In a prior study, we identified seven clinical isolates of an Aspergillus sp. that were slow to sporulate in multiple media and demonstrated decreased in vitro susceptibilities to multiple antifungals, including amphotericin B, itraconazole, voriconazole, and caspofungin. These isolates were initially considered to be variants of Aspergillus fumigatus because of differences in mitochondrial cytochrome b sequences and unique randomly amplified polymorphic DNA PCR patterns ( Phenotype studies revealed that the variant isolate has smaller conidial heads with diminutive vesicles compared to A. fumigatus and is not able to survive at 48°C. Our findings suggest the presence of a previously unrecognized, potentially drug-resistant Aspergillus species that we designate A. lentulus.

Invasive fungal infections caused by Neosartorya pseudofischeri S. W. Peterson [anamorph Aspergillus thermomutatus (Paden) S. W. Peterson] are extremely rare. Phenotypically, the anamorphic state of N. pseudofischeri resembles Aspergillus fumigatus, the predominant agent of invasive aspergillosis in immunocompromised hosts. We report the recovery of three clinical isolates of N. pseudofischeri, all initially misidentified by morphological characteristics as A. fumigatus. All three isolates were correctly identified by sequencing portions of the ␤-tubulin and the rodlet A genes. Only one of the three isolates produced the confirmatory fruiting bodies and was thus classified as N. pseudofischeri; the other isolates did not produce asci and were therefore identified as A. thermomutatus. All three isolates had higher MICs to voriconazole in vitro compared to A. fumigatus Af293. This report emphasizes that phenotypic identification of filamentous fungi may not identify morphologically similar, but genetically distinct, members of the genus Aspergillus section Fumigati. Accurate identification of these organisms may be clinically meaningful, given their potential differences in antifungal susceptibilities.Aspergillus fumigatus, the principal etiological agent of invasive aspergillosis, belongs to the genus Aspergillus section Fumigati and is identified in the laboratory predominantly by morphological features. Neosartorya fischeri and Neosartorya pseudofischeri also belong to section Fumigati, and their asexual (conidial) state closely overlaps that of A. fumigatus; thus, these two fungi appear morphologically very similar to A. fumigatus. Despite phenotypic similarity with A. fumigatus, N. fischeri and N. pseudofischeri have seldom been reported as etiologic agents of human aspergillosis. Phenotypically, Neosartorya fischeri (Wehmer, Malloch and Cain 1972) can be differentiated from the closely related N. pseudofischeri only by electron microscope analysis of the ascospore structure.To date there are only seven reported cases in which N. pseudofischeri has been recovered from invasive fungal infections (Table 1). The anamorphic (asexual) form of N. pseudofischeri, Aspergillus thermomutatus, grows as whitish, fast-growing, slowly sporulating colonies (producing conidiophores with conidia [sporulating] only after prolonged incubation on laboratory medium). Recently, several slowly sporulating Aspergillus isolates have been identified as members of a new species, Aspergillus lentulus (sp. nov. S. A. Balajee and K. A. Marr [1]). As part of a screening study to identify other A. lentulus isolates among culture collections in the United States, we recovered three poorly sporulating isolates that were phenotypically identified as A. fumigatus but were not A. lentulus by sequence typing of ␤-tubulin (benA) and rodlet A (rodA) gene regions. Data presented within demonstrate that these isolates are N. pseudofischeri and its anamorph, A. thermomutatus. MATERIALS AND METHODS Isolates. Isolate FH274 was received from the Fungus...

Candida glabrata, which can become resistant to fluconazole, is a common cause of bloodstream infection. This study was performed to determine the significance of cross-resistance to new azole drugs among C. glabrata isolates recovered as a cause of infection in azole-treated hematopoietic stem cell transplant (HSCT) recipients. Seven cases of invasive candidiasis caused by C. glabrata occurred in HSCT recipients who were receiving azole therapy between January 2000 and December 2004 in our institution. Case characteristics were ascertained. Sequential colonizing and invasive isolates were examined to determine susceptibilities to fluconazole, itraconazole, and voriconazole, and molecular relatedness by restriction fragment length polymorphism (RFLP) analysis. Twenty-three C. glabrata isolates were recovered from 4 patients who developed candidemia while receiving fluconazole and three patients who developed candidemia while receiving voriconazole. The mode MICs of fluconazole, itraconazole, and voriconazole for these isolates were >64 g/ml (range, 4 to >64 g/ml), 2 g/ml (range, 0.25 to >16 g/ml), and 1 g/ml (range, 0.03 to >16 g/ml), respectively. Kendall tau b correlation coefficients demonstrated significant associations between the MICs of voriconazole with fluconazole (P ‫؍‬ 0.005) and itraconazole (P ‫؍‬ 0.008). Colonizing and invasive isolates exhibiting variable susceptibilities had similar RFLP patterns. These observations suggest that C. glabrata exhibits considerable clinically significant cross-resistance between older azole drugs (fluconazole and itraconazole) and voriconazole.