Cerebral Aspergillus Infections and Meningitis

Abstract

Cerebral aspergillosis is notoriously difficult to treat and increasingly recognised in immunocompromised patients. These infections frequently result in brain abscess formation, but can also cause cerebral embolism or vasculitis, fungal aneurysms, cerebral granuloma or meningitis. Cerebral aspergillosis carries a particular poor prognosis with an almost 100% mortality in patients treated with either amphotericin B or itraconazole. Penetration of most available antifungal agents into the central nervous system (CNS) is largely limited by their molecular size, physicochemical properties or P-glycoprotein-mediated efflux at the blood-brain barrier. Voriconazole has a small molecular size (349 Da) favouring penetration into the CNS. Data from animal models and humans confirm that fungicidal concentrations of voriconazole may be attained not only in cerebrospinal fluid and brain tissue, but also in brain abscess material. In a retrospective study evaluating 81 patients with cerebral aspergillosis, voriconazole therapy was associated with an improved 35% response- and a 31% survival-rate. Neurosurgical interventions also had a positive impact on survival. Thus, voriconazole therapy and neurosurgical management, if considered feasible in individual patients, is currently the best approach to treat patients with cerebral aspergillosis. Animal model data indicate that higher drug doses or selected combination therapies could further enhance treatment efficacy, which should be explored in future studies to further improve the still unsatisfactory prognosis of cerebral aspergillosis.