Phaeohyphomycosis of the central nervous system (CNS) is a life-threatening
infection associated with severe morbidity. New approaches to treatment of CNS
phaeohyphomycosis are critically needed. We therefore studied
posaconazole with or without
caspofungin for treatment of experimental CNS
phaeohyphomycosis caused by Exserohilum rostratum. Each clinical isolate of E. rostratum isolate was inoculated intracisternally with 1.0 × 106 microconidia to fully anesthetized New Zealand White rabbits. Profound persistent
neutropenia and immunosuppression were established and maintained using
cytarabine and
methylprednisolone, respectively. Study groups consisted of
posaconazole suspension administered as oral formulation
at 10 (PSC10) or 20 (PSC20) mg/kg,
caspofungin (CFG) at 2 mg/kg intravenously (IV), combinations of PSC10+CFG or PSC20+CFG, and untreated controls (UC).
Posaconazole produced a significant reduction of residual fungal burden of E. rostratum in cerebrum, cerebellum, spinal cord, and paravertebral muscle (p < 0.01), in comparison to UC. The combination of PSC10+CFG and PSC20+CFG achieved full clearance of residual fungal burden from cerebrum, while only PSC20+CFG treated rabbits demonstrated clearance from cerebellum, spinal cord, and paravertebral muscle (p < 0.01). These data correlated with the significant reduction of CSF (1→3)-β-d-glucan levels in rabbits treated with PSC20 and PSC20+CFG in comparison to those of UC (p < 0.05).
Posaconazole alone or in combination with
caspofungin demonstrated significant antifungal efficacy in the treatment of experimental E. rostratum
meningoencephalitis and warrants further study for treatment of CNS
phaeohyphomycosis.