University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
J Antimicrob Chemother. 2023 Aug 2;78(8):1813-1826. doi: 10.1093/jac/dkad143.
Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.
血液病患者（HM）发生侵袭性真菌病（IFD）的风险较高，发病率和死亡率较高。我们回顾了截至 2021 年 9 月发表的数据，以更新德国血液学和肿瘤医学学会（DGHO）的 2017 年抗真菌预防建议。对于持续中性粒细胞减少症（<500 个细胞/μL>7 天）的 HM 患者，强烈建议进行抗真菌预防，这一建议保持不变。泊沙康唑仍然是这些患者防霉活性预防的首选药物。考虑了 HM 中的新型治疗选择，例如 CAR-T 细胞治疗或急性髓细胞白血病（AML）的新型靶向治疗，但数据不足以对这些患者的常规抗真菌预防提供一般建议。与 2017 年版相比，特定建议的主要变化是现在对伊曲康唑和伏立康唑建议的支持从轻度改为中度。此外，关于米卡芬净的已发表证据允许以中度强度推荐其在 HM 中的使用。我们首次包括了关于 IFD 的非药物措施建议，包括使用高效微粒空气（HEPA）过滤器、吸烟、施工期间的措施和中性粒细胞减少饮食。我们回顾了三唑类抗真菌药物预防对通过细胞色素 p450 代谢的新型靶向治疗药物药物相互作用的影响，其中三唑类抑制 CYP3A4/5。工作组建议在与强 CYP3A4 抑制性抗真菌药物同时使用时减少 venetoclax 的剂量。此外，我们还回顾了新型抗真菌药物预防性使用的数据。目前没有证据支持在临床实践中预防性使用这些药物。
