Centre for Infectious Diseases and Tropical Medicine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Université de Paris, Paris, France.
Mycology Reference Centre Manchester and Department of Infectious Diseases, Manchester Academic Health Science Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Clin Infect Dis. 2024 Oct 15;79(4):936-943. doi: 10.1093/cid/ciae371.
Cerebral aspergillosis (CA) is associated with high mortality. According to the European Conference on Infections in Leukemia and the European Society of Clinical Microbiology and Infectious Diseases guidelines, the recommended first-line treatment for all forms of aspergillosis is voriconazole or isavuconazole. However, little is known about the efficacy and safety of isavuconazole in CA.
We conducted a European multicenter retrospective study of patients treated with isavuconazole for proven or probable CA between 2014 and 2022 and compared the outcomes with those of weighted control groups from the previously published French national cohort of CA, the Cerebral Aspergillosis Lesional Study (CEREALS).
Forty patients from 10 countries were included. The main underlying conditions were hematological malignancies (53%) and solid-organ transplantation (20%). Isavuconazole was administered as a first-line treatment to 10 patients, primarily in combination therapy, resulting in control of CA in 70% of these cases. Thirty patients received isavuconazole after a median of 65 days on another therapy, mostly because of side effects (50%) or therapeutic failure (23%) of the previous treatment. Predominantly given as monotherapy, it achieved control of CA in 73% of the patients. Seventeen patients (43%) underwent neurosurgery. When measured, isavuconazole levels were low in cerebrospinal fluid but adequate in serum and brain tissue. Isavuconazole toxicity led to treatment interruption in 7.5% of the patients. Twelve-week mortality was 18%. Comparison with the CEREALS cohort showed comparable survival in patients receiving isavuconazole or voriconazole as a first-line treatment.
Isavuconazole appears to be a well-tolerated treatment. Mortality of CA treated with isavuconazole is similar to that reported with voriconazole.
脑曲霉病（CA）与高死亡率相关。根据欧洲白血病感染会议和欧洲临床微生物学和传染病学会指南，所有形式曲霉病的一线推荐治疗药物是伏立康唑或伊曲康唑。然而，对于 CA 患者，伊曲康唑的疗效和安全性知之甚少。
我们进行了一项欧洲多中心回顾性研究，纳入了 2014 年至 2022 年期间使用伊曲康唑治疗确诊或疑似 CA 的患者，并将其结果与之前发表的法国 CA 全国队列（CEREALS）和脑曲霉病病变研究（CEREALS）的加权对照组进行了比较。
来自 10 个国家的 40 名患者被纳入研究。主要的基础疾病是血液系统恶性肿瘤（53%）和实体器官移植（20%）。10 名患者将伊曲康唑作为一线治疗药物，主要与联合治疗一起使用，其中 70%的患者的 CA 得到了控制。30 名患者在另一种治疗方案中位时间 65 天后开始使用伊曲康唑，主要是因为之前的治疗出现副作用（50%）或治疗失败（23%）。主要作为单药治疗，73%的患者 CA 得到了控制。17 名患者（43%）接受了神经外科手术。当测量时，伊曲康唑在脑脊液中的水平较低，但在血清和脑组织中是足够的。伊曲康唑毒性导致 7.5%的患者中断治疗。12 周死亡率为 18%。与 CEREALS 队列的比较显示，作为一线治疗药物，接受伊曲康唑或伏立康唑治疗的患者的生存率相似。
伊曲康唑似乎是一种耐受良好的治疗方法。用伊曲康唑治疗的 CA 的死亡率与用伏立康唑治疗的报道相似。
