studied; an additional 13 HM taking supplements (HM-AA) evaluated. Twenty-two 40 prescribed compliant TMP-SMX 960 mg three four times weekly. RESULTS There no significant differences between groups plasma AA (median 37.2 µmvs. 33.9 µm) or red blood cell GSH (1.9 mmvs. 1.8 mm). correlated significantly leucocyte b5/b5R (r= 0.39, P= 0.002). Deficient activities found In fact, chronic lymphocytic leukaemia myeloma had median (80.7 µmol mg–1 min−1) controls (18.9 µmol mg–1 min−1, 0.008). After 3–4 weeks treatment, developed SMX-specific only one patient rash. CONCLUSIONS Deficiencies antioxidants population uncommon prophylaxis.