In vitro activities of antifungal drugs against Rhinocladiella mackenziei, an agent of fatal brain infection

Date

2009-10-23

Authors

Badali, Hamid
de Hoog, G. Sybren
Curfs-Breuker, Ilse
Meis, Jacques F.

Journal Title

Journal ISSN

Volume Title

Publisher

Oxford University Press

Abstract

Sir,

Cerebral phaeohyphomycosis is a rare disease with a mortality of up to 70% despite combinations of surgical and antifungal therapy. This infection is predominantly caused by Exophiala dermatitidis, Cladophialophora bantiana and Rhinocladiella mackenziei (order Chaetothyriales, family Herpotrichiellaceae), although organisms from other orders including Pleosporales, Sordariales, Xylariales and Helotiales can also cause infection. Rhinocladiella is a genus of black yeast-like fungi and can cause human infections ranging from mild cutaneous lesions to fatal brain infections. R. mackenziei (formerly Ramichloridium mackenziei) is an extremely neurotropic fungus, and infections that invade the CNS cause death in most instances. The infection is restricted largely to the Middle East, especially Saudi Arabia and Kuwait, although sporadic cases involving visitors or immigrants from endemic areas have been diagnosed in the UK and the USA. No clear epidemiological factors other than area of residence link these patients. Most R. mackenziei infections are brain abscesses in patients with no predisposing factors or immunodeficiency. Symptoms included headache, neurological deficits and seizures. Pathogenesis may be haematogenous from a subclinical pulmonary focus, although it remains unclear why this fungus preferentially causes CNS disease in immunocompetent individuals. Treatment regimens, which involve mostly amphotericin B, itraconazole and 5-flucytosine, are associated with a poor outcome in both animal and clinical studies. R. mackenziei demonstrates in vitro resistance to amphotericin B but susceptibility to triazoles such as itraconazole. Experimental R. mackenziei cerebral infection in mice indicates that posaconazole is superior to either amphotericin B or itraconazole for treatment of this condition.

Here we describe the in vitro activity of a new triazole antimycotic, isavuconazole, and seven comparators against 10 clinical isolates of R. mackenziei. [...]

Description

Keywords

cerebral fungal infection, in vitro susceptibility, Ramichloridium, isavuconazole, posaconazole

Citation

Badali, H., de Hoog, G. S., Curfs-Breuker, I., & Meis, J. F. (2009). In vitro activities of antifungal drugs against Rhinocladiella mackenziei, an agent of fatal brain infection. Journal of Antimicrobial Chemotherapy, 65(1), 175-177. doi:10.1093/jac/dkp390

Department

Molecular Microbiology and Immunology