Treatment of cerebral aspergillosis with isavuconazole: an EFISG study

Introduction. Cerebral aspergillosis (CA) is associated with high mortality. According to ECIL-6 and 2018 ESCMID 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.

Methods. We conducted a European multi-centre retrospective study of patients treated with isavuconazole for proven or probable CA between 2014 and 2022 and compared the outcomes to those of weighted control groups from the previously published French national cohort of CA, the Cerebral Aspergillosis Lesional Study, which included 119 CA cases treated between 2006 -2018 (CEREALS).

Results. Forty patients from 10 countries were included. The main underlying conditions were hematological malignancies (53%) and solid organ transplantation (20%). Isavuconazole was given as a first-line treatment in 10 patients, mostly in combination therapy and led to control of the CA in 70% of the patients. Thirty patients received isavuconazole after 65 days of another therapy in median, mostly because of side-effects (50%) or therapeutic failure (23%) of the previous treatment. It led to control of the CA in 73% of the patient and was mostly given as monotherapy . Seventeen patients undergone 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 data from the CEREALS cohort showed a comparable survival in patients receiving isavuconazole or voriconazole as a first line treatment.

Conclusion. Isavuconazole appears to be a well-tolerated treatment. Mortality of CA treated with isavuconazole is similar to that reported with voriconazole.