School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
Pharmacy Department, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Transpl Infect Dis. 2022 Dec;24(6):e13988. doi: 10.1111/tid.13988. Epub 2022 Nov 15.
Limited consensus exists on the optimal use of antifungal agents to prevent invasive fungal infection in the early post allogeneic hematopoietic stem cell transplant (alloHCT) period, particularly when patients cannot tolerate oral medication administration.
We undertook a retrospective observational cohort study to assess the tolerability, efficacy, and cost of a new antifungal prophylaxis pathway at a major tertiary alloHCT centre. Patients aged ≥16 years who underwent alloHCT between February 2018 and October 2019 (cohort 1) or between April 2020 and November 2021 (cohort 2) were included. In both cohorts, first line prophylactic therapy was oral posaconazole. The second line drugs where oral therapy was unable to be administered were intravenous voriconazole (cohort 1) versus intravenous posaconazole (cohort 2).
There were 142 patients enrolled in the study, 71 in each cohort. The proportion of patients remaining on first-line prophylaxis or progressing to second-, third-, and fourth-line options was 22.5%, 39.4%, 29.6%, and 8.5% in cohort 1 and 39.4%, 59.2%, 1.4%, and 0% in cohort 2, respectively. The frequency of neuropsychiatric adverse events was significantly higher in cohort 1 compared to cohort 2 (49.3% vs. 19.8%, p = .0004). Occurrence of proven and probable fungal infections was not significantly different between cohorts. Antifungal drug expenditure was $359 935 (AUD) more in cohort 1 ($830 486 AUD) compared to cohort 2 ($477 149 AUD).
The antifungal prophylaxis pathway used in cohort 2 resulted in reduced antifungal-associated adverse effects, less patients requiring progression to 3rd and 4th line prophylaxis and reduced antifungal drug costs.
对于异体造血干细胞移植（alloHCT）后早期预防侵袭性真菌感染，目前对于抗真菌药物的最佳使用方法存在有限共识，尤其是当患者无法耐受口服药物治疗时。
我们进行了一项回顾性观察性队列研究，以评估主要的三级 alloHCT 中心新的抗真菌预防途径的耐受性、疗效和成本。纳入年龄≥16 岁，于 2018 年 2 月至 2019 年 10 月（队列 1）或 2020 年 4 月至 2021 年 11 月（队列 2）期间接受 alloHCT 的患者。在两个队列中，一线预防治疗药物均为口服泊沙康唑。如果不能口服治疗，则二线药物为静脉用伏立康唑（队列 1）或静脉用泊沙康唑（队列 2）。
本研究共纳入 142 例患者，每组 71 例。在队列 1 中，有 22.5%、39.4%、29.6%和 8.5%的患者继续接受一线预防治疗或进展至二线、三线和四线治疗方案，而在队列 2 中，这一比例分别为 39.4%、59.2%、1.4%和 0%。队列 1 中神经精神不良事件的发生率明显高于队列 2（49.3% vs. 19.8%，p=0.0004）。两组患者确诊和可能真菌感染的发生率无显著差异。与队列 2 相比，队列 1 中抗真菌药物支出高出 359935 美元（澳元）（830486 澳元）。
与队列 2 相比，队列 1 中使用的抗真菌预防途径导致抗真菌相关不良反应减少，需要进展到第 3 线和第 4 线预防治疗的患者减少，抗真菌药物成本降低。
