Cerebral phaeohyphomycosis due toRhinocladiella mackenziei(formerlyRamichloridium mackenziei): a taxonomic update and review of the literature

Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei (formerly Ramichlo-ridium mackenziei) is extremely rare, and geographically limited to the Middle East. The fungus exclusively targets the brain and infections have a grave prognosis. Eighteen cases have been reported in the literature from 1983 to 2004 with almost 100% mortality. Our patient presented in February 2008 with a brain abscess while receiving chemotherapy for carcinoma of the breast. Diagnosis was by craniotomy and aspiration of the brain abscess. Direct microscopy showed dematiaceous fungal hyphae. R. mackenziei was recovered in culture and this identification was confirmed by molecular analysis. Examination of histopathological sections of tissue from the brain biopsy revealed moniliform hyphae characteristic for phaeohyphomycosis. The patient failed to respond to antifungal therapy with amphotericin B and voriconazole or amphotericin B and posaconazole and finally expired 64 days after diagnosis. In vitro antifungal susceptibility testing showed this isolate to be resistant to amphotericin B while susceptible to itraconazole, voriconazole, and posaconazole. Previously published antifungal susceptibility data indicate that although strains show variable susceptibility to amphotericin B, the organism is generally refractory to treatment with this agent. Similar outcomes are seen with the azole agents used alone or in combination with other drugs. Although no specific risk factors have been identified, the majority of cases have occurred in immunocompromised individuals. R. mackenziei is a highly virulent agent of serious cerebral phaeohyphomycosis, and should be considered in the differential diagnosis of central nervous system disease in the Middle East.