There has been an increase in rare mould
infections in recent decades. These
infections have been reported primarily in severely immunocompromised patients. The emergence of these organisms is multifactorial and can be related to more intense immunosuppression, the prolonged survival of patients who have what were previously fatal diseases, and the selective pressure of broad spectrum
antifungal agents used for prophylaxis or
therapy. Among these rare mould
infections, the Zygomycetes are the most commonly encountered, and in some institutions the increase in these organisms appears to be associated with the use of
voriconazole. Aspergillus terreus, a species that is resistant to
amphotericin B, and less frequently, A. ustus and A. lentulus, have been noted increasingly as causes of invasive
aspergillosis in tertiary care centres in the US. Several species of Scedosporium with innate resistance to many
antifungal agents have emerged as major causes of disseminated mould
infections that are frequently very difficult to treat. Among patients who have haematological
malignancies, are neutropenic or have received a haematopoietic stem cell transplant,
infections due to Fusarium species respond poorly to many
antifungal agents. Dematiaceous, or brown-black, fungi, most often associated with chronic localised
infections, are now increasingly reported as a cause of disseminated
infection in immunosuppressed hosts. Concomitant with the increased number of
infections with these rare moulds, several new mould-active
antifungal agents have been developed. The new expanded spectrum
azole,
voriconazole, has changed our approach to moulds such as S.apiospermum, Fusarium species and A. terreus that are
amphotericin B resistant.
Posaconazole, the most recently approved expanded spectrum
azole, is the first
drug in the
azole class to show activity against the Zygomycetes and has proven extremely useful for step-down
therapy after initial treatment with
amphotericin B. It is not known whether
posaconazole is effective as primary
therapy for
zygomycosis; the use of this agent for that purpose awaits clinical trials with the recently developed intravenous formulation of
posaconazole.