Intracerebral infections due to filamentous fungi

S. Schwartz

Author address: 

Medizinische Klinik III, Charité Campus Benjamin Franklin, Berlin, Germany

Abstract: 

Invasive fungal infections are increasingly recognised as a major cause of morbidity and mortality in immunocompromised patients. Among various types of filamentous fungi Aspergillus has been most frequently recognised as a cause of invasive fungal infections, but infections caused by Zygomycetes, Fusarium or Scedosporium species have been increasingly reported in recent years. Infections caused by filamentous fungi are usually air-borne diseases resulting in pneumonia, sinusitis or less frequently in skin infections and are notoriously difficult to treat. From the initial sites of infection central nervous system (CNS) involvement might arise from extension of sinus/ear infections or hematogenous spread. Autopsy studies indicate that the CNS is the second most frequent organ affected in invasive aspergillosis. Typically, CNS-infections caused by filamentous fungi present as brain abscess, infarction or hemorrhage and less frequently as meningitis, mycotic aneurysm or granuloma formation. In immunocompromised patients, CNS-infections caused by filamentous fungi have a devastating prognosis and a fatality rate of almost 100% has been repeatedly reported in patient with neuroaspergillosis. The main contributory factor for this extremely poor prognosis is the limited penetration of most available antifungal drugs across the bloodbrain barrier. Treatment with standard doses of amphotericin B (deoxycholate or liposomal preparations), itraconazole and caspofungin result in negligible levels in the cerebrospinal fluid and brain tissue. However, high-dose liposomal amphotericin B (10 mg kg1) has been successfully used in few patients. Voriconazole, which is derived from fluconazole, has been repeatedly found in fungicidal concentrations in cerebrospinal fluid. Furthermore, high brain tissue concentrations of voriconazole have also been reported. No treatment guidelines for the management of CNS-infections caused by filamentous fungi are available, but a successful neurosurgical approach in addition to medical treatment has been repeatedly reported. In a recent retrospective analysis of 81 patients with proven or probable neuroaspergillosis, treatment with voriconazole resulted in an improved response rate of 35% and 31% of patients had a prolonged survival for a median observation time of 310 days. Interestingly, neurosurgery was significantly associated with an improved survival in this series of patients. In conclusion, CNS-infections caused by filamentous fungi are threatening conditions urgently requiring improved therapies. Antifungal drugs with improved penetration into the CNS should be preferentially used to treat these infections. Furthermore, a neurosurgical management should be considered whenever feasible, which might reduce the fungal burden and prevent complications (e.g. cerebral hemorrhage). Further studies using higher doses of medication or combination therapies and evaluating neurosurgical treatment approaches are clearly needed.
2005

abstract No: 

S09.4

Full conference title: 

2nd Trends in Medical Mycology
    • TIMM 2nd (2010)