Urbancic Karen F, Pisasale Daisy, Wight Joel, Trubiano Jason A
Pharmacy Department, Austin Health, Heidelberg, Victoria, Australia.
Infectious Diseases Department and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia.
Transpl Infect Dis. 2018 Dec;20(6):e12968. doi: 10.1111/tid.12968. Epub 2018 Aug 4.
Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.
对于接受免疫抑制治疗的血液学患者或造血干细胞移植（HSCT）后有甲氧苄啶 - 磺胺甲恶唑（TMP - SMX）药物不良反应（ADR）史的患者，氨苯砜可用于预防耶氏肺孢子菌肺炎（PJP）。氨苯砜引起的血液学毒性，如氧化性溶血，可能会限制其在这些患者中的使用，并且目前在非HIV的磺胺类药物过敏患者中，关于氨苯砜过敏交叉反应性的现代评估基本缺失。这项单中心回顾性研究的目的是描述在12个月期间，血液学患者（包括HSCT受者）中氨苯砜用于预防PJP的情况，包括适应证、氨苯砜所致氧化性溶血的发生率、既往有磺胺类药物过敏标记患者的免疫交叉反应性，以及描述重新引入一线TMP - SMX预防PJP的潜在机会。在符合研究纳入标准的24例患者中，12例（50%）在HSCT后接受氨苯砜预防PJP。未观察到突破性PJP感染病例。16例患者（67%）开始使用氨苯砜是为了避免TMP - SMX进一步骨髓抑制的风险，5例患者（21%）是因为先前对TMP - SMX有延迟的免疫介导过敏反应。氨苯砜治疗期间无一例出现皮疹。6例患者（25%）成功再次接受TMP - SMX治疗，其中1例患者既往有TMP - SMX相关皮疹。4例（17%）患者确诊为氧化性溶血，均导致停用氨苯砜。血液学患者使用氨苯砜预防PJP是有效且安全的，少数患者出现了无生命危险的氨苯砜相关溶血。未观察到磺胺类药物过敏交叉反应，这表明对于接受氨苯砜治疗的患者，可以考虑更多地再次使用TMP - SMX或进行脱敏治疗。
