Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus.

The frequency of invasive mycoses due to opportunistic fungal pathogens has increased significantly over the past two decades (35, 74, 83, 88, 89, 101, 106). This increase in infections is associated with excessive morbidity and mortality (33, 50, 108) and is directly related to increasing patient populations at risk for the development of serious fungal infections, which includes individuals undergoing solid-organ transplantation, blood and marrow transplantation (BMT), and major surgery and those with AIDS, neoplastic disease, immunosuppressive therapy, advanced age, and premature birth (5, 35, 89, 106). Serious life-threatening infections are being reported with an ever increasing array of pathogens, including the wellknown opportunists Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus (35, 63, 88). New and emerging fungal pathogens include species of Candida and Aspergillus other than C. albicans and A. fumigatus: opportunistic yeastlike fungi such as Trichosporon spp., Rhodotorula spp., and Geotrichum capitatum (Blastoschizomyces capitatus); the zygomycetes; hyaline molds, such as Fusarium, Acremonium, Scedosporium, Paecilomyces, and Trichoderma species; and a wide variety of dematiaceous fungi (Table 1) (6, 57, 71, 83, 90, 94, 106, 113). The field of medical mycology has become an extremely challenging study of infections caused by a wide and taxonomically diverse array of opportunistic fungi. The message to both clinicians and clinical microbiologists is that there are no uniformly nonpathogenic fungi: any fungus can cause a lethal infection in a sufficiently immunocompromised host and should never be dismissed out of hand as a contaminant. Given the complexity of the patients at risk for infection and the diverse and increasing array of fungal pathogens, opportunistic mycoses pose considerable diagnostic and therapeutic challenges (79, 106). Diagnosis depends upon clinical suspicion and the retrieval of appropriate material for culture and histopathology. Isolation and identification of the infecting organisms are extremely important for the proper management of infections due to the less common opportunistic fungi (106). Some of these organisms are inherently nonsusceptible to standard azole or polyene therapy and may require the use of alternative antifungal agents, in addition to surgical management and reversal of the underlying impairment of host defenses (106). In this article we review selected emerging agents (e.g., C. glabrata) and less common agents of opportunistic mycoses with an emphasis on what is known of their susceptibility and resistance to both new and established antifungal agents. Although we now have available several exciting new antifungal agents with improved spectra of activity and potencies, it is useful to keep in mind that broad and injudicious use of any anti-infective agent in a severely immunocompromised host may result in superinfections due to organisms that are both unusual and drug resistant (94, 106).