In vitro activities of conventional and new antifungal drugs against Rhinocladiella mackenziei an agent of cerebral phaeohyphomycosis

Meis J.F., Badali H., de Hoog G.S., Breuker-Curfs I., Heep M.

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Background: The prevalence of cerebral phaeohyphomycosis caused by melanized fungi is rare but increasingly recognized in human disease. Rhinocladiella mackenziei is exclusively a central nervous system pathogen with 100% mortality and restricted to the Middle East and the Persian Gulf region. Limited in vitro and animal studies suggested that R. mackenziei is resistance to amphotericin B and presumably new antifungal drugs with broad-spectrum efficacy might be more effective. Therefore we have tested a total of 8 conventional and new antifungal drugs against 10 clinical isolates involved in this rare cerebral infection. Methods: A collection of 10 clinical isolates of R, mackenziei were obtained from the CBS Fungal Biodiversity Centre in Utrecht, The Netherlands. MICs were determined for amphotericin B (AmB), fluconazole (FLU), itraconazole (lTC), voriconazole (VOR), posaconazole (POS), isavuconazole (TSA) or MECs for caspofungin (CAS) and anidulafungin (ANI). Microdilution testing was done in accordance with CLSI M38-A2 guidelines adjusted spectrophotometrically at 530 nm wavelength to optical densities that ranged from 0.17-0.15 in RPMI 1640 MOPS broth with L-glutamine without bicarbonate and incubated at 35°C for 96 h. Results: R. mackenziei gave ranges, MI50 and MIC90 values for AmB, FLU, lTC, VOR, POS, ISA, CAS and ANI of 8, 32, 0.125, 1, 0.031, 0.5, 8, 2 and 16, 64, 0.25, 2, 0.063, 1, 8, 8 mg/ L, respectively. AmB, fluconazole and the two echinocandins had no activity against R. mackenziei. In contrast, POS, ITC, ISA and to a lesser extend VOR demonstrated in vitro activity against R. mackenziei. Conclusions: Our results are in line with animal data, demonstrating that ITC and POS had the highest in vitro antifungal activity against R. mackenziei. Isavuconazole seems to have also significant in vitro activity, Clinical effectiveness in the treatment of cerebral infection remains to be determined for these promising drugs.

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17th International Society for Human and Animal Mycology
    • ISHAM 17th (2009)